專利名稱:脂環(huán)族磷脂酶a的制作方法
本涉及是1993年6月16日遞交的共同未決美國專利申請(qǐng)08/079,072的部分繼續(xù)申請(qǐng)。
本發(fā)明涉及的是具有磷脂酶A2(PLA2)抑制劑活性的化合物。PLA2是一種鈣依賴性酶,它切割磷脂的sn-2?;I,產(chǎn)生花生四烯酸和溶血磷脂(H.Van den Bosch et al.in Biochim.Biophys.Acta 1980,604,191)。這兩種反應(yīng)均可用作生物合成炎性介質(zhì)的起始點(diǎn)?;ㄉ南┧嵋坏┽尫?,即被環(huán)氧酶和脂氧酶等酶迅速代謝,產(chǎn)生熟知的發(fā)炎介質(zhì)前列腺素和白細(xì)胞三烯(leukotriene)(P.Davies and D.E.MacIntyre in"InflammationBasic Principles and Clinical Correlates",2nd Ed.,J.I.Callin,I.M.Goldstein and R.Snyderman,Eds,Raven Press,LtdNew York,1992;Chapter 7;B.K.Lam and K.F.Austen in "InflammationBasic Principles and Clinical Correlates",2nd Ed.J.I.Gallin,I.M.Goldstein,and R.Snyderman,Eds,Raven Press,LtdNew York,1992;Chapter 8)。溶血磷脂可被某些類型的細(xì)胞利用,產(chǎn)生血小板激活因子(PAF),即另一種有效的發(fā)炎介質(zhì)(G.A. Zimmerman,S.M.Prescott,and T.M McIntyre in"InflammationBasic Principles and Clinical Correlates",2nd Ed.J.I.Gallin,I.M.Goldstein,and R.Snyderman,Eds,Raven Press,LtdNew York,1992;Chapter 9)。PLA2在炎性疾病中的作用已有描述(P.Vadas and W.Pruzanski in Laboratory Investigation,1986,55,391-404;W.Pruzanski,E.Bogoch,M.Wloch,and P.Vadas in Journal of Rheumatology,1991,18,117-119;W.Pruzanski,K.Scott,G.Smith,I.Rajkovic,E.Stefanski,and P.Vadas in Inflammation,1992,16,451-457;W.Pruzanski,D.W.Wilmore,A.Suffredini,G.D.Martich,A.G.D.Hoffman,I.L.Browning,E.Stefanski,B.Sternby,and P.Vadas in Inflammation,1992,16,561-570;J.M.Gronroos and T.J.Nevalainen in Digestion,1992,52,232-236)。由于PLA2是導(dǎo)致前列腺素和白細(xì)胞三烯及PAF釋放途徑中的關(guān)鍵酶,因此抑制該酶也就成為預(yù)防、消除或改善炎癥的一種合適方法。
美國專利5,141,959公開了具有類似活性的化合物,該文獻(xiàn)并入本文以作參考。該專利公開了結(jié)構(gòu)式A化合物
其中Ra為CH=CY-C(CH3)=CHX,其中X和Y不同并選自COORb和 其中Rb和Rc各自獨(dú)立地為H或C1-6烷基。
本申請(qǐng)人已發(fā)現(xiàn)了式Ⅰ新化合物 其中C2和C3之間和/或C4和C5之間的連鍵不飽和;
X=COOH,H,F(xiàn),Cl,Br,I,COOR″,CONH2,COR′″,CHO,CH2OH,CH2OR′″,OH,OR′″,CF3,C1-6烷基,C1-6鏈烯基,C1-6鹵代烷基,NO2,P(O)(OH)2,SO2H,或SO3H;
R=取代或未取代烷基,芳基,芳烷基,鏈烯基,或芳基鏈烯基,條件是每一基團(tuán)有6個(gè)或多個(gè)碳原子(優(yōu)選6-30個(gè)碳原子),且R不為 R′=H或C1-6烷基;
R″=H,C1-6烷基,C(R3)2OC(O)R4,CH2CH2NR5R6,CH2CH2CH2NR5R6,CH2C(O)N(R6)2,或產(chǎn)生生理上可水解的酯的其它基團(tuán);
R′″=C1-6烷基;
R3=H,CH3,C2H5,CH3CH2CH2(R3相同或不同);
R4=C6-12芳基,C1-7直鏈、支鏈或環(huán)烷基,或C1-7直鏈、支鏈或環(huán)烷氧基;
R5=R6,或與R6連接為C3-C6環(huán)烷基,或-CH2CH2OCH2CH2-基團(tuán);
R6=C1-3烷基。
這些化合物、其幾何異構(gòu)體以及其藥用鹽顯示出PLA2抑制作用,具有顯著的消炎作用。
該新化合物及其異構(gòu)體和衍生物可與藥用載體和其它賦形劑結(jié)合,用于制備可優(yōu)選通過表皮或口服途徑給藥的配方。
本發(fā)明涉及新的化合物以及這些化合物、其異構(gòu)體或其可作藥用的衍生物在用于治療炎癥的方法及組合物中的應(yīng)用。
除非另外說明,這里所有的百分?jǐn)?shù)均是按組合物總重量計(jì)的重量百分?jǐn)?shù)。
本發(fā)明的化合物均符合式Ⅰ 其中C2和C3之間和/或C4和C5之間的鍵為不飽和鍵;
X=COOH,H,F(xiàn),Cl,Br,I,COOR″,CONH2,COR′″,CHO,CH2OH,CH2OR′″,OH,OR′″,CF3,C1-6烷基,C1-6鏈烯基,C1-6鹵代烷基,NO2,P(O)(OH)2,SO2H或SO3H;
R=取代或未取代烷基,芳基,芳烷基,鏈烯基或芳基鏈烯基,條件是每一基團(tuán)必須有6個(gè)或6個(gè)以上的碳原子(優(yōu)選6-30個(gè)碳原子),且R不為 R′=H或C1-6烷基;
R″=H,C1-6烷基,C(R3)2OC(O)R4,
CH2CH2NR5R6,CH2CH2CH2NR5R6,CH2C(O)N(R6)2,或產(chǎn)生生理上可水解的酯的其它基團(tuán)R′″=C1-6烷基;
R3=H,CH3,C2H5,CH3CH2CH2(各R3可相同或不同);
R4=C6-12芳基,C1-7直鏈、支鏈或環(huán)狀烷基,或C1-7直鏈、支鏈或環(huán)狀烷氧基;
R5=R6,或與R6連接為C3-6環(huán)烷基或-CH2CH2OCH2CH2-基團(tuán);
R6=C1-3烷基。
X優(yōu)選為H,COOH,F(xiàn),CF3,COOR″或CONH2。
在優(yōu)選實(shí)施方案中,C4位苯環(huán)上具有間位X取代基。R為所述取代或未取代基團(tuán)。當(dāng)R被取代時(shí),取代基可為OH、C1-12烷氧基、C1-12鏈烯氧基、C1-12環(huán)烷基、C1-12鹵代苯基烷氧基、C1-12羥烷基或金剛烷基。R可帶有1-6個(gè)取代基,該取代基為氫以外的基團(tuán)。優(yōu)選R為表1和2所列基團(tuán)。
對(duì)于“6個(gè)或更多個(gè)”碳原子,申請(qǐng)人意指6-30,優(yōu)選14-30個(gè)碳原子。
R′可為H或C1-6烷基,但優(yōu)選為H或CH3。
R″優(yōu)選為H。
“鹵素”意指Br、Cl、F或I。
當(dāng)R3、R5和R6為獨(dú)立基團(tuán)(即彼此不相連)時(shí),可相同或不同。
本發(fā)明化合物優(yōu)選符合下面的式IA、IB、IC或((具有試驗(yàn)化合物的CPM)-(本底))/((無試驗(yàn)化合物的CPM)-(本底)) )×100表1-6給出了IA至ID化合物的生物學(xué)活性。這些化合物是PLA2的有效抑制劑。
表1結(jié)構(gòu)11化合物(IA)的生物學(xué)數(shù)據(jù)
配方組合物或配方可含有一種或多種化合物本身。它們也可含有其異構(gòu)體和/或可作藥用的衍生物或類似物,如水合物,鹽(如琥珀酸鹽、乙酸鹽、鹽酸鹽、堿金屬鹽、銨鹽、季烷基銨鹽等)。金屬鹽的例子有鉀鹽和鈉鹽。銨鹽和季烷基銨鹽包括得自三乙醇胺、N-甲基葡糖胺、三(羥甲基)氨基甲烷和L-賴氨酸的鹽。
這類配方中活性成分或本發(fā)明化合物的濃度一般為約0.005-10.0wt%,優(yōu)選0.01-5wt%。
可使用載體、著色劑、香料、賦形劑、穩(wěn)定劑、流動(dòng)控制劑和其它可作藥用的賦形劑等添加劑。另外,也可包括一種或多種其它活性成分。
添加劑(本發(fā)明化合物以外的成分)的濃度一般為約90~99.995wt%。
給藥方法可給需要的對(duì)象服用本發(fā)明化合物、其異構(gòu)體及其可作藥用的衍生物或類似物,以治療炎癥,如牛皮癬、關(guān)節(jié)炎等。優(yōu)選的對(duì)象是人,但也可是小鼠或其它哺乳動(dòng)物。
上面所述的配方適合于經(jīng)鼻、靜脈、眼、頰、口腔或表皮等途徑給藥。優(yōu)選的途徑是跨皮,即表皮和口服給藥。
給藥的合適劑量形式包括丸劑、片劑、膠囊、液體組合物(可通過注射、食入或施用于皮膚表面或其它身體部位給藥)、油乳、凝膠、洗液、軟膏等。
實(shí)施例以下實(shí)施例舉例說明了符合式Ⅰ的各種化合物的制備方法。
在以下實(shí)施例中,所有溫度均為攝氏度,熔點(diǎn)在電熱裝置上測(cè)得且未校正。質(zhì)子和13C核磁共振(1H和13CNMR)譜記錄在Bruker AM-300或Varian Gemini 300分光計(jì)上。除非另外說明,所有光譜均在CDCl3、DMSO-d6、CD3CD或D2O中測(cè)得。化學(xué)位移以相對(duì)于四甲基甲硅烷(TMS)的單位表示,質(zhì)子間偶合常數(shù)以赫(HZ)表示。裂解方式以如下方式表示S,單峰;d,雙峰;t,三重峰;q,四重峰;m,多重峰;br,寬峰;dd,雙雙峰;dt,雙三重峰。紅外光譜在Perkin-Elmer 1800 FT-IR光譜計(jì)上從4000cm-1至400cm-1范圍內(nèi)測(cè)得,校準(zhǔn)至1601cm-1處聚苯乙烯膜的吸收,并以厘米倒數(shù)(cm-1)表示。質(zhì)譜是利用直接化學(xué)電離(DCI,異丁烯)或快速原子轟擊(FAB)在Kratos MS-50或Finnegan 4500裝置上記錄。紫外光譜是在Hewlett Packard 8452二極管排列光譜計(jì)在于所示溶劑中測(cè)得。
分析性薄層層析(TLC)在預(yù)覆硅膠板(60F-254)上進(jìn)行,并利用紫外線、碘蒸汽和/或通過與甲醇化磷銅酸一起加熱染色等方法顯色。柱層析(也稱為快速層析)是在使用細(xì)分硅膠的玻璃柱中進(jìn)行,并且是在約高于大氣壓下于所示溶劑中進(jìn)行。逆相分析性薄層層析是在預(yù)覆逆相板上進(jìn)行,并利用紫外線或碘蒸汽顯色。逆相柱層析是在使用Baker Octadecyl的玻璃柱(C18)(40μm)上進(jìn)行。
所有溶劑的蒸發(fā)均在減壓下完成。Celite是Johns-Manville Products Corporation公司為硅藻土登記的商標(biāo)。
實(shí)施例1合成化合物2的一般方法用于制備膦酸酯2的途徑是根據(jù)以下文獻(xiàn)Berry,J.P.;Isbell,A.F.;Hunt,G.E.J.Org.Chem.1972,37,4396。終產(chǎn)物通過在硅膠上進(jìn)行柱層析(10∶1的硅膠/粗化合物,用40%乙酸乙酯/己烷洗脫)或通過在0.1mmHg下蒸餾進(jìn)行純化。
對(duì)于2-(3-溴苯基)二乙基膦酰乙酸乙酯,量度=68.0mmol,通過層析純化,產(chǎn)率=79%;量度=120mmol,通過蒸餾純化(bp135-140℃,0.1mmHg),產(chǎn)率=75%;
1H NMR(300 MHz,CDCl3)δ7.67(d,J=2Hz,1H,ArH),7.44-7.48(m,2H,ArH),7.22(t,J=8Hz,1H,ArH),4.00-4.31(m,7H,CO2CH2,2×POCH2,and CH),1.21-1.36(m,9H,CO2CH2CH3and 2×POCH2CH3);13CNMR(75 MHz,CDCl3)δ166.50(d,J2c,p=4Hz,C=O),133.23,132.55(d,J3c,p=7Hz,ArC),131.10(d,J4c,p=3Hz,ArC),129.96,128.33(d,J3c,p=6Hz,ArC),122.36,63.56(d,J2c,p=7Hz,POC),63.29(d,J2c,p=7Hz,POC),62.06(CO2CH2),51.76(d,J1c,p=135Hz,CHP(0)),16.27(d,J3c,p=5Hz,POCH2CH3),and 14.04(CO2CH2CH3);IR(film)2985,2935,2910,1735(C=O),1595,1570,1475,1370,1320,1300,1260,1210,1150,1095,1050,1025,and 690cm-1;MS(DCI)m/e 379(MH+).
對(duì)于2-(3-氟甲基苯基)二乙基膦酰乙酸乙酯量度=34.3mmol,通過層析純化,產(chǎn)率=55%;量度=98.0mmol,通過蒸餾純化(bp 135-140℃,0.1mmHg),產(chǎn)率=69%;
1H NMR(300MHz,CDCl3)δ7.71-7.75(m,2H,ArH),7.55(d,J=8Hz,1H,ArH),7.45(t,J=8Hz,1H,ArH),3.97-4.42(m,7H,CO2CH2,2×POCH2,and CH),1.03-1.33(m,9H,CO2CH2CH3and 2×POCH2CH3);13CNMR(75MHz,CDCl3)δ167.07(d,J2c,p=4Hz,C=O),133.08(d,J3c,p=6Hz,ArC),132.17(d,J2c,f=8Hz),128.94,126.52(overlapping s and d,J3c,p=6Hz,2×ArC),124.76(d,J3c,f=3Hz,ArC),123.91(d,J1c,f=272Hz,CH3),63.54(d,J2c,p=7Hz,POC),63.27(d,J2c,p=7Hz,POC),62.10(CO2CH2),51.98(d,J1c,p=135Hz,CHP(O)),16.23(d,J3c,p=5Hz,POCH2CH3),16.16(d,J3c,p=5Hz,POCH2CH3),and 13.99(CO2CH2CH3);IR(film)2985,2935,2910,1740(C=O),1450,1395,1370,1330,1260,1210,1165,1125,1100,1080,1030,970,925,805,and 700 cm-1;MS(DCI)m/e369(MH+).
對(duì)于2-(3-氟苯基)二乙基膦酰乙酸乙酯量度=31.4mmol,通過層析純化,產(chǎn)率=69%;
1H NMR(300MHz,CDCl3)δ7.21-7.32(m,3H,ArH),6.95-7.01(m,1H,ArH),3.93-4.29(m,7H,CO2CH2,2×POCH2,and CH),0.98-1.33(m,9H,CO2CH2CH3and 2×POCH2CH3);13CNMR(75MHz,CDCl3)δ167.50(d,J2c,p=4Hz,C=O),162.58(d,J1c,f=245Hz,ArC),133.20(dd,J3c,p=8Hz,J3c,f=8Hz,ArC),129.83(d,J3c,f=8Hz),125.42(d,J3c,p=4Hz,ArC),116.69(dd,J2c,f=23Hz,J3c,p=6Hz,ArC),114.94(d,J2c,f=21Hz,ArC),63.50(d,J2c,p=7Hz,POC),63.20(d,J2c,p=7Hz,POC),61.99(CO2CH2),51.91(d,J1c,p=135Hz,CHP(O)),16.30(d,J3c,p=5Hz,POCH2CH3),16.23(d,J3c,p=5Hz,POCH2CH3),and 14.02(CO2CH2CH3);IR(film)2985,2935,2910,1735(C=O),1615,1590,1490,1450,1370,1320,1255,1155,1100,1050,1030,970,690,and 620cm-1;MS(DCI)m/e319(MH+).
對(duì)于2-(4-氟苯基)二乙基膦?;宜嵋阴チ慷龋?2.0mmol,通過層析純化,產(chǎn)率=85%;
1H NMR(300MHz,CDCl3)δ7.45-7.50(m,2H,ArH),7.01(apparentt,Jh,f=8.5Hz,Jh,h=8.5Hz,2H,ArH),3.88-4.25(m,7H,CO2CH2,2×POCH2,andCH),0.99-1.45(m,9H,CO2CH2CH3and2×POCH2CH3);13CNMR(75MHz,CDCl3)δ167.50(d,J2c,p=4Hz,C=O),162.55(d,J1c,f=245Hz,ArC),131.31(dd,J3c,p=8Hz,J3c,f=8Hz,ArC),126.74(d,J2c,p=6Hz),115.43(d,J2c,f=20Hz,ArC),63.40(d,J2c,p=7Hz,POC),63.12(d,J2c,p=7Hz,POC),61.91(CO2CH2),51.36(d,J1c,p=135Hz,CHP(O)),16.30(d,J3c,p=5Hz,POCH2CH3),16.23(d,J3c,p=5Hz,POCH2CH3),and 14.02(CO2CH2CH3);IR(film)2985,2935,2910,1735(C=O),1605,1510,1475,1445,1390,1370,1325,1300,1260,1225,1150,1100,1050,1030,970,900,850,815,795,and 740cm-1;MS(DCI)m/e319(MH+).
對(duì)于2-(苯基)二乙基膦酰乙酸乙酯量度=46.5mmol,通過層析純化,產(chǎn)率=85%;
1H NMR(300MHz,CDCl3)δ7.47-7.51(m,2H,ArH),7.25-7.35(m,3H,ArH),3.88-4.25(m,7H,CO2CH2,2×POCH2,and CH),1.14-1.26(m,9H,CO2CH2CH3and 2×POCH2CH3);13CNMR(75MHz,CDCl3)δ167.63(d,J2c,p=4Hz,C=O),130.95(d,J2c,p=8Hz,ArC),129.61(d,J3c,p=6Hz),128.48,127.91(d,J4c,p=3Hz,ArC),63.38(d,J2c,p=7Hz,POC),63.05(d,J2c,p=7Hz,POC),61.79(CO2CH2),52.26(d,J1c,p=135Hz,CHP(O)),16.29(d,J3c,p=5Hz,POCH2CH3),16.23(d,J3c,p=5Hz,POCH2CH3),and 14.03(CO2CH2CH3);IR(film)2985,2935,2910,1735(C=O),1500,1455,1390,1370,1300,1260,1210,1150,1095,1025,970,805,730,and 700cm-1;MS(DCI)m/e301(MH+).
實(shí)施例2方法A通過芳基齒的金屬轉(zhuǎn)移作用得到芳基醛在氬氣環(huán)境下將芳基齒(1當(dāng)量)的無水THF溶液(0.15-0.20M溶液)冷卻至-78℃,并用叔丁基鋰溶液(約1.6M于戊烷,2.0-2.1當(dāng)量)處理。于-78℃攪拌反應(yīng)混合物0.5-1h,然后用無水N,N-二甲基甲酰胺(2.0-3.0當(dāng)量)處理。溫?zé)岱磻?yīng)混合物至室溫,倒入含有乙醚和飽和氯化銨溶液的分液漏斗中。攪拌分層,用飽和氯化鈉溶液洗滌有機(jī)層,于無水硫酸鎂上干燥,過濾并濃縮。粗產(chǎn)物不經(jīng)純化直接使用,或者通過柱層析純化(20∶1的硅膠/粗產(chǎn)物;用1-10%于己烷的乙酸乙酯洗脫)。
對(duì)于5,6,7,8-四氫-5,5,8,8-四甲基-2-萘醛(3a)量度=10.2mmol,產(chǎn)率=95%。前體芳基齒5,6,7,8-四氫-5,5,8,8-四甲基-2-碘萘是通過W.W.Sy et al Synth.Commun.1990,20,877中的方法由5,6,7,8-四氫-5,5,8,8-四甲基萘(Maybridge Chemicals)制得。對(duì)于3a1H NMR(300MHz,CDCl3)δ9.92(s,1H,CHO),7.80(d,J=2Hz,1H,ArH),7.60(dd,J=2,8Hz,1H,ArH),7.44(d,J=8Hz,1H,ArH),1.69(brs,4H,CH2CH2),1.30(s,6H,2×CH3),and 1.29(s,6H,2×CH3);13CNMR(75MHz,CDCl3)δ192.38(C=O),152.43,145.92,134.16,128.61,127.41,126.60,34.93,34.73,34.68,34.41,31.75(CH3),and 31.59(CH3);IR(film)2960,2930,2860,1695(C=O),1600,1560,1460,1390,1365,1220,1210,1185,1170,1065,and 830cm-1;MS(DCI)m/e217(MH+).Anal.Calcd.for C15H20OC,83.29;H,9.32.FoundC,83.21;H,9.35.
對(duì)于5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽醛(3b)量度=6.60mmol,產(chǎn)率=77%。前體芳基齒5,6,7,8-四氫-5,5,8,8-四甲基-2-溴蒽是通過M.Dawson等人的方法(J.Labelled Compounds and Radiopharmaceuticals 1990,28,89)獲得。對(duì)于3b1H NMR(300MHz,CDCl3)δ10.09(s,1H,CHO),8.23(s,1H,ArH),7.93(s,1H,ArH),7.78-7.84(m,3H,ArH),1.77(br s,4H,CH2CH2),and 1.39(s,12H,4×CH3);13CNMR(75MHz,CDCl3)δ192.38(C=O),148.33,145.83,134.75,134.57,133.56,130.97,128.29,126.83,125.26,121.67,34.95,34.85,34.68,32.47(CH3),and32.40(CH3);IR(film)2955,2920,2860,1680(C=O),1630,1470,1460,1385,1365,1310,1165,1125,1110,910,895,and 810cm-1;MS(DCI)m/e267(MH+).Anal.Calcd for C19H22OC,84.96;H,8.27.FoundC,84.82;H,8.37.
對(duì)于4-(1-金剛烷基)-3-甲氧基苯甲醛(3c)量度=3.51mmol,產(chǎn)率=43%。前體芳基齒2-金剛烷基-5-碘茴香醚是通過以下方法分兩步得自3-碘苯酚。按照Shreet等人的美國專利4,717,720(1/1988)的一般方法用1-金剛烷醇和硫酸的二氯甲烷溶液處理3-碘苯酚。不經(jīng)重結(jié)晶,得到純的2-金剛烷基-5-碘苯酚量度=114mmol,產(chǎn)率=91%;mp142-144℃;
1H NMR(300MHz,DMSO-d6)δ7.08(d,J=2Hz,1H,ArH),7.04(dd,J=2,8Hz,1H,ArH),6.80(d,J=8Hz,1H,ArH),3.36(s,1H,OH),1.99(s,9H,adamantyl),and 1.68(s,6H,adamantyl);13CNMR(75MHz,CDCl3)δ157.26,135.66,128.32,127.54,124.50,91.23,39.61,36.56,36.12,and 28.32;IR(KBr)3480(OH),2900,2845,1490,1395,1210,and 875cm-1;MS(DCI)m/e 355(MH+),354(M+),353(M-H)+,135(C10H+15).Anal.Calcd for C16H19OIC,54.25;H,5.41.FoundC,54.32;H,5.37.
用硫酸二甲酯(4.11g,32.6mmol)和碳酸鉀(4.50g,32.6mmol)處理2-金剛烷基-5-碘苯酚(7.70g,21.7mmol)的丙酮(100ml)溶液?;亓鲾嚢璺磻?yīng)混合物24h,冷卻,并真空濃縮。粗產(chǎn)物在二氯甲烷和水之間分配。有機(jī)相于無水硫酸鎂上干燥,過濾,并濃縮,得到6.5g(81%)2-金剛烷基-5-碘茴香醚;
1H NMR(300MHz,CDCl3)δ7.22(dd,J=2,8Hz,1H,ArH),7.10(d,J=2Hz,1H,ArH),6.89(d,J=8Hz,1H,ArH),3.79(s,3H,OCH3),2.02(s,9H,adamantyl),and 1.73(s,6H,adamantyl);13CNMR(75MHz,CDCl3)δ159.35,138.43,129.63,128.25,120.75,91.20,55.22(OCH3),40.35,37.02,36.92,and 28.97;MS(DCI)m/e 369(MH+),368(M+),367(M-H)+,135(C10H+15).Anal.Calcd for C17H21OIC,55.45;H,5.75.FoundC,55.51;H,5.81.
按一般方法A使2-金剛烷基-5-碘茴香醚進(jìn)行反應(yīng),得到3c1H NMR(300MHz,CDCl3)δ9.92(s,1H,CHO),7.35-7.41(m,3H,ArH),3.88(s,3H,OCH3),2.08(s,9H,adamantyl),and 1.76(s,6H,adamantyl);13CNMR(75MHz,CDCl3)δ192.04(C=O),159.38,146.00,135.36,127.06,124.45,109.54,55.09(OCH3),40.15,37.79,36.95,and 28.90;IR(KBr)2965,2900,2850,1690(C=O),1250,1160,1135,1035,and 1025cm-1;MS(DCI)m/e271(MH+),135(C10H+15).Anal.Calcd for C18H22O2·0.02 H2OC,79.86;H,8.21.FoundC,79.48;H,8.34.
方法B通過用烷基鹵對(duì)羥基苯甲醛烷基化得到烷氧基芳基醛方法B-1于室溫及氬氣環(huán)境下,將氫化鈉(1.1-2.1當(dāng)量,80%于油中的分散液)用戊烷(3X)洗滌,并懸浮于無水二甲基亞砜(0.3-0.4M)溶液中。通過一套管加入羥基苯甲醛(1當(dāng)量)的DMSO溶液(0.2-0.25M終體積),并于室溫下攪拌該溶液1h。然后加入烷基鹵(1.2-2.0當(dāng)量),繼續(xù)攪拌混合物12-20h。倒入含有乙酸乙酯和飽和氯化銨溶液的分液漏斗中。攪拌分層,水層用乙酸乙酯萃取二次。合并后的有機(jī)相用鹽水洗滌,于無水MgSO4上干燥,過濾,并濃縮。殘余物通過柱層析在硅膠上純化(10∶1-20∶1,用己烷至5%-10%乙酸乙酯的己烷洗脫)。
方法B-2于室溫及氬氣條件下,用烷基鹵(2-4當(dāng)量)和碳酸鉀(2-4當(dāng)量)處理羥基苯甲醛(1當(dāng)量)的丙酮溶液(0.5M)。所得淤漿回流加熱14-20h,然后冷卻至室溫。混合物在乙醚和水之間分配。水層用乙醚萃取二次,合并的有機(jī)層用飽和氯化鈉溶液洗滌,于無水硫酸鈉上干燥,過濾,并濃縮。通過柱層析在硅膠上純化殘余物(10∶1-20∶1,用己烷至5%-10%乙酸乙酯的己烷洗脫)。
4-癸氧基苯甲醛(3d)為L(zhǎng)ancaster Chemicals公司的市售產(chǎn)品對(duì)于3-癸氧基苯甲醛(3e)通過方法B-1從3-羥基苯甲醛(Aldrich Chemicals)制得,量度=7.50mmol,產(chǎn)率=72%;
1HNMR(300MHz,CDCl3)δ9.95(s,1H,CHO),7.35-7.44(m,3H,ArH),7.11-7.18(m,1H,ArH),3.99(t,J=7Hz,2H,ArOCH2),1.78(quintet,J=7Hz,2H,ArOCH2CH2),1.20-1.50(m,14H,7×CH2),and 0.86(t,J=7Hz,3H,CH3);13CNMR(75MHz,CDCl3)δ192.23(C=O),159.71,137.57,129.97,123.28,121.97,112.75,68.31(ArOCH2),31.89,29.55,29.35,29.31,29.12,25.99,22.67,and 14.11;IR(film)2925,2855,2725,1700(C=O),1600,1585,1485,1450,1385,1285,and 1260cm-1;MS(DCI)m/e 263(MH+).
對(duì)于2-癸氧基苯甲醛(3f)通過方法B-1由2-羥基苯甲醛(Aldrich Chemicals)制得,量度=7.50mmol,產(chǎn)率=60%;
1H NMR(300MHz,CDCl3)δ10.49(s,1H,CHO),7.80(dd,J=2,8Hz,1H,ArH),7.50(dt,J=2,8Hz,1H,ArH),6.94-7.01(m,2H,ArH),4.05(t,J=7Hz,2H,ArOCH2),1.81(quintet,J=7Hz,2H,ArOCH2CH2),1.20-1.51(m,14H,7×CH2),and 0.85(t,J=7Hz,3H,CH3);13CNMR(75MHz,CDCl3)δ189.96(C=O),161.59,135.90,128.19,124.89,120.43,112.47,68.53(ArOCH2),31.87,29.54,29.32,29.30,29.08,26.05,22.67,and 14.11;IR(film)2925,2855,1690(C=O),1600,1585,1485,1460,1390,1300,1285,1240,1190,1160,and 755cm-1;MS(DCI)m/e 263(MH+).
對(duì)于4-[(2E),(6E)-3,7-二甲基-2,6-辛二烯氧基]苯甲醛(3g)通過方法B-1由4-羥基苯甲醛(Aldrich Chemicals)制得,量度=11.3mmol,產(chǎn)率=84%;
1H NMR(300MHz,CDCl3)δ9.85(s,1H,CHO),7.80(dt,J=2,8Hz,2H,ArH),6.98(dt,J=2,8Hz,2H,ArH),5.43-5.48(m,1H,C=CHCH2O),5.04-5.09(m,1H,CH=C(CH3)2),4.58(d,J=7Hz,2H,ArOCH2),2.00-2.15(m,4H,C=CHCH2CH2),1.73(s,3H,CH3),1.65(s,3H,CH3),and 1.58(s,3H,CH3);13CNMR(75MHz,CDCl3)δ190.79(C=O),164.00,142.13,131.94,129.80,123.62,118.59,114.98,65.24(ArOCH2),39.50,39.03,37.26,32.45,26.52,26.23,25.67,17.69,and 16.72;IR(film)2970,2925,2855,2735,1695(C=O),1600,1575,1510,1450,1430,1380,1310,1250,1160,1110,990,and 830cm-1;MS(DCI)m/e 259(MH+).
對(duì)于3,4-雙癸氧基苯甲醛(3h)通過方法B-2由3,4-二羥基苯甲醛(Aldrich Chemicals)制得,量度=72.4mmol,產(chǎn)率=53%;mp 59.5-60℃;UVmax(EtOH)310nm(ε=9,200),276nm(ε=11,000),232nm(ε=15,400);1H NMR(300MHz,CDCl3)δ9.81(s,1H,CHO),7.39(d,J=8Hz,1H,ArH),7.37(s,1H,ArH),6.93(d,J=8Hz,1H,ArH),4.05(t,J=7Hz,2H,ArOCH2),4.03(t,J=7Hz,2H,ArOCH2),1.77-1.88(m,4H,2×ArOCH2CH2),1.20-1.50(m,28H,14×CH2),and 0.86(t,J=7Hz,6H,2×CH3);13CNMR(75MHz,CDCl3)δ190.98(C=O),154.68,149.44,129.87,126.57,111.76,110.97,69.13(2×ArOCH2),31.90,29.57,29.34,29.07,28.98,25.97,25.94,and 14.10;IR(film)2955,2920,2850,1690(C=O),1675,1595,1585,1510,1470,1440,1395,1275,1235,1135,and 810cm-1;MS(DCI)m/e 419(MH+).Anal.Calcd for C27H46O3C,77.46;H,11.07.FoundC,77.19;H,10.99.
對(duì)于3,4-雙戊氧基苯甲醛(3i)通過方法B-2由3,4-二羥基苯甲醛(Aldrich Chemicals)制得,量度=109mmol,產(chǎn)率=定量;mp31-32.5℃;UVmax(EtOH)310nm(ε=9,000),276nm(ε=10,900),232nm(ε=15,500);1H NMR(300MHz,CDCl3)δ9.79(s,1H,CHO),7.38(dd,J=2,8Hz,1H,ArH),7.36(s,1H,ArH),6.91(d,J=8Hz,1H,ArH),4.04(t,J=7Hz,2H,ArOCH2),4.02(t,J=7Hz,2H,ArOCH2),1.77-1.88(m,4H,2×ArOCH2CH2),1.20-1.50(m,8H,4×CH2),and 0.90(t,J=7Hz,6H,2×CH3);13CNMR(75MHz,CDCl3)δ190.99(C=O),154.65,149.40,129.84,126.61,111.68,110.84,69.08(2×ArOCH2),28.74,28.65,28.16,28.12,22.42,and 14.02;IR(film)2955,2935,2860,1690(C=O),1675,1595,1585,1510,1465,1440,1395,1275,1240,1165,1135,1050,1025,1000,990,and 810cm-1;MS(DCI)m/e 279(MH+).Anal.Calcd for C17H26O3C,73.35;H,9.41.FoundC,73.61;H,9.40.
方法C通過用烯丙醇和乙酸鈀處理芳基碘制備3-芳基丙醛按照T.Jeffery J.Chem.Soc.,Chem.Commun.1984,1287所述的一般方法制備3-芳基丙醛。通過1H NMR對(duì)小等份試樣進(jìn)行分析測(cè)出所有芳基碘被消耗后,將反應(yīng)混合物在水和2∶1己烷/乙酸乙酯之間分配。水洗(5X)有機(jī)相,用無水硫酸鈉干燥,傾析,并濃縮,得到粗產(chǎn)物。
對(duì)于3-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-丙醛(3j)量度=27.6mmol,通過柱層析純化(40∶1硅膠/粗產(chǎn)物),產(chǎn)率=82%。按照W.W.Sy etal.Synth.Commun.1990,20,877的方法由5,6,7,8-四氫-5,5,8,8-四甲基萘(Maybridge Chemicals)制備前體芳基碘,即5,6,7,8-四氫-5,5,8,8-四甲基-2-碘萘。
1H NMR(300MHz,CDCl3)δ7.59(d,J=2Hz,1H,ArH),7.42(dd,J=2,8Hz,1H,ArH),7.03(d,J=8Hz,1H,ArH),1.65(s,4H,CH2CH2),1.25(s,6H,2×CH3),1.24(s,6H,2×CH3);13CNMR(75MHz,CDCl3)δ147.68,144.59,135.58,134.57,128.74,91.18,34.83,34.78,34.33,34.13,31.75,31.71;IR(KBr)2955,2920,2860,1580,1480,1455,1385,1360,1065,815cm-1;MS(DCI)m/e 315(MH+),314(M+),299(M-CH3)+.Anal.Calcd for C14H19IC,53.51;H,6.09;I,40.39,F(xiàn)oundC,53.82;H,6.08;I,40.33.For 3j1HNMR(300MHz,CDCl3)δ9.84(t,J=1.5Hz,1H,CHO),7.25(d,J=8Hz,1H,ArH),7.13(d,J=2Hz,1H,ArH),6.97(dd,J=2,8Hz,1H,ArH),2.89-2.95(m,2H,CH2),2.75-2.81(m,2H,CH2),1.69(s,4H,CH2CH2),and 1.29(s,12H,4×CH3);13CNMR(75MHz,CDCl3)δ201.83(C=O),144.94,142.73,137.02,126.63,126.19,125.40,45.18,35.02,34.96,34.10,33.87,31.77,and 27.77;IR(KBr)2960,2920,2855,1725(C=O),1455,1385,1360,and 820cm-1;MS(DCI)m/e245(MH+),227(M-OH)+.Anal.Calcd for C17H24OC,83.55;H,9.90.FoundC,83.85;H,9.93.
對(duì)于3-(3-(1-金剛烷基)-4-羥苯基)丙醛(3k)量度=28.2mmol,產(chǎn)率=98%。按照Shreet et al.U.S.Patent 4,717,720,1/1988所述一般方法,由4-碘苯酚和1-金剛烷醇制備前體芳基碘,2-金剛烷基-4-碘苯酚。量度=80mmol,產(chǎn)率=58%;
1H NMR(300MHz,CDCl3)δ7.44(d,J=2Hz,1H,ArH),7.32(dd,J=2,8Hz,1H,ArH),6.40(d,J=8Hz,1H,ArH),4.77(s,1H,OH),2.06(s,9H,adamantyl),and 1.75(s,6H,adamantyl);13CNMR(75MHz,CDCl3)δ154.18,139.13,136.05,135.32,118.87,83.53,40.16,36.73,36.80,and 28.80;IR(KBr)3530(OH),2910,2885,2850,1480,1390,1245,1120,820,and 805cm-1;MS(DCI)m/e 355(MH+),354(M+),135(C10H+15).Anal.Calcd for C16H19OIC,54.25;H,5.41,F(xiàn)oundC,54.46;H,5.44.
按照一般方法C反應(yīng)2-金剛烷基-4-碘苯酚產(chǎn)生3k1H NMR(300MHz,CDCl3)δ9.80(t,J=1Hz,1H,CHO),7.00(d,J=2Hz,1H,ArH),6.86(dd,J=2,8Hz,1H,ArH),6.56(d,J=8Hz,1H,ArH),4.71(s,1H,OH),2.86(t,J=7Hz,2H,CH2),2.73(t,J=7Hz,2H,CH2),2.08(br s,9H,adamantyl),and 1.75(s,6H,adamantyl);13CNMR(75MHz,CDCl3)δ202.19(C=O),152.83,136.51,132.17,127.04,126.23,116.82,45.65,40.50,37.02,36.64,29.00,and 27.69;IR(KBr)3340(OH),2910,2890,2850,1710,1510,1425,1370,and 1245cm-1;MS(DCI)m/e 285(MH+),284(M+),135(C10H+15).Anal.Calcd for C19H24O2·0.13 H2OC,79.59;H,8.53.FoundC,79.23;H,8.40.
對(duì)于3-(4-(1-金剛烷基)-3-羥苯基)丙醛(3l)量度=42.3mmol,通過柱層析純化(40∶1硅膠/粗產(chǎn)物;依次用二氯甲烷和5%甲醇/二氯甲烷洗脫),產(chǎn)率=44%。前體芳基碘2-金剛烷基-5-碘苯酚按實(shí)驗(yàn)3c所述方法由3-碘苯酚制得。對(duì)于3l
1H NMR(300MHz,DMSO-d6)δ9.67(s,1H,CHO),9.11(s,1H,OH),6.92(d,J=8Hz,1H,ArH),6.53-6.55(m,2H,ArH),2.68(s,4H,2×CH2),2.01(s,9H,adamantyl),and 1.68(s,6H,adamantyl);13CNMR(75MHz,CDCl3)δ202.88(C=O),155.91,138.85,133.25,126.05,118.57,116.18,44.23,39.96,36.66,35.84,28.41,and 26.87;IR(KBr)3445(OH),2910,2890,2845,1720(C=O),1430,and 1225cm-1;MS(DCI)m/e 285(MH+),284(M+),135(C10H+15).Anal.Calcd for C19H24O2·0.15 H2OC,79.49;H,8.53.FoundC,79.62;H,8.47.
對(duì)于3-[4-(1-金剛烷基)-3-叔丁基二甲基甲硅烷氧基苯基]丙醛(3m)量度=51.6mmol,通過柱層析純化(40∶1硅膠/粗品;用2∶1己烷/二氯甲烷洗脫),產(chǎn)率=70%。于60℃用叔丁基二甲基甲硅烷基氯處理2-金剛烷基-5-碘苯酚(制備見3c)制備出前體芳基碘2-金剛烷基-5-碘-1-(叔丁基二甲基甲硅烷氧基)苯。所用方法與Shreet等人的美國專利4,717,720,1/1988所述方法類似。通過柱層析純化(10∶1硅膠/粗品;用己烷洗脫),得到2-金剛烷基-5-碘-1-(叔丁基二甲基甲硅烷氧基)苯量度=118mmol,產(chǎn)率=97%;
1H NMR(300MHz,CDCl3)δ7.19(dd,J=2,8Hz,1H,ArH),7.09(d,J=2Hz,1H,ArH),6.90(d,J=8Hz,1H,ArH),2.04(s,9H,adamantyl),1.74(s,6H,adamantyl),1.03(s,9H,SiC(CH3)3),and 0.34(s,6H,Si(CH3)2);13CNMR(75MHz,CDCl3)δ155.39,139.48,129.58,128.80,127.86,90.43,40.18,36.97,36.78,28.92,26.39(SiC(CH3)3),19.00(SiC(CH3)3),and-3.51(Si(CH3)2);IR(film)2930,2910,2875,2855,2845,1575,1480,1390,1265,1250,1240,930,850,800,and 785cm-1;MS(DCI)m/e 469(MH+),135(C10H+15).Anal.Calcd for C22H33OISiC,56.40;H,7.10,F(xiàn)oundC,56.66;H,7.25.
按照一般方法C反應(yīng)2-金剛烷基-5-碘-1-(叔-丁基二甲基甲硅烷氧基)苯,得到3m1H NMR(300MHz,CDCl3)δ9.81(s,1H,CHO),7.11(d,J=8Hz,1H,ArH),6.70(dd,J=2,8Hz,2H,ArH),6.61(d,J=2Hz,1H,ArH),2.83-2.89(m,2H,CH2),2.71-2.76(m,2H,CH2),2.06(s,9H,adamantyl),1.74(s,6H,adamantyl),1.03(s,9H,SiC(CH3)3),and 0.33(s,6H,Si(CH3)2);13CNMR(75MHz,CDCl3)δ201.77(C=O),154.71,138.46,137.53,127.18,120.14,119.05,45.03,40.43,37.05,36.56,29.02,27.42,26.43(SiC(CH3)3),18.96(SiC(CH3)3),and-3.34(Si(CH3)2);IR(KBr)2955,2930,2910,2850,1720(C=O),1415,1250,990,855,and 780cm-1;MS(DCI)m/e 399(MH+),398(M+),135(C10H15+).Anal.Calcd for C25H38O2SiC,75.32;H,9.61.FoundC,75.62;H,9.66.
對(duì)于3-[2-(1-金剛烷基)-4-甲氧苯基]丙醛(3n)按下面的5步驟制得。在氮?dú)猸h(huán)境下用粉化碳酸鉀(1.06g,7.70mmol)和硫酸二甲酯(0.97g,7.70mmol)處理2-(1-金剛烷基)-1,4-氫醌(Miryan,N.I.;et al Ukr.Khim.Zh.(Russ Ed.)1990,56,183)(1.88g,7.70mmol)的丙酮(100ml)溶液?;亓鲾嚢?8h后,冷卻反應(yīng)混合物并真空濃縮。殘余物在乙醚和飽和氯化銨溶液之間分配。有機(jī)相用水(5X)和鹽水洗滌,用硫酸鎂干燥,用活性炭處理,通過硅藻土過濾,真空濃縮后得到一油狀物。通過柱層析純化(20∶1硅膠/粗品;用二氯甲烷洗脫)后得到1.0g灰白色固體。用乙醚研磨后得到0.93g(47%)2-(1-金剛烷基)4-甲氧基苯酚白色固體。
1H NMR(300MHz,CDCl3)δ8.75(s,1H,OH),6.64(d,J=8.5Hz,1H,ArH),6.59(d,J=3Hz,1H,ArH),6.55(dd,J=3,8.5Hz,1H,ArH),3.62(s,3H,OCH3),2.00-2.03(m,9H,adamantyl),and 1.70(s,6H,adamantyl);13CNMR(300MHz,CDCl3)δ151.98,149.81,136.51,116.49,112.75,110.50,55.14(OCH3),39.72,36.61,36.17,and 28.39;IR(KBr)3380,2930,2910,2885,2850,1500,1420,1210,1030,and 745cm-1;MS(DCI)m/e 259(MH+),258(M+),257(MH)+,135(C10H+15).Anal.Calcd for C17H22O2C,79.03;H,8.58.FoundC,78.91;H,8.51.
將2-(1-金剛烷基)-4-甲氧基苯酚(0.93g,3.60mmol)的二氯甲烷(60ml)淤漿冷卻至-78℃,用乙基二異丙胺(0.51g,3.96mmol)處理。將三氟甲磺酸酐(1.12g,3.96mmol)滴加至攪拌溶液中。加畢,將反應(yīng)混合物于0℃攪拌5h,并于室溫?cái)嚢?8h。真空除去溶劑,并將殘余物在乙酸乙酯和水之間分配。水洗(5x)有機(jī)相,用無水硫酸鎂干燥,過濾,并濃縮,得到1.36g(96%)2-(1-金剛烷基)-4-甲氧基苯氧基三氟甲磺酸酯。
1H NMR(300MHz,CDCl3)δ7.22(d,J=9Hz,1H,ArH),6.92(d,J=3Hz,1H,ArH),6.71(dd,J=3,9Hz,1H,ArH),3.79(s,3H,OCH3),2.09(s,3H,adamantyl);2.02-2.03(m,6H,adamantyl),and 1.74-1.76(m,6H,adamantyl);13CNMR(300MHz,CDCl3)δ158.34,143.10,142.88,122.11,118.36(q,J1c,f=318Hz,CF3),115.04,110.84,55.56(OCH3),40.89,37.13,36.50,and 28.80;IR(KBr)2910,2855,1580,1480,1415,1270,1245,1220,1210,1195,1140,1035,920,890,865,800,and 580cm-1;MS(DCI)m/e 391(MH+),390(M+),389(MH)+,255(M-C10H15+2H)+,135(C10H+15).Anal.Calcd for C18H21O4SF3C,55.38;H,5.42.FoundC,55.48;H,5.41.
按照A Echavarren and J.K.Stille J.Am.Chem.Soc.1987,109,5478所述的一般方法,將2-(1-金剛烷基)-4-甲氧基苯氧基三氟甲磺酸酯(1.51g,3.87mmol)、3-三丁基甲錫烷基-(2E)丙烯醇(1.48g,4.25mmol)(Jang,M.E.;Light,L.A.Tetrahedron Lett.1982,23,3851)和聯(lián)三苯膦二氯化鈀(0.05g,0.08mmol)的二甲基甲酰胺溶液于90℃加熱16h。通過柱層析純化(25∶1硅膠/粗產(chǎn)物;用20%乙酸乙酯/己烷洗脫)得到0.99g(86%)3-[2-(1-金剛烷基)-4-甲氧苯基]-(2E)-丙烯醇。
1H NMR(300MHz,CDCl3)δ7.35(d,J=15Hz,1H,ArCH=CH),7.30(d,J=8.5Hz,1H,ArH),6.89(d,J=3Hz,1H,ArH),6.68(dd,J=3,8.5Hz,1H,ArH),5.93(dt,J=15,6Hz,1H,ArCH=CH),3.79(s,3H,OCH3),2.06-2.08(m,9H,adamantyl),and 1.75(s,6H,adamantyl);13CNMR(300MHz,CDCl3)δ159.19,149.10,132.98,130.76,129.28,127.76,112.94,109.80,64.19(OCH2),55.15(OCH3),41.89,37.95,36.84,and 29.09;IR(KBr)3345(OH),2905,2850,1600,1570,1475,1450,1300,1260,1235,1030,and 760cm-1;MS(DCI)m/e 299(MH+),298(M+),281(M-OH)+,135(C10H15+).Anal.Calcd for C20H26O2C,80.50;H,8.78.FoundC,80.43;H,8.87.
利用催化的10%披鈀炭于60psi在乙醇中氫化3-[2-(1-金剛烷基)-4-甲氧苯基]-(2E)-丙烯醇(0.99g,3.30mmol)。48h后,通過硅藻土過濾溶液并真空濃縮,得到粗品。通過柱層析純化(20∶1硅膠/粗品;用二氯甲烷洗脫),得到3-[2-(1-金剛烷基)-4-甲氧基苯基]-丙醇(0.74g,75%)。
1H NMR(300MHz,CDCl3)δ7.09(d,J=8.5Hz,1H,ArH),6.87(d,J=3Hz,1H,ArH),6.69(dd,J=3,8.5Hz,1H,ArH),3.73-3.77(m,5H,OCH2and OCH3),2.92-2.97(m,2H,ArCH2),2.04-2.09(m,9H,adamantyl),1.81-1.91(m,2H,ArCH2CH2),and 1.75-1.77(s,6H,adamantyl);13CNMR(300MHz,CDCl3)δ157.43,149.02,132.74,132.69,113.02,109.98,63.04(OCH2),55.11(OCH3),42.10,37.93,36.85,36.39,29.91,and 29.19;IR(KBr)3355(OH),2905,2850,1605,1575,1450,1290,1255,1235,1055,1035,and 755cm-1;MS(DCI)m/e 301(MH+),300(M+),299(M-H)+,165(M-C10H15)+,135(C10H+15).Anal.Calcd for C20H28O2C,79.96;H,9.39.FoundC,79.63;H,9.52.
按W.Griffith and S.Ley Aldrichimica Acta 1990,23,13所述一般方法,利用催化劑過釘酸四丙基銨氧化3-[2-(1-金剛烷基)-4-甲氧苯基]-丙醇(0.62g,2.1mmol)。經(jīng)柱層析純化(40∶1硅膠/粗品;用乙酸乙酯/己烷洗脫),得到3-[2-(1-金剛烷基)-4-甲氧苯基]丙醛(3n)(0.42g,68%)。
1H NMR(300MHz,CDCl3)δ9.87(s,1H,CHO),7.04(d,J=8Hz,1H,ArH),6.90(d,J=3Hz,1H,ArH),6.71(dd,J=3,8Hz,1H,ArH),3.79(s,3H,OCH3),3.22(m,2H,CH2),2.77(m,2H,CH2),2.10(s,3H,adamantyl),2.03(m,6H,adamantyl),and 1.77(s,6H,adamantyl).
實(shí)施例3合成化合物4的一般方法于室溫及氬氣條件下,通過滴加乙醇鈉的乙醇溶液(21wt%,1.1-1.5當(dāng)量),處理膦酸酯2(1.2-1.6當(dāng)量)和醛3(1當(dāng)量)的溶液。于室溫-70℃攪拌反應(yīng)混合物4-14h。然后將混合物在乙醚和飽和氯化銨溶液之間分配,有機(jī)層進(jìn)一步用飽和氯化鈉溶液洗滌,于無水硫酸鎂上干燥,過濾,并濃縮。粗品通過柱層析純化(40∶1硅膠/粗品;用2-3%乙酸乙酯的己烷洗脫)。
對(duì)于(E)-2-(3-溴苯基)-3-苯基-丙烯酸乙酯(4a)量度=2.46mmle,產(chǎn)率=87%1H NMR(300MHz,CDCl3)δ7.83(s,1H,C=CH from(E)-isomer),7.62(t,J=2Hz,1H,2-ArH),7.13-7.48(m,9H,ArH and C=CH from (Z)-isomer),4.25(q,J=7Hz,2H,CO2CH2),1.28(t,J=7Hz,3H,CO2CH2CH3from(E)-isomer),and 1.17(t,J=7Hz,3H,CO2CH2CH3from (Z)-isomer);13CNMR(75MHz,CDCl3)δ167.21(C=O),140.89,138.01,134.15,132.70,131.18,130.85,130.56,130.07,129.45,129.30,128.58,128.46,128.31,125.12,122.41,61.50(CO2CH2from(Z)-isomer),61.35(CO2CH2from(E)-isomer),14.24(CO2CH2CH3from(E)-isomer),and 13.81(CO2CH2CH3from (Z)-isomer);IR(film)2980,1710(C=O),1560,1475,1450,1370,1245,1210,1180,1075,1040,and690cm-1;MS(DCI)m/e 331/333(MH+,1∶1).
對(duì)于(E)-2-(3-溴苯基)-3-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-甲烯酸乙酯(4b)量度=8.63mmol,產(chǎn)率=63%;
UVmax(CH3OH)300nm(ε=19.900);1H NMR(300MHz,CDCl3)δ7.77(s,1H,C=CH),7.47(dt,J=2,8Hz,1H,2-ArH),7.38(t,J=2Hz,1H,2-ArH),7.13-7.28(m,3H,ArH),6.92(d,J=2Hz,1H,3-ArH),6.87(dd,J=2,8Hz,1H,3-ArH),4.23(q,J=7Hz,2H,CO2CH2),1.57(brs,4H,CH2CH2),1.27(t,J=7Hz,3H,CO2CH2CH3),1.20(s,6H,2×CH3)and 0.98(s,6H,2×CH3);13CNMR(75MHz,CDCl3)δ167.45(C=O),146.94,144.85,141.23,138.82,132.67,131.12,130.68,130.25,129.85,129.11,128.60,128.41,126.64,122.61,61.22(CO2CH2),34.79(CH2CH2),34.32,33.96,31.56(CH3),31.42(CH3),and 14.29(CO2CH2CH3);IR(film)2960,2930,2860,1710(C=O),1620,1605,1560,1490,1470,1460,1365,1280,1245,1215,1175,1070,1040,and 830cm-1;MS(DCI)m/e 441/443(MH+,1∶1).
對(duì)于(E)-2-(3-溴苯基)-3-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-丙烯酸乙酯(4c)量度=5.0mmol,產(chǎn)率=64%;
1H NMR(300MHz,CDCl3)δ8.00(s,1H,3-ArH),7.66(s,3H,3-ArH and C=CH),7.41-7.51(m,3H,ArH),7.15-7.21(m,2H,ArH),6.81(dd,J=1,9Hz,1H,ArH),4.29(q,J=6Hz,2H,CO2CH2),1.75(s,4H,CH2CH2),and 1.27-1.41(m,15H,4×CH3and CO2CH2CH3);13CNMR(75MHz,CDCl3)δ167.43(C=O),146.14,145.06,141.49,138.27,133.04,131.81,131.56,131.39,131.05,130.85,130.52,130.00,128.96,126.94,125.64,125.60,124.76,122.40,61.32(CO2CH2),34.97(CH2CH2),34.72,34.58,32.47 and 32.44(4×CH3),and 14.32(CO2CH2CH3);IR(film)2960,2930,1710(C=O),1615,1470,1365,1240,1185,1165,and 1150cm-1;MS(DCI)m/e 493/491(MH+,1∶1).
對(duì)于(E)-2-(3-溴苯基)-3-(4-癸氧苯基)丙烯酸乙酯(4d)量度=9.60mmol,產(chǎn)率=79%;
1H NMR(300MHz,CDCl3)δ7.77(s,1H,C=CH),7.36-7.48(m,2H,2-ArH),7.11-7.25(m,2H,2-ArH),6.96(d,J=8Hz,2H,3-ArH),6.67(d,J=8Hz,2H,3-ArH),4.22(q,J=7Hz,2H,CO2CH2),3.88(t,J=7Hz,2H,ArOCH2),1.71(quintet,J=7Hz,2H,ArOCH2CH2),1.21-1.43(m,17H,7×CH2and CO2CH2CH3),and 0.85(t,J=7Hz,3H,CH3);13CNMR(75MHz,CDCl3)δ167.52(C=O),160.12,140.72,138.59,132.79,132.43,130.70,130.17,128.67,128.50,126.46,122.50,114.32,68.01(ArOCH2),61.16(CO2CH2),31.88,29.54,29.34,29.11,25.96,22.67,14.29,and 14.12;IR(film)2925,2855,1710(C=O),1600,1570,1560;1510,1470,1365,1300,1250,1210,1170,1070,1040,830,and 690cm-1;MS(DCI)m/e 487/489(MH+,1∶1).
對(duì)于(E)-2-(3-溴苯基)-3-(3,4-二癸氧基苯基)-丙烯酸乙酯(4e)量度=3.2mmol,產(chǎn)率=46%;
1H NMR(300MHz,CDCl3)δ7.75(s,1H,C=CH),7.45(dd,J=2,6Hz,1H,2-ArH),7.41(t,J=1Hz,1H,2-ArH),7.25(t,J=8Hz,1H,2-ArH),7.16(dt,J=1,8Hz,1H,2-ArH),6.77(dd,J=2,8Hz,1H,3-ArH),6.70(d,J=8,1H,3-ArH),6.40(d,J=2Hz,1H,3-ArH),4.23(q,J=7Hz,2H,CO2CH2),3.94(t,J=7Hz,2H,ArC4OCH2),3.48(t,J=7Hz,2H,ArC3OCH2),1.71-1.78(m,2H,ArC4OCH2CH2),1.60-1.65(m,2H,ArC3OCH2CH2),1.17-1.29(m,31H,CO2CH2CH3and 14×CH2),and 0.83-0.87(m,6H,2×CH3);13CNMR(75MHz,CDCl3)δ167.46(C=O),150.34(3-ArC4),148.20(3-ArC3),141.00,138.90,132.89,130.59,130.24,128.76,128.31,126.65,125.64,114.15,112.29,68.87(ArOCH2),68.46(ArOCH2),61.14(CO2CH2),31.92,31.89,29.63,29.57,29.54,29.37,29.34,29.03,28.94,25.93,25.83,22.69,22.67,14.29,and 14.13;IR(KBr)2955,2920,2850,1705(C=O),1515,1465,1275,1250,1225,1190,and 1140cm-1;MS(DCI)m/e 645/643(MH+,1∶1).
對(duì)于(E)-2-(3-溴苯基)-5-苯基-2-丙烯酸乙酯(4f)量度=7.91mmol,產(chǎn)率=48%;
1H NMR(300MHz,CDCl3)δ7.42(dt,J=2,8Hz,1H,2-ArH),7.06-7.28(m,8H,3×2-ArH,4×5-ArH,and C=CH),6.91(dt,J=2,8Hz,1H,5-ArH),4.18(q,J=7Hz,2H,CO2CH2),2.72(t,J=8Hz,2H,ArCH2),2.37(q,J=8Hz,2H,ArCH2CH2),and 1.24(t,J=7Hz,3H,CO2CH2CH3);13CNMR(75MHz,CDCl3)δ166.44(C=O),144.41,140.54,137.21,133.54,130.43,129.40,128.34,126.20,121.80,60.93(CO2CH2),34.81,31.36,and 14.14(CO2CH2CH3);IR(film)3060,3025,2980,2935,2860,1710(C=O),1560,1475,1455,1365,1260,1250,1185,1070,1045,790,750,and 700cm-1;MS(DCI)m/e 359/361(MH+,1∶1).
對(duì)于(E)-2-(3-溴苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-戊烯酸乙酯(4g)量度=14.7mmol,產(chǎn)率=64%;
1H NMR(300MHz,CDCl3)δ7.40-7.44(m,1H,2-ArH),7.10-7.26(m,4H,3×2-ArH and C=CH),7.04(s,1H,5-ArH),6.82-6.89(m,2H,5-ArH),4.21(q,J=7Hz,2H,CO2CH2),2.71(t,2H,J=8Hz,ArCH2),2.37(q,J=8Hz,2H,ArCH2CH2);1.69(m,4H,CH2CH2),and 1.23-1.33(m,15H,4×CH3and CO2CH2CH3);13CNMR(75MHz,CDCl3)δ166.58(C=O),154.95,144.90,144.78,142.73,137.49,137.37,133.26,132.55,130.45,60.99(CO2CH2),35.18,35.14,34.72,34.20,34.01,31.96,31.88,31.62,and 14.29(CO2CH2CH3);IR(film)2960,2925,2860,1715(C=O),and 1250cm-1;MS(DCI)m/e 469(MH+);Exact mass spectrum(FAB)Calcd for C27H33BrO2(MH+)469.1742.Found469.1745.
對(duì)于(2E),(4E)-2-(3-溴苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘)-2,4-己二烯酸乙酯(4h)量度=8.19mmol,產(chǎn)率=45%;
1H NMR(300MHz,CDCl3)δ7.91(d,J=12Hz,1H,C=CH),7.42-7.46(m,2H,2-ArH),7.16-7.29(m,4H,ArH),7.10(dd,J=2,8Hz,1H,5-ArH),6.43(dd,J=1.5,12Hz,1H,C=CH),4.25(q,J=7Hz,2H,CO2CH2),2.27(d,J=1.5Hz,3H,C=CCH3),1.64(br s,4H,CH2CH2),1.27(t,J=7Hz,3H,CO2CH2CH3),and 1.23(s,12H,4×CH3);13CNMR(75MHz,CDCl3)δ167.27(C=O),148.20,146.20,145.00,139.00,137.14,133.32,130.50,129.36,129.16,126.64,124.21,123.32,122.05,61.01(CO2CH2),35.03,34.88,34.31,34.20,31.77,31.69,16.64(C=CCH3),and 14.33(OCH2CH3);IR(film)2960,2930,2860,1705(C=O),1610,1595,1460,1365,1260,1235,1185,1155,1045,and 695cm-1;MS(DCI)m/e 481/483(MH+,1∶1).
對(duì)于(E)-2-(3-溴苯基)-5-[4-(1-金剛烷基)-3-甲氧苯基]-2-戊烯酸乙酯(4i)量度=9.79mmol,產(chǎn)率=55%;
1H NMR(300MHz,CDCl3)δ7.37-7.41(m,1H,2-ArH),7.07-7.17(m,4H,3×2-ArH and C=CH),6.85(dt,J=2,8Hz,1H,5-ArH),6.61(dd,J=2,8Hz,1H,5-ArH),6.54(d,J=1Hz,1H,5-ArH),4.18(q,J=7Hz,2H,CO2CH2),3.75(s,3H,OCH3),2.68(t,J=8Hz,2H,ArCH2),2.35(q,J=8Hz,2H,ArCH2CH2),2.05(brs,9H,adamantyl),1.74(brs,6H,adamantyl),and 1.22(q,J=7Hz,3H,CO2CH2CH3);13CNMR(75MHz,CDCl3)δ166.57(C=O),158.75,144.70,139.21,137.29,133.32,132.48,130.43,129.41,128.38,126.49,121.85,120.25,111.95,60.99(CO2CH2),54.91(OCH3),40.64,37.13,36.69,34.60,31.43,and 14.22(CO2CH2CH3);IR(film)2905,2850,1715(C=O),1410,1250,1205,1185,and 1040cm-1;MS(DCI)m/e 523/525(MH+,1∶1).
對(duì)于(E)-2-(3-溴苯基)-5-[3-(1-金剛烷基)-4-羥苯基]-2-戊烯酸乙酯(4j)量度=10.1mmol,產(chǎn)率=76%(3∶1E∶Z異構(gòu)體);
1H NMR(300MHz,CDCl3)δ(E-isomer)7.43(dd,J=1,8Hz,1H,2-ArH),7.16-7.21(m,3H,C=CH and 2×2-ArH),6.93-6.96(m,2H,2-ArH and 5-ArH),6.76(dd,J=2,8Hz,1H,5-ArH),6.55(d,J=8Hz,1H,5-ArH),5.52(brs,1H,OH),4.25(q,J=7Hz,2H,CO2CH2),2.68(m,2H,ArCH2),2.36(m,2H,ArCH2CH2),2.13(brs,9H,adamantyl),1.81(s,6H,adamantyl),and1.30(t,J=7Hz,3H,CO2CH2CH3);(Z-isomer)7.50(m,1H,2-ArH),7.43(m,1H,2-ArH),7.23(m,2H,2-ArH),7.06(d,J=2Hz,1H,5-ArH),6.90(dd,J=2,8Hz,1H,5-ArH),6.59(d,J=8Hz,1H,5-ArH),6.26(m,1H,C=CH),5.52(brs,1H,OH),4.32(q,J=7Hz,2H,CO2CH2),2.78(m,4H,ArCH2CH2),2.13(m,9H,adamantyl),1.81(s,6H,adamantyl),and 1.34(t,J=7Hz,3H,CO2CH2CH3);13CNMR(75MHz,CDCl3)δ(E and Z isomers)167.95(C=O from Z-isomer),167.13(C=O from E-isomer),153.21,153.16,145.55,141.35,140.11,137.29,136.29,133.65,133.15,132.55,132.14,130.56,130.51,130.41,129.76,129.51,128.43,127.19,126.38,126.12,122.37,122.00,116.83,61.32(CO2CH2from E-isomer),61.23(CO2CH2from Z-isomer),40.54(adamantyl CH2),37.17(adamantyl CH2),36.67(adamantyl quaternary),34.93,34.49(CH2),32.20,32.03(CH2),29.13(adamantyl CH),15.23(CO2CH2CH3from Z-isomer),and 14.29(CO2CH2CH3from E-isomer);IR(film)3440(OH),2905,2850,1700(C=O),1270,1250,1210,1195,and 760cm-1;MS(DCI)m/e 509/511(1∶1,MH+);Exact mass spectrum(FAB) Calcd for C29H33BrO3(MH+)531.1511.Found531.1492.
對(duì)于(E)-2-(3-溴苯基)-3-(3,4-雙戊氧苯基)丙烯酸乙酯(4k)量度=5.39mmol,產(chǎn)率=36%;
1H NMR(300MHz,CDCl3)δ7.75(s,1H,C=CH),7.40-7.47(m,2H,2-ArH),7.25(t,J=8Hz,1H,2-ArH),7.16(dt,J=2,8Hz,1H,2-ArH),6.77(dd,J=2,8Hz,1H,3-ArH),6.70(d,J=8Hz,1H,3-ArH),6.40(d,J=2Hz,1H,3-ArH),4.23(q,J=7Hz,2H,CO2CH2),3.94(t,J=6.5Hz,2H,ArOCH2),3.48(t,J=6.5Hz,2H,ArOCH2),1.72-1.82(m,2H,ArOCH2CH2),1.58-1.65(m,2H,ArOCH2CH2),1.20-1.44(m,8H,4×CH2),1.25(t,J=7Hz,3H,CO2CH2CH3),and 0.86-0.94(m,6H,2×CH3);13CNMR(75MHz,CDCl3)δ167.46(C=O),150.37,148.24,140.99,138.92,132.92,130.60,130.24,128.77,128.35,126.69,125.65,122.56,114.21,112.33,68.88(ArOCH2),68.46(ArOCH2),61.22(CO2CH2),28.74,28.64,28.11,28.01,22.40,14.30(CO2CH2CH3),14.05,and 14.00;IR(film)2955,2935,2870,1710(C=O),1615,1595,1560,1515,1470,1430,1390,1380,1330,1270,1245,1190,1140,1070,1040,1000,805,and 690cm-1;MS(DCI)m/e 503/505(MH+,1∶1).
對(duì)于(E)-2-(3-三氟甲基苯基)-3-(4-癸氧苯基)丙烯酸乙酯(4l)量度=11.9mmol,產(chǎn)率=63%,12∶1E∶Z異構(gòu)體混合物。
1H NMR(300MHz,CDCl3)δ7.83(s,1H,C=CH),7.58(d,J=9Hz,1H,2-ArH),7.44-7.50(m,2H,2-ArH),7.39(d,J=7Hz,1H,2-ArH),6.92(d,J=9Hz,2H,3-ArH),6.66(d,J=9Hz,2H,3-ArH),4.23(q,J=7Hz,2H,CO2CH2),3.95(t,J=6Hz,2H,ArOCH2from minor isomer),3.87(t,J=6Hz,2H,ArOCH2),1.66-1.75(m,2H,ArOCH2CH2),1.20-1.38(m,17H,7×CH2and CO2CH2CH3),and 0.85(t,J=6Hz,3H,CH3);13CNMR(75MHz,CDCl3)δ167.41(C=O),160.16(3-ArC4),141.04,137.23,133.52,132.32(3-ArC),130.75,129.02,128.39,127.02(q,J3c,f=4Hz,2-ArC),126.33,124.35(q,J3c,f=4Hz,2-ArC),114.33(3-ArC),68.03(CO2CH2),61.20(ArOCH2),31.87,29.52,29.32,29.08,25.94,22.66,14.23,and 14.10;IR(KBr)2925,2855,1710(C=O),1600,1510,1325,1310,1250,1165,and 1130cm-1;MS(DCI)m/e 477(MH+).
對(duì)于(E)-2-(3-三氟甲基苯基)-3-(3-癸氧苯基)丙烯酸乙酯(4m)量度=5.4mmol,產(chǎn)率=50%;
1H NMR(300MHz,CDCl3)δ7.85(s,1H,C=CH),7.57(d,J=8Hz,1H,2-ArH),7.52(s,1H,2-ArH),7.47(t,J=8Hz,1H,2-ArH),7.38(d,J=8Hz,1H,2-ArH),7.08(t,J=8Hz,1H,3-ArH),6.75(dt,J=2,8Hz,1H,3-ArH),6.65(d,J=8Hz,1H,3-ArH),6.42(t,J=2Hz,1H,3-ArH),4.26(q,J=7Hz,2H,CO2CH2),3.53(t,J=7Hz,2H,ArOCH2),1.55-1.63(m,2H,ArOCH2CH2),1.22-1.30(m,17H,7×CH2and CO2CH2CH3),and 0.87(t,J=7Hz,3H,CH3);13CNMR(75MHz,CDCl3)δ167.07(C=O),158.76(3-ArC3),141.30,136.99,135.16,133.47,131.20,129.32,129.04,126.99(q,J3c,f=4Hz,2-ArC),124.44(q,J3c,f=4Hz,2-ArC),123.43,117.01,114.84,67.65(CO2CH2),61.41(ArOCH2),31.89,29.41,29.31,29.02,25.84,22.68,14.21,and 14.11;IR(film)3585,2925,2855,1710(C=O),1325,1230,and 1165cm-1;MS(DCI)m/e 477(MH+).
對(duì)于(E)-2-(3-三氟甲基苯基)-3-(2-癸氧苯基)丙烯酸乙酯(4n)量度=8.0mmol,產(chǎn)率=72%,約2∶1E/Z異構(gòu)體。
1H NMR(300MHz,CDCl3)δ8.24(s,1H,C=CH),7.13-7.74(m,4H,2-ArH),6.80-6.95(m,2H,3-ArH),6.53-6.62(m,2H,3-ArH),4.20-4.35(m,2H,CO2CH2for both isomers),4.01(t,J=7Hz,2H,CO2CH2for both isomers),1.75-1.88(m,2H,OCH2CH2for both isomers),1.22-1.55(m,14H,7×CH2for both isomers),1.14(t,J=7Hz,3H,CO2CH2CH3for both isomers),and 0.84-0.91(m,3H,CH3for both isomers).
對(duì)于(E)-2-(3-三氟甲基苯基)-3-[4-(2E),(6E)-3,7-二甲基-辛-2,6-二烯氧]苯基)-丙烯酸乙酯(4o)量度=2.73mmol,產(chǎn)率=62%,4∶1的E∶Z異構(gòu)體。
1H NMR(300MHz,CDCl3)δ7.83(s,1H,C=CH),7.31-7.60(m,4H,2-ArH),6.87-6.99(m,2H,3-ArH),6.68(dt,J=2,9Hz,2H,3-ArH),5.40(t,J=6.5Hz,1H,C=CHCH2OAr),5.02-5.08(m,1H,CH=C(CH3)2),4.55(d,J=6.5Hz,2H,ArOCH2from minor isomer),4.47(d,J=6.5Hz,2H,ArOCH2),4.19-4.31(m,2H,CO2CH2),1.96-2.08(m,4H,C=CHCH2CH2),1.51-1.76(m,9H,3×CH3),1.00-1.27(m,3H,CO2CH2CH3);13CNMR(75MHz,CDCl3)δ167.41(C=O),159.91(3-ArC4),141.59,141.01,137.22,133.53,133.16,132.30,131.85,130.76,130.03,129.68,129.03,128.57,127.04(q,J3c,f=4Hz,2-ArC),126.45,124.40(q,J3c,f=4Hz,2-ArC),123.70,119.13,118.96(3-ArC),114.68,114.56(3-ArC),64.88(ArOCH2),61.50,61.21(CO2CH2),39.48,29.71,26.23,25.67,17.67,16.64,14.23(CO2CH2CH3),and 13.93;IR(film)2980,2930,1710(C=O),1600,1510,1445,1380,1310,1250,1210,1165,and 1130cm-1;MS(DCI)m/e 473(MH+).
對(duì)于(E)-2-(3-三氟甲基苯基)-3-(3,4-雙癸氧基苯基)-丙烯酸乙酯(4p)量度=3.58mmol,產(chǎn)率=69%;
1H NMR(300MHz,CDCl3)δ7.80(s,1H,C=CH),7.40-7.59(m,4H,2-ArH),6.75(dd,J=2,8Hz,1H,3-ArH),6.69(d,J=8Hz,1H,3-ArH),6.31(d,J=2Hz,1H,3-ArH),4.23(q,J=7Hz,2H,CO2CH2),3.93(t,J=7Hz,2H,ArOCH2),3.39(t,J=7Hz,2H,ArOCH2),1.71-1.80(m,2H,CH2CH2O),1.53-1.61(m,2H,CH2CH2O),1.21-1.43(m,31H,14×CH2and OCH2CH3),and 0.83-0.89(m,6H,2×CH3);13CNMR(75MHz,CDCl3)δ167.35,150.43,148.31,141.33,137.85,133.66,129.15,128.33,136.80(q,J2c,f=38Hz,2-ArC),125.58,124.25,114.10,112.40,68.91(CH2O),68.38(CH2O),61.19(CO2CH2),31.91,29.57,29.35,29.04,28.93,25.92,25.76,22.68,14.25(OCH2CH3),and 14.11;IR(film)2925,2855,1710,1595,1515,1470,1430,1390,1325,1310,1270,1250,1165,1130,1095,1075,1045,and 700cm-1;MS(DCI)m/e 633(MH+).
對(duì)于(E)-2-(3-三氟甲基苯基)-3-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-丙烯酸乙酯(4q)量度=4.1mmol,產(chǎn)率=約50%,3∶1的產(chǎn)物(A)與起始物(B)的混合物。
1H NMR(300MHz,CDCl3)δ10.09(s,1H,CH=O,B),8.24(s,1H,ArH,B),8.05(s,1H,C=CH,A),7.95(s,1H,ArH,B),7.83-7.84(m,1H,ArH,A),7.58-7.66(m,5H,ArH),7.40-7.49(m,3H,ArH),6.75(dd,J=2,9Hz,1H,ArH),4.30(q,J=7Hz,2H,CO2CH2),1.79(s,4H,CH2CH2,B),1.75(s,4H,CH2CH2,A),1.41(s,12H,4×CH3,B),1.36(brs,12H,4×CH3,A),and 1.32(t,J=7Hz,3H,CO2CH2CH3);13CNMR(75MHz,CDCl3)δ192.44(C=O,B),168.80(C=O,A),146.22,145.12,141.80,136.90,134.64,133.74,131.79,131.54,131.34,130.82,130.41,128.92,128.31,127.24,126.96,126.84,125.62,125.62,125.43,125.27,124.74,124.51,121.65,61.38(CO2CH2),34.91,34.83,34.70,34.56,32.41(4×CH3),and 14.26(CO2CH2CH3);IR(KBr)2960,2930,2860,1710(C=O,A),1680(C=O,B),1470,1320,1310,1240,and 1165cm-1;MS(DCI)m/e 481(MH+,A)and 267(MH+,B).
對(duì)于(E)-2-(3-三氟甲基苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘)-2-戊烯酸乙酯(4r)量度=4.09mmol,產(chǎn)率=56%;
1H NMR(300MHz,CDCl3)δ7.51(brd,J=8Hz,1H,2-ArH),7.37(t,J=8Hz,1H,2-ArH),7.30(brs,1H,2-ArH),7.17(d,J=8Hz,1H,2-ArH),7.16(t,J=8Hz,1H,C=CH),7.03(d,J=8Hz,5-ArH),6.98(d,J=2Hz,1H,5-ArH),6.81(dd,J=2,8Hz,1H,5-ArH),4.18(q,J=7Hz,2H,CO2CH2),2.68(t,J=8Hz,2H,ArCH2),2.32(q,J=8Hz,2H,ArCH2CH2),1.64(brs,4H,CH2CH2),1.25(s,6H,2×CH3),1.24(t,J=7Hz,3H,CO2CH2CH3),and 1.21(s,6H,2×CH3);13CNMR(75MHz,CDCl3)δ166.47(C=O),145.13,144.80,142.77,137.37,136.00,133.22,133.07,130.26(q,J2c,f=32Hz,2-ArC),128.32,126.65,126.50(q,J3c,f=4Hz,2-ArC),125.65,124.16(q,J3c,f=4Hz,2-ArC),61.01(CO2CH2),35.10,34.64,34.13,33.95,31.86,31.77,31.57 and 14.19(CO2CH2CH3);IR(film)2960,2930,2860,1715(C=O),1495,1460,1445,1385,1365,1325,1310,1250,1180,1165,1130,1095,1075,1045,810,and 700cm-1;MS(DCI)m/e 459(MH+).
對(duì)于(E)-2-(4-氟苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-戊烯酸乙酯(4s)量度=2.66mmol,產(chǎn)率=58%;
1H NMR(300MHz,CDCl3)δ7.17(d,J=8Hz,1H,5-ArH),7.09(t,J=8Hz,1H,C=CH),6.80-6.98(m,6H,4×2-ArH and 2×5-ArH),4.17(q,J=7Hz,2H,CO2CH2),2.66(t,J=8Hz,2H,ArCH2),2.32(q,J=8Hz,2H,ArCH2CH2),1.64(brs,4H,CH2CH2),1.25(s,6H,2×CH3),1.24(t,J=7Hz,3H,CO2CH2CH3),and 1.21(s,6H,2×CH3);13CNMR(75MHz,CDCl3)δ166.97(C=O),162.02(d,J1c,f=246Hz,2-ArC),144.73,144.31,142.68,137.58,133.51,131.26(d,J3c,f=8Hz,2-ArC),125.58,125.74,114.72(J2c,f=21Hz,2-ArC),60.86(CO2CH2),35.11,35.07,34.67,34.14,33.95,31.89,31.80,31.55,and 14.24(CO2CH2CH3);IR(film)2960,2925,2860,1715(C=O),1640,1605,1510,1495,1460,1410,1385,1365,1250,1220,1205,1185,1160,1095,1070,1045,840,825,and 765cm-1;MS(DCI)m/e 409(MH+).
對(duì)于(E)-2-(3-氟苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-戊烯酸乙酯(4t)量度=2.29mmol,產(chǎn)率=57%;
1H NMR(300MHz,CDCl3)δ7.17-7.24(m,2H,1×2-ArH and 1×5-ArH),7.11(t,J=8Hz,1H,C=CH),6.98(d,J=2Hz,1H,5-ArH),6.94(apparent tt,J=2,8Hz,1H,2-ArH),6.82(dd,J=2,8Hz,1H,5-ArH),6.67(dt,J=2,8Hz,1H,2-ArH),6.58(apparent dt,J=2,8Hz,1H,2-ArH),4.17(q,J=7Hz,2H,CO2CH2),2.68(t,J=8Hz,2H,ArCH2),2.33(q,J=8Hz,2H,ArCH2CH2),1.64(brs,4H,CH2CH2),1.25(s,6H,2×CH3),1.24(t,J=7Hz,3H,CO2CH2CH3),and 1.21(s,6H,2×CH3);13CNMR(75MHz,CDCl3)δ166.65(C=O),162.30(d,J1c,f=246Hz,2-ArC),144.77,144.63,142.73,137.49,137.36(d,J3c,f=8Hz,2-ArC),133.44,129.25(d,J3c,f=9Hz,2-ArC),126.56,125.72,125.35(d,J4c,f=3Hz,2-ArC),116.64(J2c,f=22Hz,2-ArC),114.24(J2c,f=22Hz,2-ArC),60.92(CO2CH2),35.12,35.08,34.64,34.14,33.96,31.87,31.80,31.55,and 14.23(CO2CH2CH3);IR(film)2960,2930,2860,1715(C=O),1640,1610,1585,1490,1460,1440,1410,1385,1365,1260,1230,1190,1175,1135,1070,1045,885,825,and 790cm-1;MS(DCI)m/e 409(MH+).
對(duì)于(E)-2-苯基-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-戊烯酸乙酯(4u)量度=2.66mmol,產(chǎn)率=53%;
1H NMR(300MHz,CDCl3)δ7.23-7.30(m,3H,2-ArH),7.17(d,J=8Hz,1H,5-ArH),7.08(t,J=8Hz,1H,C=CH),6.99(d,J=2Hz,1H,5-ArH),6.92-6.95(m,2H,2-ArH),6.82(dd,J=2,8Hz,1H,5-ArH),4.17(q,J=7Hz,2H,CO2CH2),2.66(t,J=8Hz,2H,ArCH2),2.34(q,J=8Hz,2H,ArCH2CH2),1.64(brs,4H,CH2CH2),1.25(s,6H,2×CH3),1.24(t,J=7Hz,3H,CO2CH2CH3),and 1.21(s,6H,2×CH3);13CNMR(75MHz,CDCl3)δ167.18(C=O),144.59,143.92,142.58,137.73,135.25,129.57,127.82,127.25,126.53,125.71,60.76(CO2CH2),35.14,35.09,34.75,34.15,33.94,31.88,31.81,31.47,and 14.25(CO2CH2CH3);IR(film)2960,2925,2860,1715(C=O),1495,1460,1445,1385,1365,1250,1205,1185,1070,1045,1030,825,775,and 700cm-1;MS(DCI)m/e 391(MH+).
對(duì)于(E)-2-(3-三氟甲苯基)-5-[3-(1-金剛烷基)-4-羥苯基]-2-戊烯酸乙酯(4v)量度=6.17mmol,產(chǎn)率=32%(3∶1E∶Z異構(gòu)體);
1H NMR(300MHz,CDCl3)δ(E-isomer)7.53(d,J=8Hz,1H,2-ArH),7.41(m,1H,2-ArH),7.24(s,1H,2-ArH),7.17(m,2H,C=CH and 2-ArH),6.89(d,J=2Hz,1H,5-ArH),6.72(dd,J=2,8Hz,1H,5-ArH),6.51(d,J=8Hz,1H,5-ArH),4.87(s,1H,OH),4.20(q,J=7Hz,2H,CO2CH2),2.66(t,J=7Hz,2H,ArCH2),2.31(q,J=7Hz,2H,ArCH2CH2),2.07(m,9H,adamantyl),1.76(s,6H,adamantyl),and 1.25(t,J=7Hz,3H,CO2CH2CH3);(Z)-isomer,partially obscured7.03(d,J=2Hz,1H,5-ArH),6.57(d,J=8Hz,1H,5-ArH),6.26(m,1H,5-ArH),4.88(s,1H,OH),4.27(q,J=7Hz,2H,CO2CH2),2.76(m,4H,ArCH2CH2),and 1.29(t,J=7Hz,3H,CO2CH2CH3);13CNMR(75MHz,CDCl3)δ(E-and Z-isomers)δ166.64(C=O),152.88,152.81,145.32,142.09,138.93,136.23,135.99,133.20,133.12,132.80,132.34,130.80,130.26(d,J2c,f=32Hz,2-ArC),128.63,128.34,127.24,127.18,126.49(d,J3c,f=4Hz,2-ArC),126.31,125.90,124.19(d,J3c,f=4Hz,2-ArC),116.74,61.13(CO2CH2from E-isomer),61.05(CO2CH2from Z-isomer),40.54(adamantyl CH2from Z-isomer),40.49(adamantyl CH2from E-isomer),37.05(adamantyl CH2),36.59(adamantyl quaternary),34.84(CH2from Z-isomer),34.42(CH2from E-isomer),32.13(CH2from Z-isomer),31.91(CH2from E-isomer),29.01(adamantyl CH),and 14.19(CO2CH2CH3);IR(film)3450(OH),2905,2850,1695(C=O),1325,1255,1210,1180,and 760cm-1;MS(DCI)m/e 499(MH+),488(M+),487(M-H)+,135(C10H+15).Anal.Calcd for C30H33O3F3C,72.27;H,6.67.FoundC,72.70;H,7.01.
對(duì)于(E)-2-(3-三氟甲苯基)-5-[4-(1-金剛烷基)-3-羥苯基]-2-戊烯酸乙酯(4w)量度=6.17mmol,產(chǎn)率=32%;
1H NMR(300MHz,CDCl3)δ7.53-7.55(d,J=8Hz,1H,2-ArH),7.41(t,J=8Hz,1H,2-ArH),7.33(s,1H,2-ArH),7.10-7.17(m,2H,C=CH and 2-ArH),7.07(d,J=8Hz,1H,5-ArH),6.60(dd,J=2,8Hz,1H,5-ArH),6.34(d,J=2Hz,1H,5-ArH),4.83(s,1H,OH),4.19(q,J=7Hz,2H,CO2CH2),2.63(t,J=8Hz,2H,ArCH2),2.32(q,2H,ArCH2CH2),2.08(brs,9H,adamantyl),1.75(s,6H,adamantyl),and 1.24(t,J=7Hz,3H,CO2CH2CH3);13CNMR(75MHz,CDCl3)δ166.60(C=O),154.40,144.98,139.21,135.94,134.40,133.34,133.13,130.30(d,J2c,f=32Hz,2-ArC),128.40,127.05,126.47(d,J3c,f=4Hz,2-ArC),124.25(d,J3c,f=4Hz,2-ArC),124.08(d,J1c,f=271Hz,CF3),120.55,116.73,61.15(CO2CH2),40.59(adamantyl CH2),37.04(adamantyl CH2),36.40(adamantyl quaternary),34.00(CH2),31.24(CH2),29.01(adamantyl CH),and 14.16(CO2CH2CH3);IR(KBr)3460(OH),2905,2850,1695(C=O),1420,1325,1265,1165,and 1125cm-1;MS(DCI)m/e 499(MH+),498(M+),497(M-H)+,135(C10H15+).Anal.Calcd for C30H33O3F3C,72.27;H,6.67.FoundC,72.64;H,6.60.
對(duì)于(E)-2-苯基-5-[4-(1-金剛烷基)-3-甲氧苯基]-2-戊烯酸乙酯(4x)量度=7.00mmol,產(chǎn)率=59%;
1H NMR(300MHz,CDCl3)δ7.22-7.33(m,3H,2-ArH),7.08(t,J=8Hz,1H,C=CH),7.06(d,J=8Hz,1H,5-ArH),6.96-7.01(m,2H,2-ArH),6.62(dd,J=2,8Hz,1H,5-ArH),6.54(d,J=2Hz,1H,5-ArH),4.16(q,J=7Hz,2H,CO2CH2),3.74(s,3H,OCH3),2.67(t,J=8Hz,2H,ArCH2),2.37(q,J=8Hz,2H,ArCH2CH2),2.03-2.08(m,9H,adamantyl),1.74(brs,6H,adamantyl),and 1.24(t,J=7Hz,3H,CO2CH2CH3);13CNMR(75MHz,CDCl3)δ167.17(C=O),158.72,143.76,139.50,136.36,135.24,134.57,129.62,127.84,127.29,126.36,120.25,111.97,60.80(CO2CH2),54.89(OCH3),40.66,37.14,36.68,34.67,31.32,29.11,and 14.24(CO2CH2CH3);IR(film)2905,2850,1710(C=O),1610,1465,1450,1415,1250,1205,1185,1165,1140,1100,1045,1030,760,and 700cm-1;MS(DCI)m/e 445(MH+).
對(duì)于(E)-2-(3-三氟甲苯基)-5-[2-(1-金剛烷基)-4-甲氧苯基]-2-戊烯酸乙酯(4y)量度=1.41mmol,產(chǎn)率=41%;
1H NMR(300MHz,CDCl3)δ7.54(d,J=8Hz,1H,2-ArH),7.43(t,J=8Hz,1H,2-ArH),7.35(s,1H,2-ArH),7.18-7.28(m,2H,C=CH and 2-ArH),6.90(d,J=8Hz,1H,5-ArH),6.83(d,J=3Hz,1H,5-ArH),6.63(dd,J=3,8Hz,1H,5-ArH),4.21(q,J=7Hz,2H,CO2CH2),3.74(s,3H,OCH3),2.97(m,2H,ArCH2),2.35(m,2H,ArCH2CH2),2.03(brs,3H,adamantyl),1.91(m,6H,adamantyl),1.72(m,6H,adamantyl),and 1.26(t,J=7Hz,3H,CO2CH2CH3);13CNMR(75MHz,CDCl3)δ166.54(C=O),157.69,149.05,144.95,136.04,133.06,132.66,131.34,130.40(d,J2c,f=32Hz,2-ArC),128.41,126.46(d,J3c,f=4Hz,2-ArC),124.30(d,J3c,f=4Hz,2-ArC),113.17,110.00,61.12(CO2CH2),55.09(OCH3),42.10(adamantyl CH2),37.85(adamantyl quaternary),36.74(adamantyl CH2),33.31(CH2),32.66(CH2),29.07(adamantyl CH),and 14.20(CO2CH2CH3);IR(film)2910,2850,1715(C=O),1605,1575,1465,1445,1325,1255,1165,1130,1075,760,710,and 700cm-1;MS(DCI)m/e 513(MH+),135(C10H+15).Exact mass spectrum(FAB)Calcd for C31H36O3F3(MH+);513.2617.Found513.2601.
對(duì)于(E)-2-(3-三氟苯基)-3-[4-(1-金剛烷基)-3-甲氧苯基]-丙烯酸乙酯(4z)量度=4.26mmol,產(chǎn)率=65%;
1H NMR(300MHz,CDCl3)δ7.84(s,1H,C=CH),7.42-7.61(m,4H,2-ArH),7.07(d,J=8Hz,1H,3-ArH),6.74(dd,J=2,8Hz,1H,3-ArH),6.32(d,J=2Hz,1H,3-ArH),4.25(q,J=7Hz,2H,CO2CH2),3.31(s,3H,OCH3),1.98(brs,9H,adamantyl),1.71(s,6H,adamantyl),and 1.27(t,J=7Hz,3H,CO2CH2CH3);13CNMR(75MHz,CDCl3)δ167.23(C=O),158.28,141.14,140.80,137.50,133.53,132.40,131.09(d,J2c,f=32Hz,2-ArC),130.07,129.17,126.99(d,J3c,f=4Hz,2-ArC),126.56,124.38(d,J3c,f=4Hz,2-ArC),124.01(d,J1c,f=271Hz,CF3),112.59,61.32(CO2CH2),54.17(OCH3),40.26(adamantyl CH2),37.14(adamantyl quaternary),36.99(adamantyl CH2),28.92(adamantyl CH),and 14.23(CO2CH2CH3);IR(film)2905,2850,1710(C=O),1325,1230,1165,and 1130cm-1;MS(DCI)m/e 485(MH+),135(C10H15+).Anal.Calcd for C29H31O3F3C,71.88;H,6.45,F(xiàn)oundC,70.46;H,6.21.
對(duì)于(E)-2-(3-三氟甲苯基)-5-[4-(1-金剛烷基)-3-叔丁基二甲基甲硅烷氧基苯基]-2-戊烯酸乙酯(4aa)量度=4.94mmol,產(chǎn)率=59%;
1H NMR(300MHz,CDCl3)δ7.53(m,1H,ArH),7.39(m,1H,ArH),7.33(s,1H,ArH),7.15(m,1H,C=CH),7.08(m,2H,ArH),6.60(dd,J=2,8Hz,1H,5-ArH),6.47(d,J=2Hz,1H,5-ArH),4.19(q,J=7Hz,2H,CO2CH2),2.63(m,2H,ArCH2),2.31(m,2H,ArCH2CH2),2.06(m,9H,adamantyl),1.74(s,6H,adamantyl),1.24(t,J=7Hz,3H,CO2CH2CH3),0.99(s,9H,SiC(CH3)3),and 0.25(s,6H,SiC(CH3)2);13CNMR(75MHz,CDCl3)δ166.41(C=O),154.58,144.81,138.73,137.46,135.97,133.39,133.05,128.39,127.09,126.47(d,J3c,f=4Hz,2-ArC),124.23(d,J3c,f=4Hz,2-ArC),120.33,119.06,61.05(CO2CH2),40.43(adamantyl CH2),37.05(adamantyl CH2),36.55(adamantyl quaternary),34.25(CH2),31.44(CH2),29.03(adamantyl CH),26.38(SiC(CH3)3),18.89(SiC(CH3)3),14.19(CO2CH2CH3),and-3.43(Si(CH3)2);IR(film)2955,2930,2905,2855,1715(C=O),1415,1325,1265,860,840,780,and 760cm-1;MS(DCI)m/e 613(MH+),135(C10H+15).Anal.Calcd for C36H47O3F3SiC,70.56;H,7.73.FoundC,70.47;H,7.66.
實(shí)施例4合成化合物5的一般方法在氬氣環(huán)境下將酯4(1當(dāng)量)的無水THF(0.1-0.2M)溶液冷卻至-78℃。加入二異丁基氫化鉛(1M于己烷,2.5當(dāng)量),并將反應(yīng)混合物溫?zé)嶂?℃-室溫。通過緩慢加入甲醇并接著用飽和氯化銨處理終止反應(yīng)。所得混合物攪拌15min,然后在乙醚和1N HCl溶液間分配。攪拌各層,直至水相中所有固體溶解。分離有機(jī)層,用飽和氯化鈉溶液洗滌,于無水硫酸鎂上干燥,過濾,并濃縮。通過柱層析純化(30∶1-40∶1硅膠/粗品;用5%-15%乙酸乙酯的己烷洗脫),得到目的化合物。
對(duì)于(Z)-2-(3-溴苯基)-3-苯基-2-丙烯醇(5a)量度=2.14mmol,產(chǎn)率=78%;
1H NMR(300MHz,CDCl3)δ7.38-7.43(m,2H,2-ArH),7.10-7.20(m,5H,ArH),6.96-7.00(m,2H,ArH),6.70(brs,1H,C=CH),and 4.41(d,J=1.5Hz,2H,CH2OH);13CNMR(75MHz,CDCl3)δ140.81,139.83,135.86,131.50,130.63,130.31,129.22,128.10,127.70,127.18,122.76,and 68.35(CH2OH);IR(film)3320(OH),3060,3020,1590,1560,1495,1470,1450,1410,1095,1070,1030,1000,920,880,790,785,and 700cm-1;MS(DCI)m/e 288/290(MH+,1∶1),271/273(M+-OH,1∶1).
對(duì)于(Z)-2-(3-溴苯基)-3-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-丙烯醇(5b)量度=5.44mmol,產(chǎn)率=99%;
1H NMR(300MHz,CDCl3)δ7.42-7.47(m,2H,2-ArH),7.18-7.28(m,2H,2-ArH),7.13(d,J=8Hz,1H,3-ArH),6.88(d,J=2Hz,1H,3-ArH),6.83(dd,J=2,8Hz,1H,3-ArH),6.63(brs,1H,C=CH),4.42(dd,J=1.5,7Hz,2H,CH2OH),1.60(brs,4H,CH2CH2),1.20(s,6H,2×CH3)and 0.98(s,6H,2×CH3);IR(film)3000-3300(br,OH),2950,2920,2860,1555,1500,1470,1460,1415,1360,1350,1035,915,820,and 700cm-1;MS(DCI)m/e 398/400(M+,1∶1),381/383(M+-OH,1∶1).
對(duì)于(Z)-2-(3-溴苯基)-3-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2-丙烯醇(5c)量度=2.66mmol,產(chǎn)率=87%;
1H NMR(300MHz,CDCl3)δ7.62(d,J=9Hz,2H,ArH),7.39-7.48(m,4H,ArH),7.13-7.15(m,2H,ArH),6.83-6.87(m,2H,ArH and C=CH),4.70(dd,J=1,6Hz,2H,CH2OH),1.73(s,4H,CH2CH2),and1.34-1.37(m,12H,4×CH3);13CNMR(75MHz,CDCl3)δ144.72,144.60,140.93,139.29,132.65,131.53,130.87,130.66,130.56,128.34,128.02,126.60,125.89,125.02,124.64,122.76,68.55(CH2OH),35.04(CH2CH2),34.58,34.53,and 32.47(4×CH3);IR(KBr)3400(br,OH),2960,2925,2860,1560,1470,and 1360cm-1;MS(DCI)m/e 451/449(MH+,1∶1),433/431(MH+-H2O,1∶1).
對(duì)于(Z)-2-(3-溴苯基)-3-(4-癸氧苯基)-2-丙烯醇(5d)量度=7.40mmol,產(chǎn)率=78%1H NMR(300MHz,CDCl3)δ7.37-7.42(m,2H,2-ArH),7.12-7.24(m,2H,2-ArH),6.89(d,J=8Hz,2H,3-ArH),6.61-6.67(m,3H,2×3-ArH and C=CH),4.39(dd,J=1,6Hz,2H,CH2OH),3.86(t,J=7Hz,2H,ArOCH2),1.71(quintet,J=7Hz,2H,ArOCH2CH2),1.57(t,J=6Hz,1H,OH),1.18-1.43(m,14H,7×CH2),and 0.86(t,J=7Hz,3H,CH3);13CNMR(75MHz,CDCl3)δ158.33,141.22,137.61,131.57,130.48,130.36,128.11,127.80,127.62,122.81,114.09,68.74(CH2OH),67.91(ArOCH2),31.89,29.55,29.37,29.31,29.21,26.01,22.68,and 14.12;IR(film)3400(br,OH),2950,2940,2920,2850,1605,1590,1555,1510,1475,1400,1395,1375,1300,1250,1175,1090,1060,1050,1030,995,975,880,830,790,775,and 720cm-1;MS(DCI)m/e 444/446(MH+,1∶1).
對(duì)于(Z)-2-(3-溴苯基)-3-(3,4-雙癸氧苯基)-2-丙烯醇(5e)量度=0.84mmol,產(chǎn)率=87%;
1H NMR(300MHz,CDCl3)δ7.39-7.43(m,2H,2-ArH),7.15-7.24(m,2H,2-ArH),6.67(d,J=8Hz,1H,3-ArH),6.59(dd,J=2,8Hz,1H,3-ArH),6.58(s,1H,C=CH),6.42(d,J=2Hz,1H,3-ArH),4.39(brs,2H,CH2OH),3.91(t,J=7Hz,2H,ArC4OCH2),3.54(t,J=7Hz,2H,ArC3OCH2),1.75(quint,J=7Hz,2H,ArC4OCH2CH2),1.59(quint,J=7Hz,2H,ArC3OCH2CH2),1.24-1.40(m,28H,14×CH2),and 0.83-0.89(m,6H,2×CH3);13CNMR(75MHz,CDCl3)δ148.44(3-ArC4),148.27(3-ArC3),141.50,137.70,131.80,130.42,128.52,127.78,122.83,122.68,113.90,112.96,69.05,68.75,68.65,31.93,29.65,29.60,29.57,29.37,29.20,29.04,25.98,25.89,22.70,and 14.12;IR(KBr)3100-3400(br,OH),2955,2920,2850,1515,1470,1425,1270,1235,and 1140cm-1;MS(DCI)m/e 603/601(MH+,1∶1),585/583(MH+-H2O,1∶1).
對(duì)于(Z)-2-(3-溴苯基)-5-苯基-2-戊烯醇(5f)量度=5.80mmol,產(chǎn)率=95%;
1H NMR(300MHz,CDCl3)δ7.39(dt,J=2,8Hz,1H,2-ArH),7.08-7.29(m,7H,3×2-ArH and 4×5-ArH),6.98(dt,J=2,8Hz,1H,5-ArH),5.77(t,J=7.5Hz,1H,C=CH),4.25(s,2H,CH2OH),2.67(t,J=7.5Hz,2H,ArCH2),and 2.30(q,J=7.5Hz,2H,ArCH2CH2);13CNMR(75MHz,CDCl3)δ141.17,140.44,139.72,131.33,130.10,129.70,128.78,128.37,128.22,127.17,125.85,122.26,67.70(CH2OH),35.67,and 30.26;IR(film)3350(br,OH),3085,3060,3025,2920,2860,1590,1560,1495,1475,1455,1410,1365,1100,1080,1070,1030,995,790,750,700,and 670cm-1;MS(DCI)m/e 299/301(M+-OH,1∶1).
對(duì)于(Z)-2-(3-溴苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-戊烯醇(5g)量度=3.2mmol,產(chǎn)率=87%;
1H NMR(300MHz,CDCl3)δ7.38(ddd,J=1,2,8Hz,1H,2-ArH),7.27(t,J=2Hz,1H,2-ArH),7.13-7.24(m,2H,2-ArH),7.01(d,J=2Hz,1H,5-ArH),6.95(dt,J=1,8Hz,1H,5-ArH),6.86(dd,J=2,8Hz,1H,5-ArH),5.80(m,1H,C=CH),4.26(m,2H,CH2OH),2.61(t,J=7Hz,2H,ArCH2),2.28(q,J=7Hz,2H,ArCH2CH2),1.44(m,1H,OH),1.25(s,6H,2×CH3),and 1.24(s,6H,2×CH3);13CNMR(75MHz,CDCl3)δ144.66,142.44,140.63,139.53,138.19,131.47,130.18,129.82,129.42,127.31,126.47,125.75,122.34,107.61,67.88(CH2OH),35.59,35.18,35.12,34.16,33.96,31.93(CH3),31.88,and 30.49;IR(film)3335(br,OH),2960,2925,2860,1470,1460,1360,1070,790,760cm-1;MS(FAB)m/e 426/428(MH+,1∶1).Anal.Calcd for C25H31BrOC,70.25;H,7.31.FoundC,70.15;H,7.20.
對(duì)于(2Z),(4E)-2-(3-溴苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-已二烯醇(5h)量度=3.47mmol,產(chǎn)率=93%;
1H NMR(300MHz,CDCl3)δ7.49(d,J=2Hz,1H,2-ArH),7.41(dt,J=2,8Hz,1H,2-ArH),7.19-7.27(m,4H,2×2-ArH and 2×5-ArH),7.09(dd,J=2,8Hz,1H,5-ArH),6.74(dt,J=1.5,12Hz,1H,C=CH),6.45(brd,J=12Hz,1H,C=CH),4.46(d,J=1.5Hz,2H,CH2OH),2.22(d,J=1.5Hz,3H,C=CCH3),1.65(brs,4H,CH2CH2),and 1.24(s,12H,4×CH3);13CNMR(75MHz,CDCl3)δ139.99,139.07,131.87,130.46,129.86,127.82,126.46,125.19,123.83,123.08,122.47,122.15,67.87(CH2OH),35.12,34.97,34.30,34.10,31.81,31.75,and 16.11(C=CCH3);IR(film)3335(br,OH),2960,2930,2860,1590,1555,1495,1470,1460,1385,1360,1215,1085,1070,885,825,785,760,700,and 680cm-1;MS(DCI)m/e 438/440(M+,1∶1),421/423(M+-OH).
對(duì)于(Z)-2-(3-溴苯基)-5-[4-(1-金剛烷基)-3-甲氧苯基]-2-戊烯醇(5i)量度=5.4mmol,產(chǎn)率=78%;
1H NMR(300MHz,CDCl3)δ7.36-7.39(m,1H,2-ArH),7.23(t,J=2Hz,1H,2-ArH),7.16(t,J=8Hz,1H,2-ArH),7.07(d,J=8Hz,1H,3-ArH),6.94(dt,J=2,8Hz,1H,2-ArH),6.63(dd,J=2,8Hz,1H,3-ArH),6.56(d,J=2Hz,1H,3-ArH),5.77(t,J=8Hz,1H,C=CH),4.25(d,J=5Hz,2H,CH2OH),3.75(s,3H,OCH3),2.62(t,J=8Hz,2H,ArCH2),2.28(q,J=8Hz,2H,ArCH2CH2),2.05(brs,9H,adamantyl),and 1.74(brs,6H,adamantyl);13CNMR(75MHz,CDCl3)δ158.71,140.60,139.93,139.67,136.21,131.49,130.18,129.81,129.22,127.30,126.30,122.32,120.31,112.00,67.85(CH2OH),54.92(OCH3),40.64,37.14,36.66,35.48,30.33,and 29.10;IR(film)3355(br,OH),2900,2850,1560,1450,1410,and 1245cm-1;MS(DCI)m/e 483/481(MH+,1∶1),465/463(MH+-H2O,1∶1).
對(duì)于(Z)-2-(3-溴苯基)-5-[3-(1-金剛烷基)-4-羥苯基]-2-戊烯醇(5j)量度=2.6mmol,產(chǎn)率=95%(3∶1,Z∶E);
1H NMR(300MHz,CDCl3)δ(Z-isomer)7.37(m,1H,2-ArH),7.17(m,2H,2-ArH),6.99(m,1H,2-ArH),5.77(t,J=7Hz,1H,C=CH),5.09(brs,1H,ArOH),4.26(s,2H,CH2OH),2.57(t,J=7Hz,2H,ArCH2),2.25(q,J=7Hz,2H,ArCH2CH2),2.06(m,9H,admantyl),and 1.76(s,6H,adamantyl);(E-isomer,partially obscured)7.55(m,1H,2-Ar),5.91(t,J=8Hz,1H,C=CH),4.21(s,2H,CH2OH),2.71(t,J=7Hz,2H,ArCH2),and 2.53(q,J=7Hz,2H,ArCH2CH2);13CNMR(75MHz,CDCl3)δ153.11,152.77,143.39,140.62,139.43,138.33,136.19,133.05,132.64,131.45,130.16,129.99,129.82,129.60,129.38,127.59,127.36,127.15,126.67,126.36,124.86,122.60,122.37,116.83,116.61,67.91,59.45,40.55,40.45,37.08,36.60,35.31,35.08,31.04,30.78,29.05,and 25.61;IR(KBr)3520(OH),3345(br,OH),2900,2850,1450,1420,1240,1100,995,and 785cm-1;MS(DCI)m/e 466/468(M+,1∶1),241,135(C10H+15).Anal.Calcd for C27H31BrO2C,69.38;H,6.68.FoundC,69.06;H,6.91.
對(duì)于(Z)-2-(3-溴苯基)-3-(3,4-雙戊氧苯基)-2-丙烯醇(5k)量度=1.67mmol,產(chǎn)率=94%;
1H NMR(300MHz,CDCl3)δ7.39-7.44(m,2H,2-ArH),7.11-7.24(m,2H,2-ArH),6.67(d,J=8Hz,1H,3-ArH),6.60(dd,J=2,8Hz,1H,3-ArH),6.58(t,J=1.5Hz,1H,C=CH),6.42(d,J=2Hz,1H,3-ArH),4.39(dd,J=1.5,6Hz,2H,CH2OH),3.91(t,J=6.5Hz,2H,3-ArOCH2),3.54(t,J=6.5Hz,2H,3-ArOCH2),1.71-1.81(m,2H,3-ArOCH2CH2),1.55-1.65(m,2H,3-ArOCH2CH2),1.29-1.44(m,8H,4×CH2),and 0.86-0.92(m,6H,2×CH2);13CNMR(75MHz,CDCl3)δ148.41,148.23,141.49,137.69,131.78,130.43,128.50,127.79,127.76,122.83,122.68,113.81,112.87,69.00(3-ArOCH2),68.75(CH2OH),68.60(3-ArOCH2),28.87,28.70,28.16,28.05,22.46,22.40,14.08 and 14.04;IR(film)3355(OH),3265(OH),2955,2930,2870,2855,1515,1465,1430,1270,1235,1170,1140,1085,1070,1035,985,800,and 785cm-1;MS(DCI)m/e 461/463(MH+,1∶1),443/445(M+-OH).
對(duì)于(Z)-2-(3-三氟甲苯基)-3-(4-癸氧苯基)-2-丙烯醇(5l)量度=7.4mmol,產(chǎn)率=80%;
1H NMR(300MHz,CDCl3)δ7.51-7.54(m,2H,2-ArH),7.39-7.42(m,2H,2-ArH),6.85(dt,J=3,8Hz,2H,3-ArH),6.61-6.67(m,3H,2×3-ArH and C=CH),4.44(dd,J=1,6Hz,2H,CH2OH),3.85(t,J=6Hz,ArOCH2),1.71(quint,J=6Hz,2H,ArOCH2CH2),1.24-1.41(m,14H,7×CH2),0.85(t,J=6Hz,3H,CH3);13CNMR(75MHz,CDCl3)δ158.40(3-ArC4),139.86,137.59,132.57,130.42(3-ArC),129.20,128.13,127.99,125.60(q,J3c,f=4Hz,2-ArC),124.16(q,J3c,f=4Hz,2-ArC),114.14(3-ArC),68.65,67.93,31.88,29.54,29.36,29.30,29.19,25.99,22.66,and 14.10;IR(KBr)3550,3400(br,OH),2960,2940,2920,2850,1605,1510,1475,1420,1390,1325,1310,1255,1180,and 1160cm-1;MS(DCI)m/e 434(M+),417(M+-H2O).
對(duì)于(Z)-2-(3-三氟甲苯基)-3-(3-癸氧苯基)-2-丙烯醇(5m)量度=2.7mmol,產(chǎn)率=68%;
1H NMR(300MHz,CDCl3)δ7.52-7.54(m,2H,2-ArH),7.37-7.45(m,2H,2-ArH),7.02(t,J=8Hz,1H,3-ArH),6.72(brs,1H,C=CH),6.65(dt,J=2,8Hz,1H,3-ArH),6.54(d,J=8Hz,1H,3-ArH),6.42(t,J=2Hz,1H,3-ArH),4.46(dd,J=1,5Hz,2H,CH2OH),3.58(t,J=7Hz,2H,ArOCH2),1.55-1.68(m,2H,ArOCH2CH2),1.21-1.37(m,14H,7×CH2),and 0.87(t,J=7Hz,3H,CH3);13CNMR(75MHz,CDCl3)δ158.74(3-ArC),139.90,139.69,136.94,132.51,129.24,129.09,128.17,125.60(q,J3c,f=4Hz,2-ArC),124.24(q,J3c,f=4Hz,2-ArC),121.78,114.48,114.29,68.31,67.65,31.89,29.55,29.31,29.08,25.88,22.68,and 14.11;IR(film)3330(br,OH),2925,2855,1600,1570,1470,1435,1325,1265,1165,and 1130cm-1;MS(DCI)m/e 435(MH+),417(M+-H2O).
對(duì)于(Z)-2-(3-三氟甲苯基)-3-(2-癸氧苯基)-2-丙烯醇(5n)量度=5.7mmol,產(chǎn)率=99%,約5∶3的Z∶E混合物。于室溫下用乙酸酐(0.73g,7.2mmol)和4,4-二甲基氨基吡啶(10mg)處理粗混合物(2.46g,5.5mmol)于吡啶(23ml)中的溶液。攪拌溶液1.5h,然后用乙醚稀釋,并倒入裝有1N HCl溶液的分液漏斗中。攪動(dòng)并分離各層,有機(jī)層用飽和氯化鈉溶液洗滌,于無水硫酸鎂上干燥,并真空濃縮,得到2.6g黃色油狀物。通過柱層析純化粗品(40∶1硅膠/粗品;用5%-10%乙酸乙酯的己烷洗脫),得到1.1g(42%)乙酸酯靶化合物的單一異構(gòu)體;
1H NMR(300MHz,CDCl3)δ7.46-7.48(m,2H,2-ArH),7.31-7.39(m,2H,2-ArH),7.09(dt,J=2,8Hz,1H,3-ArH),6.98(brs,1H,C=CH),6.80(d,J=8Hz,1H,3-ArH),6.66(dd,J=2,8Hz,1H,3-ArH),6.56(t,J=8Hz,1H,3-ArH),4.94(d,J=1Hz,2H,CH2OAc),3.94(t,J=7Hz,2H,ArOCH2),2.04(s,3H,COCH3),1.78(quint,J=7Hz,2H,OCH2CH2),1.13-1.50(m,14H,7×CH2),and 0.86(t,J=7Hz,3H,CH3);13CNMR(75MHz,CDCl3)δ170.70(C=O),157.03(3-ArC),139.27,134.33,132.31,130.09,128.89,128.80,127.07,125.64(q,J3c,f=4Hz,2-ArC),124.59,124.06(q,J3c,f=4Hz,2-ArC),119.78,111.62,69.00,68.30,31.90,29.62,29.39,29.33,29.20,26.09,22.68,20.92,18.54,and 14.11;IR(film)2925,2855,1740(C=O),1450,1325,1245,1220,1165,and 1125cm-1;MS(DCI)m/e 477(MH+),476(M+).
用2N NaOH溶液(4.4ml,8.7mmol)處理乙酸酯(1.04g,2.18mmol)的甲醇(10.9ml)溶液,并回流攪拌2h。冷卻溶液至室溫,并倒入水中,用乙醚萃取。將氯化鈉加至水層,用乙醚第二次萃取。合并有機(jī)層,依次用水和飽和氯化鈉溶液洗滌,于無水硫酸鎂上干燥,過濾并濃縮,得到0.96g無色油狀物。通過柱層析純化(20∶1硅膠/粗產(chǎn)物;用5%-10%乙酸乙酯的已烷洗脫),得到0.87g(92%)產(chǎn)物(5n),為透明、無色油狀物;
1H NMR(300MHz,CDCl3)δ7.45-7.51(m,2H,2-ArH),7.31-7.40(m,2H,2-ArH),7.09(dt,J=2,8Hz,1H,3-ArH),6.95(brs,1H,C=CH),6.80(d,J=8Hz,1H,3-ArH),6.67(dd,J=2,8Hz,1H,3-ArH),6.56(t,J=8Hz,1H,3-ArH),4.52(dd,J=1,6Hz,2H,CH2OH),3.94(t,J=7Hz,2H,OCH2),1.78(quint,J=7Hz,2H,OCH2CH2),1.21-1.48(m,14H,7×CH2),0.87(t,J=7Hz,3H,CH3);13CNMR(75MHz,CDCl3)δ157.05(3-ArC),139.66,132.42,130.19,128.83,128.59,125.52(q,J3c,f=4Hz,2-ArC),124.98,124.49,123.95(q,J3c,f=4Hz,2-ArC),119.80,111.63,68.41,68.34,31.90,29.62,29.58,29.39,29.34,29.20,26.10,22.68,and 14.11;IR(film)3380(br,OH),2925,2855,1580,1325,1245,and 1125cm-1;MS(DCI)m/e 435(MH+),434(M+),417(MH+-H2O).
對(duì)于(Z)-2-(3-三氟甲苯基)-3-[4-(2E),(6E)-3,7-二甲基-辛-2,6-二烯氧]苯基)-2-丙烯醇(5o)量度=2.0mmol,產(chǎn)率=67%;
1H NMR(300MHz,CDCl3)δ7.52-7.54(m,2H,2-ArH),7.39-7.45(m,2H,2-ArH),6.86(d,J=8Hz,2H,3-ArH),6.63-6.68(m,3H,2×3-ArH and ArCH=C),5.41(dt,J=1,6.5Hz,1H,C=CHCH2O),5.03-5.06(m,1H,CH=C(CH3)2),4.40-4.45(m,4H,ArOCH2and CH2OH),2.02-2.10(m,4H,C=CHCH2CH2),and 1.56-1.68(m,9H,3×CH3);13CNMR(75MHz,CDCl3)δ158.14(3-ArC),141.22,139.85,137.67,132.56,131.81,130.93,130.41(3-ArC),129.20,128.09,125.61(q,J3c,f=4Hz,2-ArC),124.15,123.77,119.31,114.36(3-ArC),68.64(CH2OH),64.81(ArOCH2),39.50,26.27,25.66,17.67,and 16.62;IR(film)3360(br,OH),2970,2920,1605,1510,1325,1305,1245,1175,and 1165cm-1;MS(DCI)m/e 431(MH+),413(MH+-H2O).
對(duì)于(Z)-2-(3-三氟甲苯基)-3-(3,4-二癸氧苯基)-2-丙烯醇(5p)量度=2.37mmol,產(chǎn)率=93%;
1H NMR(300MHz,CDCl3)δ7.40-7.55(m,4H,2-ArH),6.66(d,J=8Hz,1H,3-ArH),6.65(d,J=2Hz,1H,3-ArH),6.57(dd,J=2,8Hz,1H,3-ArH),6.33(t,J=2Hz,1H,C=CH),4.43(dt,J=2,8Hz,CH2OH),3.90(t,J=7Hz,2H,CH2OAr),3.46(t,J=7Hz,2H,CH2OAr),1.69-1.79(m,2H,CH2CH2O),1.55-1.63(m,3H,CH2CH2O and OH),1.24-1.45(m,28H,14×CH2),0.83-0.89(m,6H,2×CH3);13CNMR(75MHz,CDCl3)δ148.47,148.32,140.22,137.68,132.69,131.50(q,J2c,f=38Hz,2-ArC),129.31,128.40,128.27,125.73(q,J3c,f=4Hz,2-ArC),124.07(q,J3c,f=4Hz,2-ArC),122.65,113.78,113.00,69.06(CH2O),68.69(CH2O),68.54(CH2O),31.91,29.59,29.57,29.33,29.18,29.01,25.97,25.82,22.69,and 14.11;IR(KBr)3400(br,OH),2960,2920,2850,1515,1475,1430,1330,1270,1235,1170,1140,1125,1100,1070,and 1020cm-1;MS(DCI)m/e 590(M+).
對(duì)于(Z)-2-(3-三氟甲苯基)-3-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2-丙烯醇(5q)量度=3.0mmol,得到1.14g目的化合物與雜質(zhì)的2∶1混合物。將乙酸酐(0.35g,3.5mmol)和4,4-二甲基氨基吡啶(10mg)加至該混合物(1.12g)于吡啶(11.6ml)中的攪拌溶液中,并于室溫?cái)嚢柙撊芤?h。用乙醚稀釋該溶液,并倒入1N HCl溶液中。攪拌并分離各層,用飽和氯化鈉溶液洗滌有機(jī)層,于無水硫酸鎂上干燥,并濃縮,得到1.14g淺黃色油狀物。通過柱層析純化(40∶1硅膠/粗產(chǎn)物;用3%-15%乙酸乙酯的己烷溶液進(jìn)行梯度洗脫),得到0.80g(20∶1Z∶E異構(gòu)體)乙酸酯。
1H NMR(300MHz,CDCl3)δ7.62(s,1H,ArH),7.54-7.58(m,3H,ArH),7.47(s,1H,ArH),7.37-7.40(m,3H,ArH),6.90(brs,1H,C=CH),6.77(dd,J=2,9Hz,1H,3-ArH),4.94(d,J=1Hz,2H,CH2OAc),2.05(s,3H,COCH3),1.72(s,4H,CH2CH2),and 1.33(brs,12H,4×CH3);13CNMR(75MHz,CDCl3)δ170.72(C=O),145.04,144.74,139.17,134.37,132.70,132.03,131.81,131.54,131.01,129.11,128.70,126.70,125.56,125.08,124.64,124.45,69.28(CH2OAc),34.99(CH2CH2),34.59,34.52,32.44(4×CH3),and 20.95(COCH3);IR(KBr)2960,2950,2925,1735,(C=O),1325,1255,1230,1160,and 1125cm-1;MS(DCI)m/e 481(MH+),480(M+),421(M+-OAc).
將該乙酸酯(0.77g,1.66mmol)溶于甲醇(8.3ml)和四氫呋喃(8.3ml),并用2N NaOH(3.33ml,6.66mmol)處理該攪拌溶液?;亓骷訜峄旌衔?.5h。冷卻至室溫,并倒入飽和氯化銨溶液中,用乙醚萃取。合并有機(jī)層,依次用水和飽和氯化鈉溶液洗滌,于無水硫酸鎂上干燥,并濃縮,得到0.74g透明、無色油狀物。通過柱層析純化(20∶1硅膠/粗產(chǎn)物;用10%-15%乙酸乙酯的己烷洗脫),得到0.69g(56%)丙烯醇5q,為淺黃色油狀物。
1H NMR(300MHz,CDCl3)δ7.63(s,1H,ArH),7.54-7.59(m,3H,ArH),7.47(s,1H,ArH),7.35-7.42(m,3H,ArH),6.89(s,1H,C=CH),6.80(dd,J=2,9Hz,1H,3-ArH),4.52(brs,2H,CH2OH),1.72(s,4H,CH2CH2),and 1.34(brs,12H,4×CH3);13CNMR(75MHz,CDCl3)δ144.80,144.67,139.61,139.21,132.80,132.46,131.62,131.30,130.89,129.16,128.82,128.36,126.66,125.75,125.50(q,J3c,f=4Hz,2-ArC),125.01,124.64,124.36(q,J3c,f=4Hz,2-ArC),122.22,68.52(CH2OH),35.01(CH2CH2),34.58,34.53,and 32.45(4×CH3);IR(film)3320(br,OH),2960,2930,1325,1165,and 1130cm-1;MS(DCI)m/e 439(MH+),421(MH+-H2O).
對(duì)于(Z)-2-(3-三氟甲苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-戊烯醇(5r)量度=1.84mmol,產(chǎn)率=87%;
1H NMR(300MHz,CDCl3)δ7.50(brd,J=8Hz,1H,2-ArH),7.37-7.42(m,3H,2-ArH),7.17(d,J=8Hz,5-ArH),6.99(d,J=2Hz,1H,5-ArH),6.83(dd,J=2,8Hz,1H,5-ArH),5.84(t,J=8Hz,1H,C=CH),4.29(s,2H,CH2OH),2.61(t,J=8Hz,2H,ArCH2),2.25(q,J=8Hz,2H,ArCH2CH2),1.64(brs,4H,CH2CH2),1.24(s,6H,2×CH3),and 1.22(s,6H,2×CH3);13CNMR(75MHz,CDCl3)δ144.68,142.48,139.56,139.30,138.08,132.03,130.50(q,J2c,f=32Hz,2-ArC),129.82,128.71,126.45,125.69,125.27(q,J3c,f=4Hz,2-ArC),123.91(q,J3c,f=4Hz,2-ArC),67.88(OCH2),35.54,35.14,35.09,34.13,33.93,31.87,31.81,and 30.74;IR(film)3320(br,OH),2960,2925,2860,1460,1365,1325,1310,1165,1130,1110,1070,805,and 705cm-1;MS(DCI)m/e 399(M+-OH).
對(duì)于(Z)-2-(4-氟苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-戊烯醇(5s)量度=2.91mmol,產(chǎn)率=68%;
1HNMR(300MHz,CDCl3)δ7.17(d,J=8Hz,1H,5-ArH),6.92-6.99(m,5H,4×2-ArH and 1×5-ArH),6.82(dd,J=2,8Hz,1H,5-ArH),5.76(t,J=8Hz,1H,C=CH),4.25(d,J=5.5Hz,2H,CH2OH),2.59(t,J=8Hz,2H,ArCH2),2.25(q,J=8Hz,2H,ArCH2CH2),1.64(brs,4H,CH2CH2),1.36(t,J=5.5Hz,1H,OH),1.24(s,6H,2×CH3),and 1.22(s,6H,2×CH3);13CNMR(75MHz,CDCl3)δ161.90(d,J1c,f=246Hz,2-ArC),144.62,144.40,139.82,138.28,134.16,130.16(d,J3c,f=8Hz,2-ArC),128.70,126.49,126.30,125.78,115.12(J2c,f=21Hz,2-ArC),68.12(CH2OH),35.58,35.15,35.10,34.13,33.94,31.90,31.85,and 30.45;IR(film)3300(br,OH),2960,2925,2860,1600,1510,1455,1385,1360,1220,and 835 cm-1;MS(DCI)m/e 349(M+-OH).
對(duì)于(Z)-2-(3-氟苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-戊烯醇(5t)量度=4.16mmol,產(chǎn)率=65%;
1H NMR(300MHz,CDCl3)δ7.16-7.28(m,2H,1×2-ArH and 1×5-ArH),6.99(d,J=2Hz,5-ArH),6.94(apparent tt,J=2,8Hz,1H,2-ArH),6.79-6.86(m,2H,1×5-ArH and 1×2-ArH),6.71(apparent dt,J=2,8Hz,1H,2-ArH),5.78(t,J=8Hz,1H,C=CH),4.26(d,J=5Hz,2H,CH2OH),2.61(t,J=8Hz,2H,ArCH2),2.28(q,J=8Hz,2H,ArCH2CH2)1.65(brs,4H,CH2CH2),1.40(t,J=5Hz,1H,OH),1.24(s,6H,2×CH3),and 1.23(s,6H,2×CH3);13CNMR(75MHz,CDCl3)δ162.64(d,J1c,f=246Hz,2-ArC),144.66,142.45,140.67(d,J3c,f=8Hz,2-ArC),139.73,138.21,129.69(d,J3c,f=8Hz,2-ArC),129.13,126.48,126.41,125.76,124.29(d,J4c,f=5Hz,2-ArC),115.52(J2c,f=21Hz,2-ArC),113.98(J2c,f=21Hz,2-ArC),67.92(CH2OH),35.55,35.15,35.10,34.15,33.95,31.89,31.84,and 30.48;IR(film)3300(br,OH),3020,2960,2925,2860,1610,1580,1490,1460,1435,1410,1385,1360,1260,1235,1220,1190,1090,1070,1005,890,825,785,760,720,and 700cm-1;MS(DCI)m/e 349(M+-OH).
對(duì)于(Z)-2-苯基-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-戊烯醇(5u)量度=1.10mmol,產(chǎn)率=74%;
1H NMR(300MHz,CDCl3)δ7.23-7.32(m,3H,2-ArH),7.16(d,J=8Hz,1H,5-ArH),7.00-7.07(m,3H,1×5ArH and 2×2ArH),6.84(dd,J=2,8Hz,1H,5-ArH),5.76(t,J=8Hz,1H,C=CH),4.29(s,2H,CH2OH),2.61(t,J=8Hz,2H,ArCH2),2.28(q,J=8Hz,2H,ArCH2CH2),1.66(brs,4H,CH2CH2),1.44(brs,1H,OH),1.24(s,6H,2×CH3),and 1.22(s,6H,2×CH3);13CNMR(75MHz,CDCl3)δ144.57,142.31,140.77,138.44,138.33,128.56,128.26,128.19,127.10,126.47,126.36,125.76,68.10(CH2OH),35.70,35.18,35.12,34.15,33.93,31.91,31.86,and 30.43;IR(film)3340(br,OH),2960,2925,2860,1495,1455,1440,1385,1360,1090,1070,1025,1000,825,760,and 700cm-1;MS(DCI)m/e 331(MH+-H2O).
對(duì)于(Z)-2-(3-三氟甲苯基)-5-[3-(1-金剛烷基)-4-羥苯基]-2-戊烯醇(5v)量度=1.4mmol,產(chǎn)率=81%;
1H NMR(300MHz,CDCl3)δ7.51(d,J=8Hz,1H,2-ArH),7.42(t,J=8Hz,1H,2-ArH),7.34(s,1H,2-ArH),7.23(d,J=7Hz,1H,2-ArH),6.90(d,J=2Hz,1H,5-ArH),6.73(dd,J=2,8Hz,1H,5-ArH),6.50(d,J=8Hz,1H,5-ArH),5.82(m,1H,C=CH),4.71(s,1H,ArOH),4.30(d,J=6Hz,2H,CH2OH),2.58(t,J=7Hz,2H,ArCH2),2.23(q,J=7Hz,2H,ArCH2CH2),2.07(brs,9H,adamantyl),1.75(s,6H,adamantyl),and 1.44(t,J=6Hz,1H,OH);13CNMR(75MHz,CDCl3)δ152.63,139.56,139.30,136.15,133.13,132.08,130.63(d,J2c,f=32Hz,2-ArC),129.89,128.72,127.18,126.32,125.26(d,J3c,f=4Hz,2-ArC),123.92(d,J3c,f=4Hz,2-ArC),116.61,67.92(CH2OH),40.55(adamantyl CH2),37.05(adamantyl CH2),36.58(adamantyl quaternary),35.27,30.76,and 29.02(adamantyl CH);IR(KBr)3430(OH),3250(br,OH),2900,1325,1170,1160,1125,1075,and 990cm-1;MS(DCI)m/e 456(M+),455(M-H)+,241,135(C10H15+).Anal.Calcd for C28H31F3O2C,73.66;H,6.84.FoundC,73.86;H,6.87.
對(duì)于(Z)-2-(3-三氟甲苯基)-5-[3-(1-金剛烷基)-4-甲氧苯基]-2-戊烯醇(5w)通過將(Z)-2-(3-三氟甲苯基)-5-[3-(1-金剛烷基)-4-羥苯基]-2-戊烯醇(5v)與硫酸二甲酯(0.25g,2.0mmol)和碳酸鉀(0.19g,1.3mmol)在回流的丙酮(10ml)中反應(yīng)6h制得。量度=0.87mmol,產(chǎn)率=78%;
1H NMR(300MHz,CDCl3)δ7.51(m,1H,2-ArH),7.42(t,J=8Hz,1H,2-ArH),7.35(s,1H,2-ArH),7.24(m,1H,2-ArH),6.92(m,1H,5-ArH),6.86(dd,J=2,8Hz,1H,5-ArH),6.74(d,J=8Hz,1H,5-ArH),5.84(m,1H,C=CH),4.30(m,2H,CH2OH),3.78(s,3H,OCH3),2.61(t,J=7Hz,2H,ArCH2),2.25(q,J=7Hz,2H,ArCH2CH2),2.04(brs,9H,adamantyl),1.75(s,6H,adamantyl),and 1.42(t,J=6Hz,1H,OH);13CNMR(75MHz,CDCl3)δ157.13,139.57,139.36,138.28,132.82,132.08,130.62(d,J2c,f=32Hz,2-ArC),129.91,128.71,126.82,126.25,125.91,125.27(d,J3c,f=4Hz,2-ArC),123.90(d,J3c,f=4Hz,2-ArC),111.61,67.92(CH2OH),55.04(OCH3),40.60(adamantyl CH2),37.13(adamantyl CH2),36.86(adamantyl quaternary),35.31,30.77,and 29.10(adamantyl CH);IR(film)3345(br,OH),2905,2850,1325,1235,1165,and 1130cm-1;MS(DCI)m/e 470(M+),469(MH)+,255,135(C10H15+).Anal.Calcd for C29H33F3O2:C,74.02;H,7.07.Found:C,73.96;H,7.05.
對(duì)于(Z)-2-苯基-5-[3-(1-金剛烷基)-4-甲氧苯基]-2-戊烯醇(2.5∶1,Z∶E)(5x)通過三個(gè)步驟得自(Z)-1-(叔丁基二甲基甲硅烷氧基)-2-苯基-5-[3-(1-金剛烷基)-4-叔丁基二甲基甲硅烷氧苯基]-2-戊烯,后者為合成7j過程中的副產(chǎn)物。將雙甲硅烷基醚(0.700g,1.14mmol)溶于30ml 3∶1∶1乙酸/THF/H2O中,并攪拌48h。真空除去溶劑,用1.1M四丁基氟化銨的THF(1.44ml,1.59mmol)溶液處理殘余物2-苯基-5-[3-(1-金剛烷基)-4-叔丁基二甲硅烷氧苯基]-2-戊烯醇(2.5∶1,Z∶E)的THF(10ml)溶液。于室溫?cái)嚢柙摶旌衔?0min,然后通過加入飽和氯化銨溶液(10ml)終止反應(yīng)。將該溶液在乙醚和水之間分配。分離有機(jī)相,于無水硫酸鎂上干燥,過濾,并濃縮,得到2-苯基-5-[3-(1-金剛烷基)-4-羥苯基]-2-戊烯醇(2.5∶1,Z∶E)1H NMR(300MHz,CDCl3)δ(Z-isomer)7.25-7.34(m,3H,2-ArH),7.09-7.12(m,2H,2-ArH),6.91(d,J=2Hz,1H,5-ArH),6.75(dd,J=8,2Hz,1H,5-ArH),6.49(d,J=8Hz,1H,5-ArH),5.75(t,J=7Hz,1H,C=CH),4.30(m,2H,CH2OH),2.58(t,J=7Hz,2H,ArCH2),2.28(q,J=7Hz,2H,ArCH2CH2),2.08(s,9H,adamantyl),and 1.73(s,6H,adamantyl);(E-isomer,partially obscured)7.40(m,1H,2-ArH),6.97(d,J=2Hz,1H,5-ArH),6.86(dd,J=2,8Hz,1H,5-ArH),6.51(d,J=8Hz,1H,5-ArH),5.91(t,J=8Hz,1H,C=CH),and 2.71(t,J=8Hz,2H,ArCH2);IR(KBr)3520(OH),3345(OH),2900,2850,1240,and 700cm-1;MS(DCI)m/e 389(MH+),388(M+),371,241,135(C10H15+);Anal.Calcd for C27H32O2·0.3CH3CO2CH2CH3:C,81.62;H,8.36.Found:C,81.62;H,8.32.
在回流的丙酮中用硫酸二甲酯(0.195g,1.55mmol)和粉化的碳酸鉀(0.214g,1.55mmol)處理2-苯基-5-[3-(1-金剛烷基)-4-羥苯基]-2-戊烯醇(2.5∶1,Z∶E,0.600g,1.55mmol)18h。反應(yīng)混合物冷卻后真空濃縮。于硅膠上通過柱層析純化殘余物(依次用二氯甲烷和5%甲醇/二氯甲烷洗脫),得到385mg(84%總產(chǎn)率)5x,為Z∶E的3∶1異構(gòu)體混合物。
1H NMR(300MHz,CDCl3)δ(Z-isomer)7.37-7.22(m,3H,2-ArH),7.12(m,2H,2-ArH),6.95(d,J=2Hz,1H,5-ArH),6.88(dd,J=8,2Hz,1H,5-ArH),6.77(d,J=8Hz,1H,5-ArH),5.78(t,J=7Hz,1H,C=CH),4.31(m,2H,CH2OH),3.79(s,3H,OCH3),2.58(t,J=7Hz,1H,ArCH2),2.32(q,J=7Hz,2H,ArCH2CH2),2.02(s,9H,adamantyl),and 1.76(s,6H,adamantyl);(E-isomer,partially obscured)7.41(m,1H,2-ArH),5.92(t,J=8Hz,1H,C=CH),and 2.73(t,J=8Hz,2H,ArCH2).
對(duì)于(Z)-2-(3-三氟甲苯基)-5-[4-(1-金剛烷基)-3-羥苯基]-2-戊烯醇(5y)量度=1.8mmol,產(chǎn)率=83%;
1H NMR(300MHz,CDCl3)δ7.51(m,1H,2-ArH),7.40(m,1H,2-ArH),7.35(s,1H,2-ArH),7.15(d,J=8Hz,1H,2-ArH),7.06(d,J=8Hz,1H,5-ArH),6.60(dd,J=2,8Hz,1H,5-ArH),6.36(d,J=2Hz,1H,5-ArH),5.80(m,1H,C=CH),5.00(s,1H,ArOH),4.28(m,2H,CH2OH),2.56(t,J=7Hz,2H,ArCH2),2.23(q,J=7Hz,2H,ArCH2CH2),2.08(brs,9H,adamantyl),and 1.75(s,6H,adamantyl);13C NMR(75MHz,CDCl3)δ154.34,139.88,139.58,139.23,134.18,132.09,130.62(d,J2c,f=32Hz,2-ArC),129.59,128.76,126.87,125.26(d,J3c,f=3Hz,2-ArC),124.09(q,J1c,f=271Hz,CF3),123.97(d,J3c,f=3Hz,2-ArC),120.63,116.92,67.79(CH2OH),40.62(adamantyl CH2),37.05(adamantyl CH2),36.38(adamantyl quaternary),34.85,30.11,and 29.03(adamantyl CH);IR(film)3500(OH),3280(br,OH),2910,2870,2850,1420,1320,1310,1165,1125,1085,and 1070cm-1;MS(DCI)m/e 455(M-H)+,135(C10H15+).Anal.Calcd for C28H31F3O2:C,73.66;H,6.84.Found:C,73.58;H,6.84.
對(duì)于(Z)-2-(3-三氟甲苯基)-5-[4-(1-金剛烷基)-3-甲氧苯基]-2-戊烯醇(5z)通過將(Z)-2-(3-三氟甲苯基)-5-[4-(1-金剛烷基)-3-羥苯基]-2-戊烯醇(5y)與硫酸二甲酯(0.25g,2.0mmol)和碳酸鉀(0.19g,1.3mmol)在回流的丙酮(10ml)中反應(yīng)56h制得。量度=1.3mmol,產(chǎn)率=82%;
1H NMR(300MHz,CDCl3)δ7.51(m,1H,2-ArH),7.40(m,2H,2-ArH),7.17(d,J=8Hz,1H,2-ArH),7.07(d,J=8Hz,1H,5-ArH),6.63(dd,J=2,8Hz,1H,5-ArH),6.55(d,J=2Hz,5-ArH),5.84(m,1H,C=CH),4.29(d,J=1Hz,2H,CH2OH),3.74(s,3H,OCH3),2.63(t,J=7Hz,2H,ArCH2),2.27(q,J=7Hz,2H,ArCH2CH2),2.05(brs,9H,adamantyl),1.74(brs,6H,adamantyl),and 1.47(brs,1H,OH);13C NMR(75MHz,CDCl3)δ158.72,139.85,139.72,139.30,136.26,132.08,130.61(d,J2c,f=32Hz,2-ArC),129.62,128.73,126.31,125.29(d,J3c,f=4Hz,2-ArC),124.10(q,J1c,f=271Hz,CF3),123.93(d,J3c,f=4Hz,2-ArC),120.29,111.94,67.83(CH2OH),54.85(OCH3),40.65(adamantyl CH2),37.14(adamantyl CH2),36.66(adamantyl quaternary),35.48,33.31,and 29.10(adamantyl CH);IR(film)3355(OH),2905,2850,1325,1250,1165,1130,1100,and 1070cm-1;MS(DCI)m/e 470(M+),469(M-H)+,135(C10H15+).Exact mass spectrum(FAB)Calcd for C29H34F3O2(MH+)471.2511.Found:471.2496.Anal.Calcd for C29H33F3O2·0.1CH2Cl2:C,72.96;H,6.99.Found:C,72.88;H,7.10.
對(duì)于(Z)-2-苯基-5-[4-(1-金剛烷基)-3-甲氧苯基]-2-戊烯醇(5aa)量度=3.82mmol,產(chǎn)率=91%;
1H NMR(300MHz,CDCl3)δ7.20-7.33(m,3H,2-ArH),7.03-7.07(m,3H,2×2-ArH and 1×5-ArH),6.64(dd,J=2,8Hz,1H,5-ArH),6.55(d,J=2Hz,1H,5-ArH),5.75(t,J=8Hz,1H,C=CH),4.29(s,2H,CH2OH),3.74(s,3H,OCH3),2.62(t,J=8Hz,2H,ArCH2),2.30(q,J=8Hz,2H,ArCH2CH2),2.03-2.08(m,9H,adamantyl),and 1.74(brs,6H,adamantyl);13C NMR(75MHz,CDCl3)δ158.68,140.92,140.22,138.33,136.10,128.59,128.26,128.01,127.11,126.20,120.32,112.01,68.06(CH2OH),54.89(OCH3),40.68,37.14,36.65,35.62,30.27,and 29.11;IR(film)3350(br,OH),2904,2848,1610,1494,1452,1412,1246,1162,1138,1102,1090,1042,1026,1002,808,760,and 702cm-1;MS(DCI)m/e 402(M+),385(M+-OH).
對(duì)于(Z)-2-(3-三氟甲苯基)-5-[2-(1-金剛烷基)-4-羥苯基]-2-戊烯醇(5bb)量度=0.48mmol,產(chǎn)率=88%;
1H NMR(300MHz,CDCl3)δ7.52(m,1H,2-ArH),7.43(m,2H,2-ArH),7.33(m,1H,2-ArH),6.93(d,J=8Hz,1H,5-ArH),6.82(d,J=3Hz,1H,5-ArH),6.62(dd,J=3,8Hz,1H,5-ArH),5.90(m,1H,C=CH),4.34(m,2H,CH2OH),3.74(s,3H,OCH3),2.90(m,2H,ArCH2),2.26(m,2H,ArCH2CH2),2.02(brs,3H,adamantyl),1.92(m,6H,adamantyl),1.73(m,6H,adamantyl),and 1.51(brs,1H,OH);13C NMR(75MHz,CDCl3)δ157.52,148.97,139.52,139.33,132.67,132.08,130.75(d,J2c,f=32Hz,2-ArC),129.59,128.78,125.17(d,J3c,f=4Hz,2-ArC),124.03(d,J3c,f=4Hz,2-ArC),113.02,109.90,67.83(CH2OH),55.08(OCH3),42.07(adamantyl CH2),37.85(adamantyl quaternary),36.77(adamantyl CH2),33.66,32.35,and 29.10(adamantyl CH);IR(film)3390(br,OH),2910,2850,1325,1165,1125,and 1070cm-1;MS(DCI)m/e 471(MH+),470(M+),469(M-H)+,255,135(C10H15+).
對(duì)于(Z)-2-(3-三氟甲苯基)-3-[4-(1-金剛烷基)-3-甲氧苯基]-2-丙烯醇(5cc)量度=2.48mmol,產(chǎn)率=90%;
1H NMR(300MHz,CDCl3)δ7.55(m,2H,2-ArH),7.45(m,2H,2-ArH),7.01(d,J=8Hz,1H,3-ArH),6.69(s,1H,C=CH),6.61(dd,J=2,8Hz,1H,3-ArH),6.32(d,J=2Hz,1H,3-ArH),4.44(d,J=5Hz,2H,CH2OH),3.34(s,3H,OCH3),1.98(s,9H,adamantyl),and 1.69(m,7H,6×adamantyl and OH);13C NMR(75MHz,CDCl3)δ158.22,140.17,139.08,138.14,134.07,132.56,131.23(d,J2c,f=32Hz,2-ArC),129.36,127.99,126.29,125.75(d,J3c,f=4Hz,2-ArC),124.16(d,J3c,f=4Hz,2-ArC),122.11,68.60(CH2OH),54.25(OCH3),40.42(adamantyl CH2),37.06(adamantyl CH2),36.83(adamantyl quaternary),and 29.01(adamantyl CH);IR(KBr)3385(br,OH),2905,2850,1325,1130,and 1070cm-1;MS(DCI)m/e 443(MH+),442(M+),441(M-H)+,135(C10H15+).Anal.Calcd for C27H29F3O2·0.3CH3CO2CH2CH3C,72.23;H,6.75.Found:C,72.37;H,6.59.
對(duì)于(Z)-2-(3-三氟甲苯基)-5-[4-(1-金剛烷基)-3-叔丁基二甲基甲硅烷氧苯基]-2-戊烯醇(5dd)量度=6.7mmol,產(chǎn)率=82%;
1H NMR(300MHz,CDCl3)δ7.51(m,1H,2-ArH),7.40(m,2H,2-ArH),7.19(d,J=8Hz,1H,2-ArH),7.07(d,J=8Hz,1H,5-ArH),6.61(dd,J=2,8Hz,1H,5-ArH),6.48(d,J=2Hz,1H,5-ArH),5.83(m,1H,C=CH),4.29(d,J=5Hz,2H,CH2OH),2.56(t,J=7Hz,2H,ArCH2),2.23(m,2H,ArCH2CH2),2.06(brs,9H,adamantyl),1.74(s,6H,adamantyl),1.43(m,1H,OH),0.99(s,9H,SiC(CH3)3),and 0.26(s,6H,Si(CH3)2);13C NMR(75MHz,CDCl3)δ154.50,139.76,139.43,139.28,137.17,132.07,130.88,129.50,128.75,126.88,125.24(d,J3c,f=4Hz,2-ArC),123.97(d,J3c,f=4Hz,2-ArC),120.38,119.15,67.85(CH2OH),40.46(adamantyl CH2),37.07(adamantyl CH2),36.52(adamantyl quaternary),35.16,30.32,29.04(adamantyl CH),26.39(SiC(CH3)3),18.90(SiC(CH3)3),and-3.42(Si(CH3)2);IR(film)3320(br,OH),2930,2905,2850,1325,1265,1255,1165,1130,855,and 835cm-1;MS(DCI)m/e 571(MH+),570(M+),569(M-H)+,135(C10H15+).Exact mass spectrum(FAB)Calcd for C34H45F3O2Si(M+)570.3141.Found 570.3122.
實(shí)施例5合成化合物6的一般方法在氬氣環(huán)境下將醇5(1當(dāng)量)的無水二氯甲烷(0.1-0.2M)溶液冷卻至-60~0℃。用叔丁基二甲基氯代甲硅烷(1.3當(dāng)量)一次性處理該溶液,然后加入4-二甲基氨基吡啶(0.05當(dāng)量)。滴加三乙胺(1.4當(dāng)量),并將反應(yīng)混合物于0~25℃攪拌2-5h。然后將混合物在乙醚和飽和氯化銨溶液之間分配,有機(jī)層用飽和氯化鈉溶液洗滌,于無水硫酸鎂上干燥,過濾,并濃縮。通過柱層析純化(20∶1硅膠/粗產(chǎn)物;用己烷至2%-4%乙酸乙酯的己烷洗脫),得到所需產(chǎn)物。
對(duì)于(Z)-1-(叔丁基二甲基甲硅烷氧基)-2-(3-溴苯基)-3-苯基-2-丙烯(6a)量度=2.62mmol,產(chǎn)率=96%;
1H NMR(300MHz,CDCl3)δ7.39(dt,J=2,8Hz,1H,2-ArH),7.35(t,J=2Hz,1H,2-ArH),7.06-7.24(m,5H,ArH),6.95-6.98(m,2H,ArH),6.70(t,J=2Hz,1H,C=CH),4.37(d,J=2Hz,2H,CH2OSi),0.92(s,9H,Si(C(CH3)3),and 0.07(s,6H,Si(CH3)2);13C NMR(75MHz,CDCl3)δ139.87,136.30,131.58,130.35,130.14,129.17,128.01,127.72,126.78,125.87,122.52,67.80(CH2O),29.71(SiC(CH3)3),25.91(SiC(CH3)3),and-5.34(Si(CH3)2);IR(film)2955,2930,2885,2855,1560,1472,1250,1125,1075,1005,880,840,780,750,and 695cm-1;MS(DCI)m/e 401/403(MH+,1∶1).
對(duì)于(Z)-1-(叔丁基二甲基甲硅烷氧基)-2-(3-溴苯基)-3-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-丙烯(6b)量度=5.41mmol,產(chǎn)率=98%;
1H NMR(300MHz,CDCl3)δ7.42(dt,J=2,8Hz,1H,2-ArH),7.38(t,J=2Hz,1H,2-ArH),7.09-7.24(m,3H,ArH),6.85(d,J=2Hz,1H,3-ArH),6.83(dd,J=2,8Hz,1H,3-ArH),6.63(s,1H,C=CH),4.38(s,2H,CH2OSi),1.60(brs,4H,CH2CH2),1.20(s,6H,2×CH3),0.98(s,6H,2×CH3),0.95(s,9H,Si(C(CH3)3),and 0.07(s,6H,Si(CH3)2).
對(duì)于(Z)-1-(叔丁基二甲基甲硅烷氧基)-2-(3-溴苯基)-3-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2-丙烯(6c)量度=2.3mmol,產(chǎn)率=97%;
1H NMR(300MHz,CDCl3)δ7.61(d,J=6Hz,2H,ArH),7.37-7.60(m,4H,ArH),7.08-7.15(m,2H,ArH),6.83-6.87(m,2H,ArH and C=CH),4.22(d,J=1Hz,2H,CH2OSi),1.73(s,4H,CH2CH2),1.27-1.30(m,12H,4×CH3),0.95(s,9H,SiC(CH3)3),and 0.10(s,6H,Si(CH3)2);13C NMR(75MHz,CDCl3)δ153.16,144.42,141.47,139.34,133.13,131.68,131.62,130.71,131.36,130.08,128.02,126.44,126.38,126.10,124.95,124.58,122.51,67.86(CH2OSi),35.07(CH2CH2),34.55,34.53,32.48(4×CH3),29.72,25.95(SiC(CH3)3),18.46(SiC(CH3)3)and -5.29(Si(CH3)2);IR(film)2955,2930,2860,1470,1360,1255,1125,and 1110cm-1;MS(DCI)m/e 563/561(MH+,1∶1),433/431(MH+-OTBDMS,1∶1).
對(duì)于(Z)-1-(叔丁基二甲基甲硅烷氧基)-2-(3-溴苯基)-3-(4-癸氧苯基)-2-丙烯(6d)量度=5.70mmol,產(chǎn)率=97%;
1H NMR(300MHz,CDCl3)δ7.35-7.41(m,2H,2-ArH),7.16(t,J=8Hz,1H,2-ArH),7.09(dt,J=2,8Hz,1H,2-ArH),6.88(d,J=8Hz,2H,3-ArH),6.61-6.66(m,3H,2×3-ArH and C=CH),4.34(d,J=1Hz,2H,CH2OSi),3.85(t,J=7Hz,2H,ArOCH2),1.71(quintet,J=7Hz,2H,ArOCH2CH2),1.20-1.42(m,14H,7×CH2),0.91(s,9H,Si(C(CH3)3),0.85(t,J=7Hz,3H,CH3)and 0.06(s,6H,Si(CH3)2);13C NMR(75MHz,CDCl3)δ158.02,141.74,137.65,131.69,130.35,130.19,130.17,128.62,127.83,125.61,122.54,114.00,68.08(CH2OSi),67.88(ArOCH2),31.89,29.72,29.56,29.38,29.32,29.23,26.02,25.91(SiC(CH3)3),22.69,18.43(SiC(CH3)3),14.13,and-5.40(Si(CH3)2);IR(film)2955,2930,2855,1605,1560,1510,1470,1300,1250,1180,1130,1110,1070,1025,1005,885,840,780,and 695cm-1;MS(DCI)m/e 559/561(MH+,1∶1).
對(duì)于(Z)-1-(叔丁基二甲基甲硅烷氧基)-2-(3-溴苯基)-3-(3,4-雙癸氧苯基)-2-丙烯(6e)量度=1.6mmol,產(chǎn)率=100%;
1H NMR(300MHz,CDCl3)δ7.37-7.40(m,2H,2-ArH),7.21(t,J=9Hz,1H,2-ArH),7.11(dt,J=1,9Hz,1H,2-ArH),6.66(d,J=8Hz,1H,3-ArH),6.59(dd,J=2,9Hz,1H,3-ArH6),6.58(brs,1H,C=CH),6.40(d,J=2Hz,1H,3-ArH),4.34(d,J=2Hz,2H,CH2OSi),3.90(t,J=7Hz,2H,ArC4OCH2),3.53(t,J=7Hz,2H,ArC3OCH2),1.75(quint,J=7Hz,2H,ArC4OCH2CH2),1.61(quint,J=7Hz,2H,ArC3OCH2CH2),1.11-1.40(m,28H,14×CH2),0.83-0.92(m,6H,2×CH3),0.91(s,9H,SiC(CH3)3),and 0.05(s,6H,Si(CH3)2);13C NMR(75MHz,CDCl3)δ148.24(3-ArC),148.11(3-ArC),142.01,137.80,131.92,130.19,130.12,129.07,127.85,125.86,122.51,113.90,113.04,69.09,68.61,68.16,31.93,31.91,29.65,29.60,29.57,29.37,29.22,29.05,25.98,25.91(SiC(CH3)3),22.69,18.43(SiC(CH3)3),14.12,and-5.35(Si(CH3)2);IR(film)2955,2925,2855,1515,1470,1270,1260,1240,1140,1085,and 1070cm-1;MS(DCI)m/e 717/715(MH+,1∶1).
對(duì)于(Z)-1-(叔丁基二甲基甲硅烷氧基)-2-(3-溴苯基)-5-苯基-2-戊烯(6f)量度=1.57mmol,產(chǎn)率=98%;
1H NMR(300MHz,CDCl3)δ7.39(dt,J=2,8Hz,1H,2-ArH),7.07-7.27(m,7H,3×2-ArH and 4×5-ArH),6.98(dt,J=2,8Hz,1H,5-ArH),5.75(tt,J=1.5,7.5Hz,1H,C=CH),4.25(d,J=1.5Hz,2H,CH2OSi),2.65(t,J=7.5Hz,2H,ArCH2),2.26(q,J=7.5Hz,2H,ArCH2CH2),0.87(s,9H,Si(C(CH3)3),and 0.00(s,6H,Si(CH3)2);13C NMR(75MHz,CDCl3)δ141.43,141.01,139.35,131.47,129.77,129.42,128.15,127.29,126.51,125.72,121.94,67.09(CH2OSi),35.82,30.16,25.77(SiC(CH3)3),18.27(SiC(CH3)3),and -5.52(Si(CH3)2);IR(film)3085,3060,3025,3030,2955,2930,2895,2855,1590,1560,1495,1470,1460,1455,1360,1255,1125,1090,1070,1050,1005,840,815,775,750,700,and 675cm-1;MS(FAB)m/e 429/431(M+,1∶1),373/375(M+-t-Bu).
對(duì)于(Z)-1-(叔丁基二甲基甲硅烷氧基)-2-(3-溴苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-戊烯(6g)量度=2.4mmol,產(chǎn)率=94%;
1H NMR(300MHz,CDCl3)δ7.35(ddd,J=1,2,8Hz,1H,2-ArH),7.23(t,J=2Hz,1H,2-ArH),7.18(d,J=8Hz,1H,2-ArH),7.13(t,J=8Hz,1H,2-ArH),7.01(d,J=2Hz,1H,5-ArH),6.84-6.91(m,2H,5-ArH),5.77(t,J=7Hz,1H,C=CH),4.22(d,J=1H,2H,CH2OSi),2.60(t,J=7Hz,2H,ArCH2),2.25(q,J=7Hz,2H,ArCH2CH2),1.65(s,4H,CH2CH2),1.25(s,6H,2×CH3),1.23(s,6H,2×CH3),0.87(s,9H,SiC(CH3)3),and 0.00(s,6H,Si(CH3)2);13C NMR(75MHz,CDCl3)δ144.58,142.27,141.22,139.19,138.43,131.63,129.84,129.55,127.44,127.13,126.45,126.37,125.80,122.03,67.27(CH2OSi),35.70,35.21,35.14,34.15,33.94,31.93,31.87,30.32,25.91(SiC(CH3)3),and 18.39(SiC(CH3)3);IR(film)2955,2930,2855,1470,1460,1125,840,and 775cm-1;MS(DCI)m/e 539/541(M-H)+,1∶1),Anal.Calcd for C31H45OSiBr:C,68.74;H,8.37.Found:C,69.02;H,8.34.
對(duì)于(2Z),(4E)-1-(叔丁基二甲基甲硅烷氧基)-2-(3-溴苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-己二烯(6h)量度=3.20mmol,產(chǎn)率=92%;
1H NMR(300MHz,CDCl3)δ7.45(d,J=2Hz,1H,2-ArH),7.39-7.43(m,1H,2-ArH),7.19-7.28(m,4H,2×2-ArH and 2×5-ArH),7.09(dd,J=2,8Hz,1H,5-ArH),6.80(dt,J=1.5,12Hz,1H,C=CH),6.45(brd,J=12Hz,1H,C=CH),4.46(d,J=1.5Hz,2H,CH2OSi),2.20(d,J=1.5Hz,3H,C=CCH3),1.67(brs,4H,CH2CH2),1.24(s,12H,4×CH3),0.93(s,9H,Si(C(CH3)3),and 0.09(s,6H,Si(CH3)2);IR(film)2955,2930,2860,1555,1495,1470,1460,1405,1390,1360,1255,1215,1190,1125,1070,1050,1030,885,840,780,700,and 680cm-1;MS(DCI)m/e 552/554(M+,1∶1),421/423(M+-OSi[C(CH3)3](CH3)2).
對(duì)于(Z)-1-(叔丁基二甲基甲硅烷氧基)-2-(3-溴苯基)-5-[4-(1-金剛烷基)-3-甲氧苯基]-2-戊烯(6i)量度=4.36mmol,產(chǎn)率=87%;
1H NMR(300MHz,CDCl3)δ7.33-7.36(m,1H,2-ArH),7.18(t,J=2Hz,1H,2-ArH),7.12(t,J=8Hz,1H,2-ArH),7.07(d,J=8Hz,1H,3-ArH),6.88(dt,J=2,8Hz,1H,2-ArH),6.63(d,J=8Hz,1H,3-ArH),6.56(d,J=1Hz,1H,3-ArH),5.75(t,J=8Hz,1H,C=CH),4.20(brs,2H,CH2OSi),3.76(s,3H,OCH3),2.60(t,J=8Hz,2H,ArCH2),2.24(q,J=8Hz,2H,ArCH2CH2),2.05(brs,9H,adamantyl),1.74(brs,6H,adamantyl),0.86(s,9H,SiC(CH3)3),and -0.10(s,6H,Si(CH3)2);13C NMR(75MHz,CDCl3)δ158.66,141.72,140.19,139.33,136.04,131.63,129.85,129.54,127.45,126.88,126.24,122.00,120.38,112.03,67.23,(CH2OSi),54.89(OCH3),37.16,36.64,35.63,30.22,29.12,25.89(SiC(CH3)3),18.38(SiC(CH3)3),and -5.39(Si(CH3)2);IR(film)2950,2930,2905,2850,1470,1460,1455,1410,1250,and 1125cm-1;MS(DCI)m/e 595(MH+),465/463(MH+-OTBDMS,1∶1).
對(duì)于(Z)-1-(叔丁基二甲基甲硅烷氧基)-2-(3-溴苯基)-5-[3-(1-金剛烷基)-4-叔丁基二甲基甲硅烷氧苯基]-2-戊烯(6j)量度=6.9mmol,產(chǎn)率=80%;約3∶1的Z∶E異構(gòu)體混合物,該化合物按改進(jìn)的Shreet,Betal,U.S.Patent 4,717,720,1/1988方法制得。
1H NMR(300MHz,CDCl3)δ(Z-isomer)7.36(dt,J=8,2Hz,1H,2-ArH),7.24(t,J=2Hz,1H,2-ArH),7.15(t,J=8Hz,1H,2-ArH),6.92-6.95(m,2H,2-ArH,and 5-ArH),6.77(dd,J=8,2Hz,1H,5-ArH),6.64(d,J=8Hz,1H,5-ArH),5.78(t,J=7Hz,1H,C=CH),4.22(d,J=1H,2H,CH2OSi),2.58(t,J=7Hz,2H,ArCH2),2.22(q,J=7Hz,2H,ArCH2CH2),2.05(m,9H,adamantyl),1.76(s,6H,adamantyl),1.01(s,9H,SiC(CH3)3),0.88(s,9H,SiC(CH3)3),0.31(s,6H,Si(CH3)2),and 0.00(s,6H,Si(CH3)2);(E-isomer)7.55(t,J=2Hz,1H,2-ArH),7.31(m,2H,2-ArH),7.14(t,J=8Hz,1H,2-ArH),7.01(d,J=2Hz,1H,5-ArH),6.86(dd,J=8,2Hz,1H,5-ArH),6.72(d,J=8Hz,1H,5-ArH),5.82(t,J=7Hz,1H,C=CH),4.34(s,2H,CH2OSi),2.68(t,J=7Hz,2H,ArCH2),2.52(q,J=7Hz,2H,ArCH2CH2),1.12(s,9H,SiC(CH3)3),0.82(s,9H,SiC(CH3)3),0.32(s,6H,Si(CH3)2),and 0.01(s,6H,Si(CH3)2).
對(duì)于(Z)-1-(叔丁基二甲基甲硅烷氧基)-2-(3-溴苯基)-3-(3,4-雙戊氧苯基)-2-丙烯(6k)量度=1.52mmol,產(chǎn)率=90%;
1H NMR(300MHz,CDCl3)δ7.37-7.41(m,2H,2-ArH),7.10-7.24(m,2H,2-ArH),6.67(d,J=8Hz,1H,3-ArH),6.59(dd,J=2,8Hz,1H,3-ArH),6.58(t,J=1.5Hz,1H,C=CH),6.41(d,J=2Hz,1H,3-ArH),4.35(d,J=1.5Hz,2H,CH2OSi),3.91(t,J=6.5Hz,2H,3-ArOCH2),3.53(t,J=6.5Hz,2H,3-ArOCH2),1.71-1.78(m,2H,3-ArOCH2CH2),1.57-1.65(m,2H,3-ArOCH2CH2),1.27-1.41(m,8H),0.86-0.93(m,15H,2×CH3and Si(C(CH3)3)and 0.06(Si(CH3)2);13C NMR(75MHz,CDCl3)δ148.22,148.09,142.00,137.80,131.91,130.21,130.12,129.07,127.86,125.85,122.51,113.86,113.00,69.06,(3-ArOCH2),68.57(3-ArOCH2),68.15(CH2OSi),29.70,28.90,28.71,28.05,25.91(SiC(CH3)3),22.45,22.40,18.43,(SiC(CH3)3),14.06,14.03,and -5.35(Si(CH3)3);IR(film)2955,2930,2860,1590,1560,1515,1470,1430,1390,1270,1240,1170,1140,1085,1070,1050,1030,1005,890,840,810,780,and 700cm-1;MS(DCI)m/e 575/577(MH+,1∶1),443/445(M+-OSi[C(CH3)3](CH3)2).
實(shí)施例6合成化合物7的一般方法方法A在氬氣環(huán)境下將芳基溴6(1當(dāng)量)的無水四氫呋喃(0.1-0.15M)溶液冷卻至-78℃,并用叔丁基鋰溶液(1.4-1.8M于戊烷,2.1當(dāng)量)。于-78℃攪拌淺黃色反應(yīng)混合物30min,并通過套管加至預(yù)冷至-78℃的氯代甲酸乙酯(1.5-3當(dāng)量)的無水THF溶液中。所得混合物溫?zé)嶂潦覝?,然后倒入裝有乙醚和飽和氯化銨溶液的分液漏斗中。攪拌并分離各層,用飽和氯化鈉溶液洗滌有機(jī)相,于無水硫酸鎂上干燥,過濾,并濃縮。通過柱層析純化(20∶1硅膠/粗產(chǎn)物;用1%-2%乙酸乙酯的己烷洗脫),得到所需產(chǎn)物。
方法B在氬氣環(huán)境下將芳基溴6(1當(dāng)量)的無水四氫呋喃溶液(0.1M)冷卻至-78℃,并用叔丁基鋰溶液(1.4-1.8M于戊烷,2當(dāng)量)處理。于-78℃攪拌反應(yīng)混合物30min,然后用無水二甲基甲酰胺(2當(dāng)量)處理。所得混合物加熱至室溫,然后倒入裝有乙醚和飽和氯化銨溶液的分液漏斗中,攪拌并分離各層,有機(jī)層用飽和氯化鈉溶液洗滌,于無水硫酸鎂上干燥,過濾并濃縮。粗醛(1當(dāng)量)溶于甲醇(0.1M溶液),并用氰化鈉(5.4當(dāng)量)、乙酸(數(shù)滴)和二氧化錳(5∶1重量化的MnO2/粗醛)處理。于室溫?cái)嚢杌旌衔?-14h,然后用二氯甲烷稀釋,并通過1英寸硅藻土塞過濾。濾液用水和飽和氯化鈉溶液洗滌,于無水硫酸鎂上干燥,過濾,濃縮。經(jīng)柱層析純化(20-40∶1硅膠/粗產(chǎn)物;用1%-2%乙酸乙酯的己烷洗脫),得到所需產(chǎn)物。
對(duì)于(Z)-1-(叔丁基二甲基甲硅烷氧基)-2-(3-乙氧羰基苯基)-3-苯基-2-丙烯(7a)通過方法A,量度=2.48mmol,產(chǎn)率=46%;
1H NMR(300MHz,CDCl3)δ7.93-7.96(m,1H,2-ArH),7.90(t,J=2Hz,1H,2-ArH),7.30-7.36(m,2H,2-ArH),7.04-7.10(m,3H,3-ArH),6.92-6.95(m,2H,3-ArH),6.73(t,J=2Hz,1H,C=CH),4.41(d,J=2Hz,2H,CH2OSi),4.34(q,J=7Hz,2H,CO2CH2),1.35(t,J=7Hz,3H,CO2CH2CH3),0.91(s,9H,Si(C(CH3)3),and 0.07(s,6H,Si(CH3)2);13C NMR(75MHz,CDCl3)δ166.50(C=O),140.44,139.41,136.46,133.73,130.84,129.70,129.17,128.62,128.49,127.97,126.66,125.81,67.89(CH2OSi),61.02(CO2CH2),25.91(SiC(CH3)3),18.42(SiC(CH3)3),14.30(CO2CH2CH3)and -5.34(Si(CH3)2);IR(film)2955,2930,2895,2855,1720,(C=O),1470,1465,1370,1265,1195,1125,1110,1080,1020,880,840,780,and 695cm-1;MS(FAB)m/e 395(M-H+).
對(duì)于(Z)-1-(叔丁基二甲基甲硅烷氧基)-2-(3-乙氧羰基苯基)-3-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-丙烯(7b)通過方法A,量度=4.77mmol,產(chǎn)率=73%;
1H NMR(300MHz,CDCl3)δ7.94-7.97(m,2H,2-ArH),7.36-7.38(m,2H,3-ArH),7.05(d,J=8Hz,1H,3-ArH),6.75-6.83(m,2H,3-ArH),6.64(brs,1H,C=CH),4.42(d,J=1.5Hz,2H,CH2OSi),4.33(q,J=7Hz,2H,CO2CH2),1.54(brs,4H,CH2CH2),1.34(t,J=7Hz,3H,CO2CH2CH3),1.19(s,3H,CH3),1.18(s,3H,CH3),0.98(s,6H,2×CH3),0.95(s,9H,Si(C(CH3)3),and 0.06(s,6H,Si(CH3)2);13C NMR(75MHz,CDCl3)δ166.54(C=O),144.20,143.57,140.00,139.30,133.79,133.26,130.87,129.94,128.67,128.34,127.30,126.67,126.16,126.10,68.28(CH2OSi),60.94(CO2CH2),34.96,33.98,33.86,31.67,31.42,27.93,25.91(SiC(CH3)3),18.42(SiC(CH3)3),14.31(CO2CH2CH3)and-5.33(Si(CH3)2);IR(film)2960,2930,2860,1720(C=O),1470,1460,1280,1260,1195,840,and 775cm-1;MS(DCI)m/e 506(M+).
對(duì)于(Z)-1-(叔丁基二甲基甲硅烷氧基)-2-(3-乙氧羰基苯基)-3-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2-丙烯(7c)通過方法A,量度=2.21mmol,產(chǎn)率=43%;
1H NMR(300MHz,CDCl3)δ7.94-7.98(m,2H,ArH),7.58(d,J=9Hz,2H,ArH),7.45(s,1H,ArH),7.27-7.36(m,3H,ArH),6.88(s,1H,C=CH),6.80(dd,J=2,9Hz,1H,ArH),4.47(d,J=1Hz,2H,CH2OSi),4.34(q,J=7Hz,2H,CO2CH2),1.72(s,4H,CH2CH2),1.29-1.38(m,15H,4×CH3and CO2CH2CH3),0.94(s,9H,SiC(CH3)3),and 0.10(s,6H,Si(CH3)2);13C NMR(75MHz,CDCl3)δ166.58(C=O),144.38,144.32,139.95,139.51,134.07,133.29,131.66,130.80,130.64,129.67,128.56,128.52,127.93,126.42,126.31,126.18,124.92,124.55,67.95(CH2OSi),61.02(CO2CH2),35.05,34.51,32.46,25.95(SiC(CH3)3),18.45(SiC(CH3)3),and 14.28;IR(film)2960,2930,2860,1720,(C=O),1470,1460,1365,1265,1190,1125,and 1110cm-1;MS(DCI)m/e 556(MH+),425(MH+-OTBDMS).
對(duì)于(Z)-1-(叔丁基二甲基甲硅烷氧基)-2-(3-甲氧羰基苯基)-3-(4-癸氧苯基)-2-丙烯(7d)量度=2.11mmol,產(chǎn)率=89%;
1H NMR(300MHz,CDCl3)δ7.92-8.01(m,2H,2-ArH),7.34-7.44(m,2H,2-ArH),6.87(d,J=8Hz,2H,3-ArH),6.60-6.67(m,3H,2×3-ArH and C=CH),4.41(d,J=1Hz,2H,CH2OSi),3.92(s,3H,CO2CH3),3.86(t,J=7Hz,2H,ArOCH2),1.72(quintet,J=7Hz,2H,ArOCH2CH2),1.20-1.42(m,14H,7×CH2),0.92(s,9H,Si(C(CH3)3),0.85(t,J=7Hz,3H,CH3)and 0.08(s,6H,Si(CH3)2);13C NMR(75MHz,CDCl3)δ166.92(C=O),157.78,139.75,138.05,134.33,133.89,131.38,130.84,130.33,130.20,129.71,128.56,128.26,125.40,113.95,68.01(CH2OSi),67.72(ArOCH2),52.00(CO2CH3),31.75,29.42,29.24,29.18,29.09,25.88,25.78(SiC(CH3)3),25.58,22.55,18.29(SiC(CH3)3),14.00,and -4.72(Si(CH3)2);IR(film)2950,2930,2855,1730(C=O),1605,1510,1470,1440,1390,1360,1290,1250,1200,1175,1110,1005,985,840,780,755,730,and 695cm-1;MS(DCI)m/e 538(M+).
對(duì)于(Z)-1-(叔丁基二甲基甲硅烷氧基)-2-(3-乙氧羰基苯基)-3-(3,4-雙癸氧苯基)-2-丙烯(7e)通過方法A,量度=1.29mmol,產(chǎn)率=44%;
1H NMR(300MHz,CDCl3)δ7.92-7.96(m,2H,2-ArH),7.36-7.37(m,2H,2-ArH),6.63(d,J=8Hz,1H,3-ArH),6.57(brs,1H,C=CH),6.55(dd,J=2,8Hz,1H,3-ArH),6.38(d,J=2Hz,1H,3-ArH),4.39(d,J=2Hz,2H,CH2OSi),4.34(q,J=6Hz,2H,CO2CH2),3.89(t,J=7Hz,2H,ArC4OCH2),3.48(t,J=7Hz,2H,ArC3OCH2),1.73(quint,J=7Hz,2H,ArC4OCH2CH2),1.54-1.59(m,2H,ArC3OCH2CH2),1.36(t,J=6Hz,3H,CO2CH2CH3),1.19-1.38(m,28H,14×CH2),0.83-0.90(m,15H,2×CH3and SiC(CH3)3)and 0.06(s,6H,Si(CH3)2);13C NMR(75MHz,CDCl3)δ166.42(C=O),148.15(3-ArC),148.00(3-ArC),140.01,138.39,133.93,130.90,129.97,129.22,128.63,128.30,125.81,122.40,114.06,112.99,69.04,68.57,68.25,61.00(CH2OSi),31.90,29.60,29.40,29.36,29.22,29.01,25.98,25.91(SiC(CH3)3),25.85,24.14,24.03,22.68,18.42(SiC(CH3)3),14.30,14.12,and -5.34(Si(CH3)2);IR(film)2955,2925,2855,1720(C=O),1515,1470,1265,1240,1140,1085,and 1020cm-1;MS(FAB)m/e 709(MH+).
對(duì)于(Z)-1-(叔丁基二甲基甲硅烷氧基)-2-(3-乙氧羰基苯基)-5-苯基-2-戊烯(7f)通過方法A,量度=1.51mmol,產(chǎn)率=52%;
1H NMR(300MHz,CDCl3)δ7.94(dt,J=2,8Hz,1H,2-ArH),7.82(t,J=2Hz,1H,2-ArH),7.34(t,J=8Hz,1H,2-ArH),7.08-7.26(m,6H,1×2-ArH and 5×5-ArH),5.80(tt,J=1.5,7.5Hz,1H,C=CH),4.38(q,J=7Hz,2H,CO2CH2),4.28(d,J=1.5Hz,2H,CH2OSi),2.67(t,J=7.5Hz,2H,ArCH2),2.26(q,J=7.5Hz,2H,ArCH2CH2),1.40(t,J=7Hz,3H,CO2CH2CH3),0.88(s,9H,Si(C(CH3)3),and 0.02(s,6H,Si(CH3)2);13C NMR(75MHz,CDCl3)δ166.50(C=O),141.53,139.75,139.09,133.17,130.21,129.60,128.36,128.10,127.95,126.51,125.66,67.21(CH2OSi),60.83,(CO2CH2),35.87,30.17,25.78(SiC(CH3)3),18.26(SiC(CH3)3),14.22(CO2CH2CH3),and -5.52(Si(CH3)2);IR(film)3085,3065,3030,2955,2930,2895,2855,1720(C=O),1470,1460,1455,1365,1270,1170,1125,1110,1085,1050,1030,840,815,775,755,700,and 675cm-1;MS(DCI)m/e 425(MH+).293(M+-OSi[(C(CH3)3](CH3)2).
對(duì)于(Z)-1-(叔丁基二甲基甲硅烷氧基)-2-(3-甲氧羰基苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-戊烯(7g)量度=1.40mmol,產(chǎn)率=100%;
1H NMR(300MHz,CDCl3)δ7.92(dt,J=1,8Hz,1H,2-ArH),7.85(t,J=1Hz,1H,2-ArH),7.33(t,J=8Hz,1H,2-ArH),7.12-7.17(m,2H,2-ArH and 5-ArH),7.01(d,J=2Hz,1H,5-ArH),6.84(dd,J=2,8Hz,1H,5-ArH),5.81(brt,J=7Hz,1H,C=CH),4.36(q,J=7Hz,2H,CO2CH2),4.28(d,J=1Hz,2H,CH2OSi),2.60(t,J=8Hz,2H,ArCH2),2.24(q,J=8Hz,2H,ArCH2CH2),1.64(s,4H,CH2CH2),1.38(t,J=7Hz,3H,CO2CH2CH3),1.24(s,6H,2×CH3),1.22(s,6H,2×CH3),0.87(s,9H,SiC(CH3)3),and 0.00(s,6H,Si(CH3)2);13C NMR(75MHz,CDCl3)δ166.64(C=O),144.56,142.23,139.63,139.28,138.54,133.35,130.28,129.75,128.04,127.06,126.40,126.33,125.76,67.39(CH2OSi),60.94(CO2CH2),35.74,35.20,35.13,34.13,33.92,31.91,31.85,30.34,25.91(SiC(CH3)3),18.39(SiC(CH3)3),14.35(CO2CH2CH3),and -5.36(Si(CH3)2);IR(film)2955,2930,2860,1720(C=O),1270,1120,1110,and 840cm-1;MS(FAB)m/e 534(M+),533(M-H)+.Anal.Calcd for C34H50O3Si:C,76.35;H,9.42.Found:C,76.78;H,9.40.
對(duì)于(2Z),(4E)-1-(叔丁基二甲基甲硅烷氧基)-2-(3-乙氧羰基苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-己二烯(7h)通過方法A,量度=2.04mmol,產(chǎn)率=34%;
1H NMR(300MHz,CDCl3)δ7.95(d,J=2Hz,1H,2-ArH),7.94(dt,J=2,8Hz,1H,2-ArH),7.36-7.45(m,2H,2-ArH),7.22(d,J=2Hz,1H,5-ArH),7.15(d,J=8Hz,1H,5-ArH),7.04(dd,J=2,8Hz,1H,5-ArH),6.80(brd,J=12Hz,1H,C=CH),6.37(brd,J=12Hz,1H,C=CH),4.46(s,2H,CH2OSi),4.35(q,J=7Hz,2H,CO2CH2),2.20(s,3H,C=CCH3),1.62(brs,4H,CH2CH2),1.36(t,J=7Hz,3H,CO2CH2CH3),1.20(s,6H,2×CH3),1.19(s,6H,2×CH3),0.91(s,9H,Si(C(CH3)3),and 0.07(s,6H,Si(CH3)2);13C NMR(75MHz,CDCl3)δ166.56(C=O),144.48,143.88,140.48,140.42,139.07,137.49,133.76,130.42,129.92,128.35,128.11,126.31,123.77,123.06,123.00,122.60,67.14(CH2OSi),60.98(CO2CH2),35.12,35.00,34.24,34.04,31.74,25.90(SiC(CH3)3),18.36(SiC(CH3)3),16.00(C=CCH3),14.32(CO2CH2CH3),and -5.32(Si(CH3)2);IR(film)2960,2930,2860,1720(C=O),1470,1460,1390,1365,1260,1215,1110,1085,840,780,and 755cm-1;MS(DCI)m/e 546(M+),415(M+-OSi[(C(CH3)3](CH3)2).
對(duì)于(Z)-1-(叔丁基二甲基甲硅烷氧基)-2-(3-甲氧羰基苯基)-5-[4-(1-金剛烷基)-3-甲氧苯基]-2-戊烯(7i)通過方法B,量度=3.81mmol,產(chǎn)率=25%;
1H NMR(300MHz,CDCl3)δ7.91(dt,J=2,8Hz,1H,2-ArH),7.83(t,J=2Hz,1H,2-ArH),7.31(t,J=8Hz,1H,2-ArH),7.14(dt,J=2,8Hz,1H,2-ArH),7.04(d,J=8Hz,1H,3-ArH),6.63(dd,J=2,8Hz,1H,3-ArH),6.55(d,J=2Hz,1H,3-ArH),5.79(brt,J=8Hz,1H,C=CH),4.26(d,J=2Hz,2H,CH2OSi),3.90(s,3H,CO2CH3),3.73(s,3H,OCH3),2.60(t,J=8Hz,2H,ArCH2),2.24(q,J=8Hz,2H,ArCH2CH2),2.04(brs,9H,adamantyl),1.74(brs,6H,adamantyl),0.86(s,9H,SiC(CH3)3),and -0.01(s,6H,Si(CH3)2);13C NMR(75MHz,CDCl3)δ137.11(C=O),158.64,140.29,139.67,139.30,136.01,133.50,129.92,129.78,128.08,126.87,126.20,120.34,112.00,67.32,(CH2OSi),54.86,(OCH3),52.09(CO2CH3),40.67,37.15,36.62,35.65,30.20,29.11,25.88,(SiC(CH3)3),and 18.38(SiC(CH3)3);IR(film)2950,2930,2905,2850,1725,(C=O),1460,1455,1440,1410,1280,1260,1160,and 1120cm-1;MS(DCI)m/e 575(MH+),574(M+),573(M-H)+,and 443(MH+-OSi[(C(CH3)3](CH3)2).
對(duì)于(Z)-1-(叔丁基二甲基甲硅烷氧基)-2-(3-乙氧羰基苯基)-5-[3-(1-金剛烷基)-4-叔丁基二甲基甲硅烷氧苯基]-2-戊烯(7j)通過方法A,量度=3.6mmol,經(jīng)硅膠柱層析后,得到1.6g 7j(3∶1,Z∶E)和1-(叔丁基二甲基甲硅烷氧基)-2-苯基-5-[3-(1-金剛烷基)-4-叔丁基二甲基甲硅烷氧苯基]-2-戊烯(3∶1,Z∶E)的1∶1混合物。收集各個(gè)分離級(jí)分并濃縮,得到0.800g(36%)后一種化合物1-(叔丁基二甲基甲硅烷氧基)-2-苯基-5-[3-(1-金剛烷基)-4-叔丁基二甲基甲硅烷氧苯基]-2-戊烯(3∶1,Z∶E)1H NMR(300MHz,CDCl3)δ(Z-isomer)7.20-7.32(m,3H,2-ArH),7.04-7.07(m,2H,2-ArH),6.94(d,J=2Hz,1H,5-ArH),6.77(dd,J=2,8Hz,1H,5-ArH),6.66(d,J=8Hz,1H,5-ArH),5.77(t,J=7Hz,1H,C=CH),4.28(d,J=1H,2H,CH2OSi),2.58(t,J=7Hz,2H,ArCH2),2.26(q,J=7Hz,2H,ArCH2CH2),2.08(m,9H,adamantyl),1.76(s,6H,adamantyl),1.03(s,9H,SiC(CH3)3),0.89(s,9H,SiC(CH3)3),0.32(s,6H,Si(CH3)2),and 0.02(s,6H,Si(CH3)2);(E-isomer,partially obscured)7.40(m,1H,2-ArH),6.90(dd,J=2,8Hz,1H,5-ArH),6.72(d,J=8Hz,1H,5-ArH),5.88(t,J=7Hz,1H,C=CH),4.41(s,2H,CH2OSi),2.69(t,J=7Hz,2H,ArCH2),1.04(s,9H,SiC(CH3)3),0.84(s,9H,SiC(CH3)3),0.34(s,6H,Si(CH3)2),and 0.02(s,6H,Si(CH3)2);IR(film) 2955,2930,2905,2855,1490,1255,and 840cm-1;MS(FAB)m/e 617(MH+),616(M+).Anal.Calcd for C39H60O2Si2:C,75.91;H,9.80.Found:C,75.62;H,9.77.
對(duì)于(Z)-1-(叔丁基二甲基甲硅烷氧基)-2-(3-甲氧羰基苯基)-3-(3,4-雙戊氧苯基)-2-丙烯(7k)通過方法B,量度=1.33mmol,產(chǎn)率=84%;
1H NMR(300MHz,CDCl3)δ7.91-7.95(m,2H,2-ArH),7.36-7.38(m,2H,2-ArH),6.63(d,J=8Hz,1H,3-ArH),6.62(brs,J=1.5Hz,1H,C=CH),6.56(dd,J=2,8Hz,1H,3-ArH),6.37(d,J=2Hz,1H,3-ArH),4.35(d,J=1.5Hz,2H,CH2OSi),3.89(t,J=6.5Hz,2H,ArOCH2),3.88(s,3H,CO2CH3),3.47(t,J=6.5Hz,2H,ArOCH2),1.70-1.79(m,2H,ArOCH2CH2),1.55-1.60(m,2H,ArOCH2CH2),1.24-1.41(m,8H,2×CH2),0.85-0.91(m,15H,2×CH3and Si(C(CH3)3),and 0.05(Si(CH3)2);13C NMR(75MHz,CDCl3)δ166.89(C=O),148.15,148.00,140.09,138.34,134.08,130.57,130.01,129.20,128.69,128.33,125.81,122.42,114.03,112.97,69.01(ArOCH2),68.53(CH2OSi),68.19(ArOCH2),52.11(CO2CH3),28.89,28.66,28.15,28.01,25.91(SiC(CH3)3),22.44,22.36,18.42,(SiC(CH3)3),14.02 and -5.34(Si(CH3)2);IR(film)2955,2930,2860,1725(C=O),1515,1470,1435,1265,1205,1170,1140,1080,1050,1005,840,and 780cm-1;MS(DCI)m/e 554(MH+),423(M+-OSi[C(CH3)3](CH3)2).
實(shí)施例7合成化合物8的一般方法將酯7溶于乙酸/四氫呋喃/水(3∶2∶1,0.03M)的混合物中,并于室溫下攪拌12-40h。然后真空濃縮混合物,殘余物通過柱層析純化(20∶1-30∶1硅膠/粗產(chǎn)物;用10%-20%乙酸乙酯的己烷洗脫)。
對(duì)于(Z)-2-(3-乙氧羰基苯基)-3-苯基-2-丙烯醇(8a)量度=1.09mmol,產(chǎn)率=94%;
1H NMR(300MHz,CDCl3)δ7.93-7.98(m,2H,2-ArH),7.34-7.38(m,2H,2-ArH),7.07-7.10(m,3H,3-ArH),6.93-6.98(m,2H,3-ArH),6.73(s,1H,C=CH),4.47(d,J=5Hz,2H,CH2OH),4.34(q,J=7Hz,2H,CO2CH2),1.73(t,J=5Hz,1H,OH,exch),and 1.35(t,J=7Hz,3H,CO2CH2CH3);13C NMR(75MHz,CDCl3)δ166.42(C=O),140.45,138.90,136.03,133.74,131.06,129.55,129.22,128.83,128.73,128.07,127.42,127.04,68.37(CH2OH),61.09(CO2CH2),and 14.30(CO2CH2CH3);IR(film)3400(br,OH),2980,1720,1370,1265,1195,1110,1090,1022,760,and 700cm-1;MS(DCI)m/e 282(MH+).
對(duì)于(Z)-2-(3-乙氧羰基苯基)-3-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-丙烯醇(8b)量度=3.35mmol,產(chǎn)率=91%;
1H NMR(300MHz,CDCl3)δ7.94-7.99(m,2H,2-ArH),7.37-7.44(m,2H,ArH),7.05(d,J=8Hz,1H,3-ArH),6.86(d,J=2Hz,1H,3-ArH),6.76(dd,J=2,8Hz,1H,3-ArH),6.65(s,1H,C=CH),4.45(s,2H,CH2OH),4.33(q,J=7Hz,2H,CO2CH2),1.51-1.59(m,5H,CH2CH2and OH,exch),1.32(t,J=7Hz,3H,CO2CH2CH3),1.17(s,6H,2×CH3),and 0.93(s,6H,2×CH3);13C NMR(75MHz,CDCl3)δ166.42(C=O),144.35,144.05,139.47,139.26,133.71,132.83,131.13,129.76,128.92,128.58,127.76,127.47,126.63,126.28,68.78(CH2OH),61.02(CO2CH2),34.92,34.03,33.88,31.65,31.44,27.92,and 14.32(CO2CH2CH3);IR(film)3100-3400(br,OH),2960,2925,2860,1720(C=O),1460,1365,1285,1265,1200,1110,1085,755,and 750cm-1;MS(DCI)m/e 392(M+),375(M+-OH).
對(duì)于(Z)-2-(3-乙氧羰基苯基)-3-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2-丙烯醇(8c)量度=0.95mmol,產(chǎn)率=97%;
1H NMR(300MHz,CDCl3)δ7.95-7.99(m,2H,2-ArH),7.59(d,J=12Hz,2H,ArH),7.47(s,1H,ArH),7.29-7.40(m,3H,ArH),6.88(brs,1H,C=CH),6.82(dd,J=1,9Hz,1H,ArH),4.53(dd,J=1,6Hz,2H,CH2OH),4.34(q,J=7Hz,2H,CO2CH2),1.72(s,4H,CH2CH2),and 1.31-1.36(m,15H,4×CH3and CO2CH2CH3);13C NMR(75MHz,CDCl3)δ166.47(C=O),144.62,144.55,139.96,138.98,134.08,132.84,131.64,131.08,130.81,129.53,128.76,128.22,128.08,126.58,125.98,124.98,124.56,68.52(CH2OH),61.07(CO2CH2),35.04(CH2CH2),34.56,34.52,32.46(4×CH3),and 14.27(CO2CH2CH3);IR(KBr)3400(br,OH),2960,2930,2860,1720,(C=O),1465,1385,1365,1270,1210,1190,1110,1085,and 1020cm-1;MS(DCI)m/e 443(MH+),425(MH+-OH).
對(duì)于(Z)-2-(3-乙氧羰基苯基)-3-(4-癸氧苯基)-2-丙烯醇(8d)量度=1.86mmol,產(chǎn)率=94%;
1H NMR(300MHz,CDCl3)δ7.96-8.00(m,2H,2-ArH),7.34-7.43(m,2H,2-ArH),6.88(d,J=8Hz,2H,3-ArH),6.67(s,1H,C=CH),6.63(d,J=8Hz,2H,3-ArH),4.46(brs,2H,CH2OH),3.90(s,3H,CO2CH3),3.86(t,J=7Hz,2H,ArOCH2),1.72(quintet,J=7Hz,2H,ArOCH2CH2),1.20-1.45(m,14H,7×CH2),and 0.87(t,J=7Hz,3H,CH3);13C NMR(75MHz,CDCl3)δ166.96(C=O),158.22,139.39,138.19,133.98,130.78,130.45,129.69,128.92,128.64,128.25,127.39,114.05,68.74(CH2OH),67.88(ArOCH2),52.19(CO2CH3),31.89,29.56,29.37,29.31,29.21,26.01,22.69,and 14.14;IR(film)3400(br,OH),2925,2855,1725(C=O),1605,1510,1470,1440,1390,1290,1270,1250,1200,1180,1110,1090,1020,980,885,825,755,710,and 700cm-1;MS(DCI)m/e 424(M+),407(M+-OH).
對(duì)于(Z)-2-(3-乙氧羰基苯基)-3-(3,4-雙癸氧苯基)-2-丙烯醇(8e)量度=0.53mmol,產(chǎn)率=96%;
1H NMR(300MHz,CDCl3)δ7.94-7.97(m,2H,2-ArH),7.33-7.43(m,2H,2-ArH),6.63(d,J=8Hz,1H,3-ArH),6.62(s,1H,C=CH),6.56(dd,J=2,8Hz,1H,3-ArH),6.40(d,J=2Hz,1H,3-ArH),4.44(d,J=6Hz,2H,CH2OH),4.34(q,J=7Hz,2H,CO2CH2),3.89(t,J=7Hz,2H,ArC4OCH2),3.49(t,J=7Hz,2H,ArC3OCH2),1.74(quint,J=7Hz,2H,ArC4OCH2CH2),1.55-1.61(m,2H,ArC3OCH2CH2),1.36(t,J=7Hz,3H,CO2CH2CH3),1.21-1.38(m,28H,14×CH2),and 0.83-0.89(m,6H,2×CH3);13C NMR(75MHz,CDCl3)δ166.32(C=O),148.32(3-ArC),148.20(3-ArC),139.50,138.32,133.87,131.17,129.79,128.87,128.68,128.54,127.54,122.53,114.06,112.93,69.01,68.76,68.61,61.07(CO2CH2),31.91,29.60,29.34,29.19,28.99,25.97,25.85,22.68,14.30,and 14.12;IR(KBr)3500(br,OH),2960,2920,2850,1720(C=O),1705(C=O),1515,1295,1265,1235,and 1140cm-1;MS(FAB)m/e 595(MH+).
對(duì)于(Z)-2-(3-乙氧羰基苯基)-5-苯基-2-戊烯醇(8f)量度=0.78mmol,產(chǎn)率=99%;
1H NMR(300MHz,CDCl3)δ7.95(dt,J=2,8Hz,1H,2-ArH),7.83(t,J=2Hz,1H,2-ArH),7.39(t,J=8Hz,1H,2-ArH),7.07-7.27(m,6H,1×2-ArH and 5×5-ArH),5.81(t,J=7.5Hz,1H,C=CH),4.37(q,J=7Hz,2H,CO2CH2),4.28(s,2H,CH2OH),2.67(t,J=7.5Hz,2H,ArCH2),2.31(q,J=7.5Hz,2H,ArCH2CH2),and 1.39(t,J=7Hz,3H,CO2CH2CH3);13C NMR(75MHz,CDCl3)δ166.40(C=O),141.27,140.12,138.53,133.01,130.48,129.43,128.57,128.31,128.24,128.17,125.78,67.73(CH2OH),60.93(CO2CH2),35.73,30.26,and 14.22(CO2CH2CH3);IR(film)3420(br,OH),3085,3060,3025,2980,2930,2860,1720(C=O),1495,1455,1390,1370,1280,1225,1170,1110,1085,1020,1000,755,700,and 675cm-1;MS(DCI)m/e 311(MH+),293(M+-OH).
對(duì)于(Z)-2-(3-乙氧羰基苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-戊烯醇(8g)量度=1.3mmol,產(chǎn)率=84%;
1H NMR(300MHz,CDCl3)δ7.94(d,J=8Hz,1H,2-ArH),7.88(s,1H,2-ArH),7.36(t,J=8Hz,1H,2-ArH),7.15-7.28(m,2H,2-ArH and 5-ArH),7.00(s,1H,5-ArH),6.84(d,J=8Hz,1H,5-ArH),5.83(t,J=7Hz,1H,C=CH),4.32-4.40(m,4H,CO2CH2CH3and CH2OH),2.64(t,J=7Hz,2H,ArCH2),2.27(q,J=7Hz,ArCH2CH2),1.65(s,4H,CH2CH2),1.38(t,J=7Hz,3H,CO2CH2CH3),1.24(s,6H,2×CH3),and 1.22(s,6H,2×CH3);13C NMR(75MHz,CDCl3)δ166.54(C=O),144.63,142.38,139.99,138.76,138.31,133.20,130.55,129.58,129.35,129.08,128.33,126.42,125.72,67.85(CH2OH),61.03(CO2CH2CH3),35.66,35.18,35.12,34.14,33.94,31.91,31.86,30.51,and 14.36(CO2CH2CH3);IR(film)3410(OH),2960,2925,2860,1720(C=O),1270,1025,and 755cm-1;MS(DCI)m/e 421(MH+),403,201;Exact mass spectrum(FAB)Calcd for C28H36O3Na(MNa+):443.2562,F(xiàn)ound:443.2544.
對(duì)于(2Z),(4E)-2-(3-乙氧羰基苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-己二烯醇(8h)量度=0.64mmol,產(chǎn)率=93%;
1H NMR(300MHz,CDCl3)δ8.04(d,J=2Hz,1H,2-ArH),7.99(dt,J=2,8Hz,1H,2-ArH),7.52(dt,J=2,8Hz,1H,2-ArH),7.44(t,J=8Hz,1H,2-ArH),7.25(d,J=2Hz,1H,5-ArH),7.20(d,J=8Hz,1H,5-ArH),7.10(dd,J=2,8Hz,1H,5-ArH),6.80(brd,J=12Hz,1H,C=CH),6.37(brd,J=12Hz,1H,C=CH),4.46(brd,J=6Hz,2H,CH2OH),4.39(q,J=7Hz,2H,CO2CH2),2.23(s,3H,C=CCH3),1.65(brs,4H,CH2CH2),1.39(t,J=7Hz,3H,CO2CH2CH3),1.25(t,J=6Hz,1H,OH),1.23(s,6H,2×CH3),and 1.21(s,6H,2×CH3).
對(duì)于(Z)-2-(3-甲氧羰基苯基)-5-[4-(1-金剛烷基)-3-甲氧苯基]-2-戊烯醇(8i)量度=0.96mmol,產(chǎn)率=98%;
1H NMR(300MHz,CDCl3)δ7.93(dt,J=2,8Hz,1H,2-ArH),7.86(t,J=2Hz,1H,2-ArH),7.37(t,J=8Hz,1H,2-ArH),7.19(dt,J=2,8Hz,1H,2-ArH),7.05(d,J=8Hz,1H,3-ArH),6.62(dd,J=2,8Hz,1H,3-ArH),6.54(d,J=2Hz,1H,3-ArH),5.81(t,J=8Hz,1H,C=CH),4.30(brs,2H,CH2OH),3.90(s,3H,CO2CH3),3.73(s,3H,OCH3),2.61(t,J=8Hz,2H,ArCH2),2.28(q,J=8Hz,2H,ArCH2CH2),2.04(brs,9H,adamantyl),and 1.73(brs,6H,adamantyl);13C NMR(75MHz,CDCl3)δ166.00(C=O),158.66,140.03,138.74,136.17,133.31,130.20,129.64,129.07,128.40,128.35,126.25,120.28,111.95,67.89(CH2OH),54.89(OCH3),52.17(CO2CH3),40.65,37.13,36.65,35.52,30.31,29.70,and 29.08;IR(film)3400(br,OH),2905,2850,1725(C=O),1450,1440,1410,1285,1270,1245,and 1110cm-1;MS(DCI)m/e 461(MH+),460(M+),459(M-H)+,and 443(MH+-H2O).
對(duì)于(Z)-2-(3-乙氧羰基苯基)-5-[3-(1-金剛烷基)-4-甲氧苯基]-2-戊烯醇(8j),將約1∶1的7j(3∶1,Z∶E)和1-(叔丁基二甲基甲硅烷氧基)-2-苯基-5-[3-(1-金剛烷基)-4-叔丁基二甲基甲硅烷氧苯基]-2-戊烯(3∶1,Z∶E)(1.6g)混合物溶于30ml3∶1∶1乙酸/THF/H2O,并攪拌48h。真空除去溶劑。通過硅膠柱層析純化殘余物(用二氯甲烷至5%甲醇/二氯甲烷洗脫),得到0.490g純(Z)-2-(3-乙氧羰基苯基)-5-[3-(1-金剛烷基)-4-叔丁基二甲基甲硅烷氧苯基]-2-戊烯醇(按起始混合物中800mg 7j計(jì)74%)1H NMR(300MHz,CDCl3)δ7.96(dt,J=8,1Hz,1H,2-ArH),7.89(t,J=1Hz,1H,2-ArH),7.38(t,J=8Hz,1H,2-ArH),7.22(m,1H,2-ArH),6.91(d,J=2Hz,1H,5-ArH),6.77(dd,J=2,8Hz,1H,5-ArH),6.63(d,J=8Hz,1H,5-ArH),5.82(t,J=8Hz,1H,C=CH),4.23-4.40(m,4H,CH2OH and CO2CH2CH3),2.59(t,J=8Hz,2H,ArCH2),2.26(q,J=8Hz,2H,ArCH2CH2),2.08(s,9H,adamantyl),1.76(s,6H,adamantyl),1.39(t,J=8Hz,3H,CO2CH2CH3),1.01(s,9H,SiC(CH3)3),and 0.31(s,6H,Si(CH3)2).
按合成5x時(shí)所述方法,首先用氟化四丁銨處理,然后用硫酸二甲酯烷基化,從而使(Z)-2-(3-乙氧羰基苯基)-5-[3-(1-金剛烷基)-4-叔丁基二甲基甲硅烷氧苯基]-2-戊烯醇(490mg)分兩步轉(zhuǎn)化為8j。經(jīng)硅膠柱層析純化8j(用30%乙酸乙酯/己烷洗脫)后得到0.150g純8j(兩步為37%)1H NMR(300MHz,CDCl3)δ7.96(dt,J=1,8Hz,1H,2-ArH),7.89(t,J=1Hz,1H,2-ArH),7.39(t,J=8Hz,1H,2-ArH),7.28(m,1H,2-ArH),6.92(d,J=2Hz,1H,5-ArH),6.89(dd,J=2,8Hz,1H,5-ArH),6.76(d,J=8Hz,1H,5-ArH),5.83(t,J=8Hz,1H,C=CH),4.33-4.42(m,4H,CH2OH and CO2CH2CH3),3.80(s,3H,OCH3),2.61(t,J=8Hz,2H,ArCH2),2.29(q,J=8Hz,2H,ArCH2CH2),2.06(s,9H,adamantyl),1.76(s,6H,adamantyl),and 1.40(t,J=8Hz,3H,CO2CH2CH3).
對(duì)于(Z)-2-(3-甲氧羰基苯基)-3-(3,4-雙戊氧苯基)-2-丙烯醇(8k)量度=1.08mmol,產(chǎn)率=96%;
1H NMR(300MHz,CDCl3)δ7.94-7.97(m,2H,2-ArH),7.36-7.44(m,2H,2-ArH),6.64(d,J=8Hz,1H,3-ArH),6.63(brs,1H,C=CH),6.57(dd,J=2,8Hz,1H,3-ArH),6.39(d,J=2Hz,1H,3-ArH),4.35(dd,J=1.5,6Hz,2H,CH2OH),3.90(t,J=6.5Hz,2H,ArOCH2),3.87(s,3H,CO2CH3),3.48(t,J=6.5Hz,2H,ArOCH2),1.70-1.79(m,2H,ArOCH2CH2),1.63(t,J=6Hz,1H,OH),1.55-1.65(m,2H,ArOCH2CH2),1.22-1.44(m,8H,4×CH2),and 0.88(t,J=7Hz,6H,2×CH3);13C NMR(75MHz,CDCl3)δ166.80(C=O),148.33,148.20,139.61,138.28,134.00,130.82,129.85,128.92,128.67,128.57,127.59,122.57,114.04,112.93,68.99,68.74,68.58,52.17(CO2CH3),28.88,28.66,28.15,28.01,22.44,22.36,and 14.02;IR(film)3430(br,OH),2955,2935,2870,1725(C=O),1510,1470,1440,1265,1235,1205,1170,1140,1110,1090,1020,and 760cm-1;MS(DCI)m/e 441(MH+),423(M+-OH).
實(shí)施例8合成化合物9的一般方法向醇8的二氯甲烷溶液(0.1M)中一次性加入二氧化錳(5∶1的MnO2/醇)。將反應(yīng)混合物在塞好的燒瓶中于室溫?cái)嚢?-18h。根據(jù)需要繼續(xù)加入MnO2以使反應(yīng)完全。通過1英寸硅藻土塞過濾棕色淤漿,并用二氯甲烷洗滌收集的固體。真空濃縮濾液,所得醛產(chǎn)物不經(jīng)純化直接使用。
對(duì)于(Z)-2-(3-乙氧羰基苯基)-3-苯基-2-丙烯醛(9a)量度=0.96mmol,產(chǎn)率=85%;
1H NMR(300MHz,CDCl3)δ9.80(s,1H,CHO),8.07-8.11(dt,J=2,8Hz,1H,2-ArH),7.88(t,J=2Hz,1H,2-ArH),7.15-7.50(m,8H,ArH),4.35(q,J=7Hz,2H,CO2CH2),and 1.35(t,J=7Hz,3H,CO2CH2CH3).
對(duì)于(Z)-2-(3-乙氧羰基苯基)-3-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-丙烯醛(9b)量度=2.13mmol,產(chǎn)率=90%;
1H NMR(300MHz,CDCl3)δ9.78(s,1H,CHO),8.09(dt,J=2,8Hz,1H,2-ArH),7.92(t,J=2Hz,1H,2-ArH),7.55(t,J=8Hz,1H,2-ArH),7.38-7.43(m,2H,ArH and C=CH),7.20(d,J=8Hz,1H,3-ArH),7.12(d,J=2Hz,1H,3-ArH),6.97(dd,J=2,8Hz,1H,3-ArH),4.36(q,J=7Hz,2H,CO2CH2),1.60(brs,4H,CH2CH2),1.35(t,J=7Hz,3H,CO2CH2CH3),1.22(s,6H,2×CH3),and 0.98(s,6H,2×CH3).
對(duì)于(Z)-2-(3-乙氧羰基苯基)-3-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2-丙烯醛(9c)量度=0.89mmol,產(chǎn)率=88%;
1H NMR(300MHz,CDCl3)δ9.80(s,1H,CHO),8.08(dt,J=2,8Hz,1H,2-ArH),7.93(t,J=2Hz,1H,2-ArH),7.74(s,1H,ArH or C=CH),7.66(s,2H,ArH),7.57(s,1H,ArH or C=CH),7.36-7.49(m,3H,ArH),6.92(dd,J=2,9Hz,1H,ArH),4.33(q,J=7Hz,2H,CO2CH2),1.73(s,4H,CH2CH2),and 1.31-1.41(m,15H,4×CH3and OCH2CH3);13C NMR(75MHz,CDCl3)δ193.57(CH=O),166.32(C=O),151.49,146.93,145.45,140.18,134.18,133.89,132.32,132.11,131.33,131.15,130.79,130.55,129.51,128.86,127.35,125.90,125.33,124.88,61.09(CO2CH2),34.88(CH2CH2),34.78,34.60,32.43 and 32.39(4×CH3),and 14.28(CO2CH2CH3);IR(KBr)2960,2930,1720(ester C=O),1685(CH=O),1470,1365,1270,1210,1190,1110,and 1090cm-1;MS(DCI)m/e 441(MH+).
對(duì)于(Z)-2-(3-乙氧羰基苯基)-3-(4-癸氧苯基)-2-丙烯醛(9d)量度=1.70mmol,產(chǎn)率=80%;
1H NMR(300MHz,CDCl3)δ9.72(s,1H,CHO),8.08(dt,J=2,8Hz,1H,2-ArH),7.91(t,J=2Hz,1H,2-ArH),7.51(t,J=8Hz,1H,2-ArH),7.39(dt,J=2,8Hz,1H,2-ArH),7.37(s,1H,C=CH),7.12(d,J=8Hz,2H,3-ArH),6.72(d,J=8Hz,2H,3-ArH),3.92(t,J=7Hz,2H,ArOCH2),3.90(s,3H,CO2CH3),1.75(quintet,J=7Hz,2H,ArOCH2CH2),1.20-1.46(m,14H,7×CH2),and 0.87(t,J=7Hz,3H,CH3).
對(duì)于(Z)-2-(3-乙氧羰基苯基)-3-(3,4-雙癸氧苯基)-2-丙烯醛(9e)量度=0.46mmol,產(chǎn)率=93%;
1H NMR(300MHz,CDCl3)δ9.70(s,1H,CHO),8.05(dt,J=2,8Hz,1H,2-ArH),8.03(t,J=2Hz,1H,2-ArH),7.50(t,J=8Hz,1H,2-ArH),7.39(dt,J=2,8Hz,1H,2-ArH),7.33(s,1H,C=CH),6.87(dd,J=2,8Hz,1H,3-ArH),6.73(d,J=8Hz,1H,3-ArH),6.55(d,J=2Hz,1H,3-ArH),4.33(q,J=6Hz,2H,CO2CH2),3.95(t,J=7Hz,2H,ArC4OCH2),3.45(t,J=7Hz,2H,ArC3OCH2),1.77(quint,J=7Hz,2H,ArC4OCH2CH2),1.55-1.60(m,2H,ArC3OCH2CH2),1.35(t,J=6Hz,3H,CO2CH2CH3),1.19-1.40(m,28H,14×CH2),and 0.83-0.88(m,6H,2×CH3);13C NMR(75MHz,CDCl3)δ193.45(CH=O),166.14(C=O),151.46,151.17,148.36,139.63,134.55,134.15,131.28,130.79,129.24,129.00,126.27,126.01,114.42,112.32,68.91,68.57,61.09(CO2CH2),31.91,29.57,29.33,28.98,28.85,25.91,25.78,22.68,14.30,and 14.12;IR(KBr)2960,2920,2875,2850,1715(ester C=O),1675(CH=O),1665,1615,1595,1570,1515,1475,1430,1285,1270,1245,1210,1145,and 1120cm-1;MS(FAB)m/e 593(MH+).
對(duì)于(Z)-2-(3-乙氧羰基苯基)-5-苯基-2-戊烯醛(9f)量度=0.76mmol,產(chǎn)率=88%;
1H NMR(300MHz,CDCl3)δ9.62(s,1H,CHO),8.04(dt,J=2,8Hz,1H,2-ArH),7.80(t,J=2Hz,1H,2-ArH),7.45(t,J=8Hz,1H,2-ArH),7.11-7.31(m,6H,1×2-ArH and 5×5-ArH),6.79(t,J=7.5Hz,1H,C=CH),4.40(q,J=7Hz,2H,CO2CH2),2.85(t,J=7.5Hz,2H,ArCH2),2.68(q,J=7.5Hz,2H,ArCH2CH2),and 1.40(t,J=7Hz,3H,CO2CH2CH3);MS(DCI)m/e 309(MH+).
對(duì)于(Z)-2-(3-甲氧羰基苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-戊烯醛(9g)量度=0.62mmol,產(chǎn)率=100%;
1H NMR(300MHz,CDCl3)δ9.62(s,1H,CHO),8.01(d,J=8Hz,1H,2-ArH),7.82(s,1H,2-ArH),7.41(t,J=8Hz,1H,2-ArH),7.21(d,J=8Hz,1H,2-ArH),7.09(d,J=7Hz,1H,5-ArH),7.03(s,1H,5-ArH),6.88(d,J=8Hz,1H,5-ArH),6.82(t,J=7Hz,1H,C=CH),4.38(q,J=7Hz,2H,CO2CH2),2.78(m,2H,ArCH2),2.64(q,J=7Hz,2H,ArCH2CH2),1.66(s,4H,CH2CH2),1.39(t,J=7Hz,3H,CO2CH2CH3),1.26(s,6H,2×CH3),and 1.23(s,6H,2×CH3).
對(duì)于(2Z),(4E)-2-(3-乙氧羰基苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-己二烯醛(9h)量度=0.54mmol,產(chǎn)率=89%;
1H NMR(300MHz,CDCl3)δ9.72(s,1H,CHO),8.02(dt,J=2,8Hz,1H,2-ArH),7.94(d,J=2Hz,1H,2-ArH),7.79(brd,J=12Hz,1H,C=CH),7.48-7.59(m,2H,2-ArH),7.35(d,J=2Hz,1H,5-ArH),7.27(d,J=8Hz,1H,5-ArH),7.17(dd,J=2,8Hz,1H,5-ArH),6.74(brd,J=12Hz,1H,C=CH),4.36(q,J=7Hz,2H,CO2CH2),2.43(d,J=1.5Hz,3H,C=CCH3),1.66(brs,4H,CH2CH2),1.36(t,J=7Hz,3H,CO2CH2CH3),1.23(s,6H,2×CH3),and 1.21(s,6H,2×CH3).
對(duì)于(Z)-2-(3-甲氧羰基苯基)-5-[4-(1-金剛烷基)-3-甲氧苯基]-2-戊烯醛(9i)量度=0.93mmol,產(chǎn)率=88%;
1H NMR(300MHz,CDCl3)δ9.59(s,1H,CHO),7.99(dt,J=2,8Hz,1H,2-ArH),7.79(t,J=2Hz,1H,2-ArH),7.41(t,J=8Hz,1H,2-ArH),7.10(dt,J=2,8Hz,1H,2-ArH),7.08(d,J=8Hz,1H,3-ArH),6.79(t,J=7Hz,1H,C=CH),6.65(dd,J=2,8Hz,1H,3-ArH),6.56(d,J=2Hz,1H,3-ArH),3.89(s,3H,CO2CH3),3.74(s,3H,OCH3),2.78(t,J=7Hz,2H,ArCH2),2.64(q,J=7Hz,2H,ArCH2CH2),2.08(brs,9H,adamantyl),and 1.74(brs,6H,adamantyl);13C NMR(75MHz,CDCl3)δ193.08(CH=O),166.76(ester C=O),158.88,155.58,143.64,138.64,136.75,133.98,132.77,130.49,130.22,129.16,128.34,126.55,120.23,111.82,54.91(OCH3),52.16(CO2CH3),40.64,37.50,37.11,36.72,34.40,31.38,and 29.09.
對(duì)于(Z)-2-(3-乙氧羰基苯基)-5-[3-(1-金剛烷基)-4-甲氧苯基]-2-戊烯醛(9j)量度=0.32mmol,產(chǎn)率=93%;
1H NMR(300MHz,CDCl3)δ9.61(s,1H,CHO),8.02(dt,J=8,1Hz,1H,2-ArH),7.81(t,J=1Hz,1H,2-ArH),7.44(t,J=8Hz,1H,2-ArH),7.19(dt,J=8,1Hz,1H,2-ArH),6.89-6.95(m,2H,5-ArH and C=CH),6.75-6.83(m,2H,5-ArH),4.37(q,J=7Hz,2H,CO2CH2),3.80(s,3H,OCH3),2.76(t,J=7Hz,2H,ArCH2),2.64(q,J=7Hz,2H,ArCH2CH2),2.04(s,9H,adamantyl),1.76(s,6H,adamantyl),and 1.39(t,J=7Hz,3H,CO2CH2CH3).
對(duì)于(Z)-2-(3-甲氧羰基苯基)-3-(3,4-雙戊氧苯基)-2-丙烯醛(9k)量度=0.99mmol,產(chǎn)率=96%;
1H NMR(300MHz,CDCl3)δ9.72(s,1H,CHO),8.07(dt,J=2,8Hz,1H,2-ArH),7.93(t,J=2Hz,1H,2-ArH),7.53(t,J=8Hz,1H,2-ArH),7.42(dt,J=2,8Hz,1H,2-ArH),7.35(s,1H,C=CH),6.90(dd,J=2,8Hz,1H,3-ArH),6.75(d,J=8Hz,1H,3-ArH),6.39(d,J=2Hz,1H,3-ArH),3.98(t,J=6.5Hz,2H,3-ArOCH2),3.89(s,3H,CO2CH3),3.47(t,J=6.5Hz,2H,3-ArOCH2),1.75-1.86(m,2H,3-ArOCH2CH2),1.56-1.66(m,2H,3-ArOCH2CH2),1.25-1.49(m,8H),and 1.86-1.96(m,6H,2×CH3).
實(shí)施例9合成化合物10的一般方法將18-冠-6(5當(dāng)量)和雙(2,2,2-三氟乙基)(甲氧羰基甲基)膦酸酯(1.1當(dāng)量)的無水四氫呋喃溶液在氬氣下冷卻至-78℃。加入雙三甲基甲硅烷基氨化鉀(0.5M于苯,1.1當(dāng)量),接著加入醛9(1當(dāng)量)的四氫呋喃溶液(0.05M終濃度)。將反應(yīng)混合物溫?zé)嶂潦覝?,然后倒入裝有乙醚和飽和氯化銨溶液的分液漏斗中。用飽和氯化鈉溶液進(jìn)一步洗滌醚層,于無水硫酸鎂上干燥,并濃縮。經(jīng)柱層析純化(30∶1-40∶1硅膠/粗產(chǎn)物;用5%乙酸乙酯/己烷洗脫)后得到目的產(chǎn)物。
對(duì)于(2Z),(4Z)-4-(3-乙氧羰基苯基)-5-苯基-2,4-戊二烯酸甲酯(10a)量度=0.82mmol,產(chǎn)率=93%;
1H NMR(300MHz,CDCl3)δ7.94(dt,J=2,8Hz,1H,4-ArH),7.86(t,J=2Hz,1H,4-ArH),7.30-7.37(m,2H,4-ArH),7.08-7.11(m,3H,5-ArH),6.91-6.94(m,2H,5-ArH),6.86(s,1H,C=CH),6.67(d,J=12Hz,1H,CH=CHCO2),5.87(d,J=12Hz,1H,CH=CHCO2),4.32(q,J=7Hz,2H,CO2CH2),3.31(s,3H,CO2CH3),and 1.34(t,J=7Hz,3H,CO2CH2CH3);13C NMR(75MHz,CDCl3)δ166.72(C=O),166.35(C=O),142.77,138.38,136.95,135.77,135.09,134.24,130.82,130.47,129.58,128.72,128.52,128.10,127.70,120.58,61.01(CO2CH2),51.27(CO2CH3)and 14.28(CO2CH2CH3);IR(film)2980,2950,1720(C=O),1435,1265,1195,1175,1110,1085,1020,760,and 700cm-1;MS(DCI)m/e 336(M+).
對(duì)于(2Z),(4Z)-4-(3-乙氧羰基苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-戊二烯酸甲酯(10b)量度=1.05mmol,產(chǎn)率=83%;
UVmax(CH3OH)308nm(ε=20,100),228nm(ε=22,700);1H NMR(300MHz,CDCl3)δ7.94-7.98(m,1H,4-ArH),7.90(t,J=2Hz,1H,4-ArH),7.37-7.43(m,2H,4-ArH),7.06(d,J=8Hz,1H,5-ArH),6.80(s,2H,5-ArH and C=CH),6.73(dd,J=2,8Hz,1H,5-ArH),6.64(d,J=12Hz,1H,CH=CHCO2),5.80(d,J=12Hz,1H,CH=CHCO2),4.32(q,J=7Hz,2H,CO2CH2),3.25(s,3H,CO2CH3),1.50-1.58(m,4H,CH2CH2),1.33(t,J=7Hz,3H,CO2CH2CH3),1.17(s,6H,2×CH3),and 0.92(s,6H,2×CH3);13C NMR(75MHz,CDCl3)δ166.90(C=O),166.38(C=O),145.04,144.45,142.72,138.85,136.23,136.03,134.26,132.64,130.88,130.70,128.67,128.60,127.81,127.30,126.39,119.65,60.95(CO2CH2),51.24(OCH3),34.88,34.13,33.89,31.61,31.38,and 14.31(CO2CH2CH3);IR(film)2960,2930,2860,1720(C=O),1460,1440,1280,1265,1195,1170,1110,1085,and 755cm-1;MS(DCI)m/e 447(MH+),415(M+-OCH3).
對(duì)于(2Z),(4Z)-4-(3-乙氧羰基苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2,4-戊二烯酸甲酯(10c)量度=0.76mmol,產(chǎn)率=94%;
1H NMR(300MHz,CDCl3)δ7.96(dt,J=2,8Hz,1H,4-ArH),7.91(t,J=2Hz,1H,4-ArH),7.58(d,J=12Hz,2H,ArH),7.47(s,1H,ArH),7.29-7.40(m,3H,ArH),7.01(brs,1H,C=CH),6.75(dd,J=2,9Hz,1H,ArH),6.72(dd,J=1,12Hz,1H,CH=CHCO2),5.88(d,J=12Hz,1H,CH=CHCO2),4.32(q,J=7Hz,2H,CO2CH2),3.30(s,3H,CO2CH3),1.72(s,4H,CH2CH2),and 1.29-1.36(m,15H,4×CH3)and CO2CH2CH3);13C NMR(75MHz,CDCl3)δ166.89(C=O),166.41(C=O),145.12,144.69,142.97,138.61,136.51,135.74,134.51,132.58,131.54,131.10,130.82,130.50,129.22,128.76,128.49,126.62,125.82,125.21,124.62,120.37,61.01(CO2CH3),51.28(CO2CH2),35.00,34.60,34.52,32.44,and 14.24(CO2CH2CH3);IR(film)2960,2860,1720(C=O),1365,1270,1195,1175,and 1110cm-1;MS(DCI)m/e 497(MH+),465(MH+-CH3OH).
對(duì)于(2Z),(4Z)-4-(3-乙氧羰基苯基)-5-(4-癸氧苯基)-2,4-戊二烯酸甲酯(10d)量度=1.37mmol,產(chǎn)率=98%;
1H NMR(300MHz,CDCl3)δ7.95(dt,J=2,8Hz,1H,4-ArH),7.88(t,J=2Hz,1H,4-ArH),7.34-7.41(m,2H,4-ArH),6.82(d,J=8Hz,2H,5-ArH),6.81(s,1H,C=CH),6.63(d,J=12Hz,1H,CH=CHCO2),6.61(d,J=8Hz,2H,5-ArH),5.79(d,J=12Hz,1H,CH=CHCO2),3.88(s,3H,CO2CH3),3.85(t,J=7Hz,2H,ArOCH2),3.26(s,3H,CO2CH3),1.70(quintet,J=7Hz,2H,ArOCH2CH2),1.17-1.42(m,14H,7×CH2),and 0.85(t,J=7Hz,3H,CH3);13C NMR(75MHz,CDCl3)δ166.90(C=O),158.86,142.94,138.88,135.64,134.91,134.48,131.09,130.58,128.66,128.00,119.42,114.11,67.91(ArOCH2),52.17(CO2CH3),51.24(CO2CH3),31.88,29.54,29.36,29.31,29.16,25.98,22.68,and 14.12;IR(film)2925,2855,1725,(C=O),1600,1510,1470,1435,1280,1270,1250,1195,1175,1110,1085,1070,1000,825,755,and 710cm-1;MS(DCI)m/e 479(MH+),447(M+-OCH3).
對(duì)于(2Z),(4Z)-4-(3-乙氧羰基苯基)-5-(3,4-雙癸氧苯基)-2,4-戊二烯酸甲酯(10e)量度=0.41mmol,產(chǎn)率=86%;
1H NMR(300MHz,CDCl3)δ7.90-7.96(m,2H,4-ArH),7.38-7.48(m,2H,4-ArH),6.79(s,1H,C=CH),6.56-6.65(m,3H,2×5-ArH and CH=CHCO2),6.32(d,J=2Hz,1H,5-ArH),4.78(d,J=12Hz,1H,CH=CHCO2),4.33(q,J=7Hz,2H,CO2CH2),3.90(t,J=7Hz,2H,ArC4OCH2),3.45(t,J=7Hz,2H,ArC3OCH2),3.25(s,3H,CO2CH3),1.74(quint,J=7Hz,2H,ArC4OCH2CH2),1.54-1.60(m,2H,ArC3OCH2CH2),1.35(t,J=7Hz,3H,CO2CH2CH3),1.19-1.40(m,28H,14×CH2),and 0.83-0.88(m,6H,2×CH3);13C NMR(75MHz,CDCl3)δ166.93(C=O),166.27(C=O),149.06,148.17,142.78,135.03,134.97,134.45,130.93,130.75,128.62,128.54,128.37,123.68,119.28,114.05,112.67;68.93,68.57,61.03(CO2CH2),51.22(CO2CH3),31.91,29.58,29.37,29.34,29.13,28.98,25.95,25.83,22.68,14.30,and 14.12;IR(film)2925,2855,1720(C=O),1510,1470,1265,1200,1170,and 1140cm-1;MS(DCI)m/e 649(MH+).
對(duì)于(2Z),(4Z)-4-(3-乙氧羰基苯基)-7-苯基-2,4-庚二烯酸甲酯(10f)量度=0.65mmol,產(chǎn)率=77%;
UVmax(CH3OH)262nm(ε=10,600);1H NMR(300MHz,CDCl3)δ7.89(dt,J=2,8Hz,1H,4-ArH),7.70(t,J=2Hz,1H,4-ArH),7.39(t,J=8Hz,1H,4-ArH),7.04-7.22(m,6H,1×4-ArH and 5×7-ArH),6.60(d,J=12Hz,1H,CH=CHCO2),6.06(t,J=7.5Hz,1H,C=CH),5.74(d,J=12Hz,1H,CH=CHCO2),4.35(q,J=7Hz,2H,CO2CH2),3.14(s,3H,CO2CH3),2.68(t,J=7.5Hz,2H,ArCH2),2.32(q,J=7.5Hz,2H,ArCH2CH2),and 1.38(t,J=7Hz,3H,CO2CH2CH3);13C NMR(75MHz,CDCl3)δ168.68(C=O),167.89(C=O),142.98,142.46,139.60,139.43,139.33,135.01,131.44,131.26,129.47,129.35,129.30,129.10,127.02,120.01,62.21(CO2CH2),51.61(CO2CH3),36.37,32.30,and 14.63(CO2CH2CH3);IR(film)3060,3025,2980,2950,2855,1720(C=O),1455,1435,1370,1270,1195,1170,1110,1085,1020,760,and 700cm-1;MS(DCI)m/e 365(MH+),333(M+-OCH3).
對(duì)于(2Z),(4Z)-4-(3-甲氧羰基苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸甲酯(10g)量度=0.62mmol,產(chǎn)率=85%;
1H NMR(300MHz,CDCl3)δ7.92(d,J=8Hz,1H,4-ArH),7.85(s,1H,4-ArH),7.36(t,J=8Hz,1H,4-ArH),7.15-7.24(m,2H,4-ArH and 7-ArH),7.00(d,J=2Hz,1H,7-ArH),6.84(dd,J=2,8Hz,1H,7-ArH),6.57(d,J=12Hz,1H,CH=CHCO2),6.07(t,J=7Hz,1H,C=CH),5.73(d,J=12Hz,1H,CH=CHCO2),4.36(q,J=7Hz,2H,CO2CH2),3.21(s,3H,OCH3),2.63(t,J=8Hz,2H,ArCH2),2.35(q,J=8Hz,2H,ArCH2CH2),1.64(s,4H,CH2CH2),1.38(t,J=7Hz,3H,CO2CH2CH3),1.24(s,6H,2×CH3),and 1.22(s,6H,2×CH3);13C NMR(75MHz,CDCl3)δ166.80(C=O),166.47(C=O),144.71,142.48,142.26,138.53,138.20,137.98,137.28,133.51,130.29,130.12,128.21,128.06,126.46,126.39,125.64,119.07,61.01(CO2CH2),51.09(OCH3),35.22,35.15,35.09,34.15,33.94,31.89,31.84,31.13,and 14.35(CO2CH2CH3);IR(film)2960,2925,1720(C=O),1270,and 1170cm-1;MS(DCI)m/e 475(MH+),474(M+);Exact mass spectrum(FAB)Calcd for C31H38O4Na:497.2668(MNa+).Found:497.2652.
對(duì)于(2Z),(4Z)-4-(3-乙氧羰基苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4,6-辛三烯酸甲酯(10h)量度=0.47mmol,產(chǎn)率=74%;
UVmax(CH3OH)348nm(ε=14,300);1H NMR(300MHz,CDCl3)δ7.95(dt,J=2,8Hz,1H,4-ArH),7.91(d,J=2Hz,1H,4-ArH),7.41-7.51(m,2H,4-ArH),7.04-7.22(m,4H,3×7-ArH and C=CH),6.81(d,J=12Hz,1H,CH=CHCO2),6.41(brd,J=12Hz,1H,C=CH),5.82(d,J=12Hz,1H,CH=CHCO2),4.35(q,J=7Hz,2H,CO2CH2),3.15(s,3H,CO2CH3),2.25(d,J=1.5Hz,3H,C=CCH3),1.63(s,4H,CH2CH2),1.35(t,J=7Hz,3H,CO2CH2CH3),1.21(s,6H,2×CH3),and 1.16(s,6H,2×CH3);13C NMR(75MHz,CDCl3)δ168.50(C=O),167.90(C=O),145.89,145.69,143.19,140.96,140.17,138.62,135.27,134.69,132.02,131.50,129.44,129.26,127.62,124.73,124.09,123.55,120.03,62.29(CO2CH2),51.64(OCH3),36.18,36.09,35.18,35.04,32.21,32.08,16.20(C=CCH3),and 14.62(CO2CH2CH3);IR(film)2960,2930,2860,1720(C=O),1460,1440,1365,1265,1205,1170,1110,1085,and 760cm-1;MS(DCI)m/e 487(MH+),455(M+-OCH3).
對(duì)于(2Z),(4Z)-4-(3-甲氧羰基苯基)-7-[4-(1-金剛烷基)-3-甲氧苯基]-2,4-庚二烯酸甲酯(10i)量度=0.81mmol,產(chǎn)率=69%;
1H NMR(300MHz,CDCl3)δ7.91(dt,J=2,8Hz,1H,4-ArH),7.84(t,J=2Hz,1H,4-ArH),7.36(t,J=8Hz,1H,4-ArH),7.21(dt,J=2,8Hz,1H,4-ArH),7.05(d,J=8Hz,1H,7-ArH),6.62(dd,J=2,8Hz,1H,7-ArH),6.54-6.58(m,2H,7-ArH and CH=CHCO2),6.05(t,J=8Hz,1H,C=CH),5.72(d,J=12Hz,1H,CH=CHCO2),3.89(s,3H,ArCO2CH3),3.73(s,3H,OCH3),3.21(s,3H,CO2CH3),2.63(t,J=8Hz,2H,ArCH2),2.36(q,J=8Hz,2H,ArCH2CH2),2.04(brs,9H,adamantyl),and 1.73(brs,6H,adamantyl);13C NMR(75MHz,CDCl3)δ166.40(C=O),166.30(C=O),142.20,139.71,138.19,137.30,136.27,133.62,130.16,129.96,128.23,128.10,126.31,120.22,119.17,111.94,54.89(OCH3),52.12(ArCO2CH3),51.06(CO2CH3),40.66,37.13,36.66,35.12,30.94,and 29.10.
對(duì)于(2Z),(4Z)-4-(3-乙氧羰基苯基)-7-[3-(1-金剛烷基)-4-甲氧苯基]-2,4-庚二烯酸甲酯(10j)量度=0.29mmol,產(chǎn)率=76%;
1H NMR(300MHz,CDCl3)δ7.92(dt,J=2,8Hz,1H,4-ArH),7.83(t,J=2Hz,1H,4-ArH),7.37(t,J=8Hz,1H,4-ArH),7.25(dt,J=2,8Hz,1H,4-ArH),6.91(d,J=8Hz,1H,7-ArH),6.87(dd,J=2,8Hz,1H,7-ArH),6.73(d,J=8Hz,1H,7-ArH),6.57(d,J=13Hz,1H,CH=CHCO2),6.06(t,J=8Hz,1H,C=CH),5.73(d,J=12Hz,1H,CH=CHCO2),4.36(q,J=7Hz,2H,CO2CH2),3.77(s,3H,OCH3),3.20(s,3H,CO2CH3),2.62(t,J=8Hz,2H,ArCH2),2.34(q,J=8Hz,2H,ArCH2CH2),2.03(s,9H,adamantyl),1.74(s,6H,adamantyl),and 1.38(t,J=7Hz,3H,CO2CH2CH3);13C NMR(75MHz,CDCl3)δ166.83(C=O),166.50(C=O),157.13,142.28,138.67,138.33,138.22,137.28,133.55,132.72,130.28,130.12,128.18,128.07,126.72,126.23,119.01,111.59,61.02(CO2CH2),55.06,51.09,40.56,37.13,36.86,35.01,31.44,29.10,and 14.34(CO2CH2CH3);IR(film)2905,2850,1720(C=O),1495,1270,and 1235cm-1;MS(DCI)m/e 529(MH+),135(C10H15+).Anal.Calcd for C34H40O5:C,77.24;H,7.63.Found:C,77.55;H,7.56.
對(duì)于(2Z),(4Z)-4-(3-甲氧羰基苯基)-5-(3,4-雙戊氧苯基)-2,4-戊二烯酸甲酯(10k)量度=0.63mmol,產(chǎn)率=85%;
1H NMR(300MHz,CDCl3)δ7.91-7.96(m,2H,4-ArH),7.36-7.45(m,2H,4-ArH),6.79(s,1H,C=CH),6.56-6.66(m,3H,2×5-ArH and CH=CHCO2),6.31(d,J=2Hz,1H,5-ArH),5.78(d,J=12Hz,1H,CH=CHCO2),3.89(t,J=6.5Hz,2H,ArOCH2),3.87(s,3H,CO2CH3),3.44(t,J=6.5Hz,2H,ArOCH2),3.25(s,3H,CO2CH3),1.70-1.80(m,2H,ArOCH2CH2),1.54-1.60(m,2H,ArOCH2CH2),1.25-1.43(m,8Hz,4×CH2),and 0.86-0.94(m,6H,2×CH3);13C NMR(75MHz,CDCl3)δ166.92(C=O),166.75(C=O),149.06,148.16,142.76,139.05,136.06,134.93,134.58,130.81,130.59,128.67,128.59,128.34,123.71,119.30,114.00,112.65,68.91(ArOCH2),68.52(ArOCH2),52.16(CO2CH3),51.22(CO2CH3),28.81,28.64,28.13,27.99,22.43,22.35,and 14.02;IR(film)2955,2870,1725(C=O),1595,1510,1470,1435,1265,1200,1170,1140,1110,and 1000cm-1;MS(DCI)m/e 495(MH+),463(M+-OCH3).
實(shí)施例10a合成11a-j化合物的一般方法將酯10的甲醇/四氫呋喃/2N氫氧化鈉溶液混合物(1∶1∶1,0.1M)回流加熱1-4h。然后冷卻至室溫,加10%鹽酸溶液至溶液pH1。所得混濁混合物用二氯甲烷(2-4次)萃取,有機(jī)相用鹽水洗滌,于無水硫酸鎂上干燥,過濾,并濃縮。殘余物自戊烷(3批)中蒸發(fā),然后真空干燥。
對(duì)于(2Z),(4Z)-4-(3-羧基苯基)-5-苯基-2,4-戊二烯酸(11a)量度=2.05mmol,產(chǎn)率=99%;
UVmax(CH3OH)269nm(ε=14,700),222nm(ε=23,500);1H NMR(300MHz,CDCl3)δ7.90-7.95(m,1H,4-ArH),7.86(t,J=2Hz,1H,4-ArH),7.37-7.41(m,2H,4-ArH),7.06-7.13(m,3H,5-ArH),6.95-6.98(m,2H,5-ArH),6.90(s,1H,C=CH),6.71(d,J=12Hz,1H,CH=CHCO2),and 5.92(d,J=12Hz,1H,CH=CHCO2);13C NMR(75MHz,CD3OD)δ170.12(C=O),169.54(C=O),143.47,140.11,138.83,137.47,135.51,135.15,132.14,130.66,129.91,129.63,129.09,128.67,and 122.57;IR(film)2200-3400(br,CO2H),1695(C=O),1625,1600,1580,1435,1305,1275,1250,1230,950,910,750,and 690cm-1;MS(DCI)m/e 295(MH+).Anal.Calcd for C18H14O4:C,73.46;H,4.79.Found:C,73.40;H,4.78.
對(duì)于(2Z),(4Z)-4-(3-羧基苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-戊二烯酸(11b)量度=1.35mmol,產(chǎn)率=98%;
UVmax(CH3OH)308nm(ε=15,200),228nm(ε=21,100);1H NMR(300MHz,CD3OD)δ7.91-7.96(m,1H,4-ArH),7.89(t,J=2Hz,1H,4-ArH),7.42-7.46(m,2H,4-ArH),7.13(d,J=8Hz,1H,5-ArH),6.82 and 6.85(2s,3H,2×5-ArH and C=CH),6.68(d,J=12Hz,1H,CH=CHCO2),5.86(d,J=12Hz,1H,CH=CHCO2),1.52-1.65(m,4H,CH2CH2),1.19(s,6H,2×CH3),and 0.89(s,6H,2×CH3);13C NMR(75MHz,CD3OD)δ170.29(C=O),169.63(C=O),145.89,145.32,143.52,140.66,137.87,136.09,135.52,134.32,132.35,129.81,128.71,127.46,121.76,36.04,35.05,34.82,32.03,and 31.87;IR(film)2500-3400(br,CO2H),1695(C=O),1615,1585,1440,1415,1365,1285,1225,and 910cm-1;MS(DCI)m/e 405(MH+),387(M+-OH),Anal.Calcd for C26H28O4·0.4H2O:C,75.85;H,7.05.Found:C,75.89;H,6.96.
對(duì)于(2Z),(4Z)-4-(3-羧基苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2,4-戊二烯酸(11c)量度=0.69mmol,產(chǎn)率=100%;
mp211-213℃;UVmax(CH3OH)332nm(ε=21,100),284nm(ε=21,700);1H NMR(300MHz,DMSO-d6)δ7.86(dt,J=2,8Hz,1H,4-ArH),7.74(s,1H,4-ArH),7.69(d,J=12Hz,2H,5-ArH),7.56(s,1H,ArH),7.34-7.44(m,3H,ArH),7.00(s,1H,C=CH),6.67-6.74(m,2H,ArH and CH=CHCO2),5.94(d,J=12Hz,1H,CH=CHCO2),1.67(s,4H,CH2CH2),and 1.29(brs,12H,4×CH3);13C NMR(75MHz,DMSO-d6)δ167.13(C=O),167.02(C=O),144.56,144.29,141.53,138.47,136.94,133.90,133.36,132.54,131.27,130.80,130.61,130.24,128.72,128.52,126.38,125.29,124.84,124.47,122.48,34.48,34.28,34.21,and 32.18;IR(KBr)3430(br,CO2H),3010,2960,2925,2865,1690(C=O),1615,1435,1290,1260,and 1225cm-1;MS(DCI)m/e 455(MH+)and 411(MH+-CO2H).Anal.Calcd for C30H30O4·0.67H2O:C,77.20;H,6.77.Found:C,77.21;H,6.58.
對(duì)于(2Z),(4Z)-4-(3-羧基苯基)-5-(4-癸氧苯基)-2,4-戊二烯酸(11d)量度=1.27mmol,產(chǎn)率=94%;
UVmax(CH3OH)314nm(ε=19,700),228nm(ε=23,000);1H NMR(300MHz,CDCl3)δ7.93-7.96(m,1H,4-ArH),7.88(t,J=2Hz,1H,4-ArH),7.38-7.41(m,2H,4-ArH),6.87(d,J=8Hz,2H,5-ArH),6.86(s,1H,C=CH),6.63-6.69(m,3H,CH=CHCO2and 2×5-ArH),5.85(d,J=12Hz,1H,CH=CHCO2),3.87(t,J=7Hz,2H,ArOCH2),1.70(quintet,J=7Hz,2H,ArOCH2CH2),1.21-1.42(m,14H,7×CH2),and 0.88(t,J=7Hz,3H,CH3);13C NMR(75MHz,CD3OD)δ169.25(C=O),160.30,143.78,140.51,136.75,135.62,132.16,129.82,129.71,121.47,115.08,68.92(ArOCH2),33.07,30.69,30.50,30.46,30.34,27.12,23.74,and 14.45;IR(KBr)2400-3500(br,CO2H),2950,2920,2850,1695(C=O),1605,1510,1465,1440,1420,1300,1255,1175,1025,935,915,890,830,and 750cm-1;MS(DCI)m/e 451(MH+).Anal.Calcd for C28H34O5:C,74.64;H,7.61.Found:C,74.50;H,7.56.
對(duì)于(2Z),(4Z)-4-(3-羧基苯基)-5-(3,4-雙癸氧苯基)-2,4-戊二烯酸(11e)量度=0.32mmol,產(chǎn)率=100%;
UVmax(CH2Cl2)342nm(ε=20,200);1H NMR(300MHz,CDCl3)δ8.01(s,1H,4-ArH),7.92-7.96(m,1H,4-ArH),7.40-7.45(m,2H,4-ArH),6.91(s,1H,C=CH),6.75(d,J=13Hz,1H,CH=CHCO2),6.64(d,J=8.5Hz,1H,5-ArH),6.58(dd,J=2,8.5Hz,1H,5-ArH),6.31(d,J=2Hz,1H,5-ArH),5.79(d,J=13Hz,1H,CH=CHCO2),3.89(t,J=7Hz,2H,ArC4OCH2),3.42(t,J=7Hz,2H,ArC3OCH2),1.73(quint,J=7Hz,2H,ArC4OCH2CH2),1.50-1.60(m,2H,ArC3OCH2CH2),1.21-1.38(m,28H,14×CH2),and 0.82-0.87(m,6H,2×CH3);13C NMR(75MHz,CDCl3)δ173.39(C=O),171.72(C=O),149.30,149.14,141.84,138.74,138.66,136.11,135.36,130.94,129.64,129.39,129.14,128.07,123.97,117.78,114.15,112.58,68.91,68.50,31.90,29.58,29.36,29.33,29.09,28.94,25.94,24.78,22.68,and 14.12;IR(KBr)2955,2925,2850,2665,1700(C=O),1585,1515,1435,1310,1270,1240,and 1140cm-1;MS(DCI)m/e 607(MH+),563(M-2×CO2H+2H)+.Anal.Calcd for C38H54O6:C,75.21;H,8.97.Found:C,75.22;H,8.97.
對(duì)于(2Z),(4Z)-4-(3-羧基苯基)-7-苯基-2,4-庚二烯酸(11f)量度=0.40mmol,產(chǎn)率=85%;
UVmax(CH3OH)262nm(ε=8,800);1H NMR(300MHz,CD3OD)δ7.90(dt,J=2,8Hz,1H,2-ArH),7.80(t,J=2Hz,1H,2-ArH),7.38(t,J=8Hz,1H,2-ArH),7.06-7.27(m,6H,1×2-ArH and 5×5-ArH),6.58(d,J=12Hz,1H,CH=CHCO2),6.04(t,J=7.5Hz,1H,C=CH),5.76(d,J=12Hz,1H,CH=CHCO2),2.68(t,J=7.5Hz,2H,ArCH2),and 2.33(q,J=7.5Hz,2H,ArCH2CH2);13C NMR(75MHz,CD3OD)δ170.10(C=O),143.14,142.60,139.70,139.13,137.78,134.94,131.66,129.49,129.43,129.34,129.14,126.96,121.16,36.41,and 32.43;IR(film)2400-3500(br,CO2H),1695(C=O),1620,1605,1585,1440,1290,1245,1170,915,885,755,725,and 700cm-1;MS(DCI)m/e 323(MH+).305(M+-OH).Anal.Calcd for C20H18O4·0.1H2O:C,74.11;H,5.66.Found:C,74.08;H,5.61.
對(duì)于(2Z),(4Z)-4-(3-羧基苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸(11g)量度=2.21mmol,產(chǎn)率=75%;
1H NMR(300MHz,CD3OD)δ7.89(dt,J=2,8Hz,1H,4-ArH),7.82(t,J=2Hz,1H,4-ArH),7.34(t,J=8Hz,1H,4-ArH),7.15(m,2H,4-ArH and 7-ArH),6.99(d,J=2Hz,1H,7-ArH),6.80(dd,J=2,8Hz,1H,7-ArH),6.58(dd,J=1,12Hz,1H,CH=CHCO2),6.06(t,J=8Hz,1H,C=CH),5.75(d,J=12Hz,1H,CH=CHCO2),2.61(t,J=8Hz,2H,ArCH2),2.29(q,J=8Hz,2H,ArCH2CH2),1.65(s,4H,CH2CH2),1.23(s,6H,2×CH3),and 1.20(s,6H,2×CH3);13C NMR(75MHz,CD3OD)δ170.10(C=O),169.78(C=O),145.62,143.35,143.25,139.75,139.46,139.04,138.28,134.96,131.69,129.37,129.08,127.72,127.52,127.48,126.85,120.99,36.37,36.32,36.19,35.06,34.85,32.67,32.34,and 31.43;IR(film)2400-3500(br,CO2H),2960,2925,2860,1695(C=O),and 755cm-1;MS(DCI)m/e 434(M+2H)+.Anal.Calcd for C28H32O4·0.1H2O:C,77.43;H,7.47.Found:C,77.22;H,7.47.
對(duì)于(2Z),(4Z),(6E)-4-(3-羧基苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4,6-辛三烯酸(11h);量度=0.30mmol,產(chǎn)率=67%;
UVmax(CH3OH)348nm(ε=33,200);1H NMR(300MHz,CD3OD)1H NMR(300MHz,CD3OD)δ7.94-7.98(m,2H,4-ArH),7.43-7.47(m,2H,4-ArH),7.05-7.25(m,4H,3×7-ArH and C=CH),6.73(d,J=12Hz,1H,CH=CHCO2),6.48(brd,J=12Hz,1H,C=CH),5.84(d,J=12Hz,1H,CH=CHCO2),2.25(d,J=1.5Hz,3H,C=CCH3),1.65(s,4H,CH2CH2),1.22(s,6H,2×CH3),and 1.18(s,6H,2×CH3);13C NMR(75MHz,CD3OD)δ170.56(C=O),169.89(C=O),145.71,142.66,142.46,141.08,140.26,138.66,135.20,133.36,132.39,131.89,129.58,129.21,127.59,124.76,124.07,123.78,121.58,36.24,36.13,35.19,35.03,32.21,32.10,and 16.19(C=CCH3);IR(film)2400-3600(br,CO2H),2960,2925,2860,1690(C=O),1585,1445,1295,1255,and 1225cm-1;MS(DCI)m/e 445(MH+),399(M+-CO2H).Anal.Calcd for C29H32O4·0.33H2O:C,77.30;H,7.31.Found:C,77.36;H,7.20.
對(duì)于(2Z),(4Z)-4-(3-羧基苯基)-7-[4-(1-金剛烷基)-3-甲氧苯基]-2,4-庚二烯酸(11i)量度=0.54mmol,產(chǎn)率=100%;
UVmax(CH3OH)280nm(ε=8,600),270nm(ε=10,500);1H NMR(300MHz,CD3OD)δ7.90(dt,J=2,8Hz,1H,4-ArH),7.84(t,J=2Hz,1H,4-ArH),7.35(t,J=8Hz,1H,4-ArH),7.17(dt,J=2,8Hz,1H,4-ArH),7.01(d,J=8Hz,1H,7-ArH),6.56-6.61(m,3H,2×7-ArH and CH=CHCO2),6.05(t,J=8Hz,1H,C=CH),5.76(d,J=12Hz,1H,CHCO2),3.72(s,3H,OCH3),2.64(t,J=8Hz,2H,ArCH2),2.33(q,J=8Hz,2H,ArCH2CH2),2.06(brs,6H,adamantyl),2.01(brs,3H,adamantyl),and 1.73(brs,6H,adamantyl);13C NMR(75MHz,CD3OD)δ170.10(C=O),169.78(C=O),160.11,143.20,141.32,139.76,139.06,138.07,137.13,134.96,131.72,131.59,129.38,129.12,127.15,121.49,121.07,113.16,55.34(OCH3),41.94,38.28,37.74,36.08,32.42,and 30.63;IR(KBr)3420(br,CO2H),2905,2850,1695(C=O),1450,1415,1290,and 1245cm-1;MS(DCI)m/e 487(MH+)and 443(MH+-CO2H).Anal.Calcd for C31H34O5·0.33H2O:C,75.58;H,7.09.Found:C,75.59;H,7.02.
對(duì)于(2Z),(4Z)-4-(3-羧基苯基)-7-[3-(1-金剛烷基)-4-甲氧苯基]-2,4-庚二烯酸(11j)量度=0.21mmol,產(chǎn)率=87%;
1H NMR(300MHz,CD3OD)δ7.81(d,J=8Hz,1H,4-ArH),7.68(s,1H,4-ArH),7.39(t,J=8Hz,1H,4-ArH),7.24(d,J=8Hz,1H,4-ArH),6.77-6.88(m,3H,7-ArH),6.55(d,J=13Hz,1H,CH=CHCO2),6.00(t,J=7Hz,C=CH),5.76(d,J=12Hz,1H,CH=CHCO2),3.71(s,3H,OCH3),2.55(t,J=8Hz,2H,ArCH2),2.22(q,J=8Hz,2H,ArCH2CH2),1.95(m,9H,adamantyl),and 1.68(s,6H,adamantyl);13C NMR(75MHz,CD3OD)δ167.29(C=O),167.01(C=O),156.67,141.05,138.05,137.26,137.13,136.19,133.14,132.58,130.54,129.67,128.05,127.83,126.30,126.12,121.06,111.92,55.13(OCH3),40.12,36.57,36.24,34.34,31.23,and 28.38;IR(KBr)2400-3500(br,CO2H),2905,2850,1695(C=O),1495,1445,1285,1260,and 1235cm-1;MS(DCI)m/e 487(MH+),135(C10H15+).Anal.Calcd for C31H34O5:C,76.52;H,7.04.Found:C,76.19;H,7.14.
實(shí)施例10b合成11k化合物對(duì)于(2Z),(4Z)-3-甲基-4-(3-羧基苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2,4-戊二烯酸(11k);將叔丁酸鉀(1.40g,12.5mmol)的THF(40ml)懸浮液在氮?dú)猸h(huán)境下冷卻至-5℃。向該淤漿中加入4-(3-甲氧羰基苯基)-3-甲基-2-丁烯酸酯(Tram-posch,K.M.et al.Biochemical and Bcophysical Research Communications 1992,189,272)(1.66g,6.00mmol)的THF(5ml)溶液。于0℃攪拌該混合物30min。向反應(yīng)混合物中緩慢加入5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽醛(3b)(1.33g,5.00mmol)的THF(5ml)溶液。于0℃攪拌30min后,加入4ml水。繼續(xù)攪拌3h后,用1NHCl酸化溶液至PH2。將該酸性溶液倒入分液漏斗并與乙醚一起物藥。有機(jī)相用水和鹽水洗滌,于無水硫酸鎂上干燥,過濾并濃縮。利用梯度洗脫(二氯甲烷-5%甲醇/二氯甲烷),通過硅膠塞純化粗產(chǎn)物。除去溶劑后得到一油狀物,將其溶于乙腈以沉淀1k,為白色固體(1.34g,55%);
mp 186-7℃;UVmax(CH3CH2OH)318nm(ε=16,000),222nm(ε=45,000);1H NMR(300MHz,one drop of DMSO-d6in CDCl3)δ7.95(s,1H,ArH),7.88(d,J=8Hz,1H,ArH),7.54(d,J=13Hz,2H,ArH),7.39-7.42(m,2H,ArH),7.31(d,J=8.5Hz,1H,ArH),7.20(t,J=8Hz,1H,ArH),6.85(dd,J=8.5,1Hz,1H,ArH),6.64(s,1H,ArCH=C),5.82(d,J=1Hz,1H,C=CHCO2),1.84(s,3H,C=CCH3),1.68(s,4H,CH2CH2),and 1.29(s,12H,4×CH3);13C NMR(75MHz,CDCl3)δ168.96(C=O),168.80(C=O),156.12,144.38,144.25,140.50,138.24,134.70,133.18,131.52,130.85,130.78,130.71,128.86,128.42,128.30,128.15,126.28,124.88,124.41,119.55,34.91,34.40,34.36,32.33,and 24.19;IR(KBr)2965,2925,2860,1690(C=O),1650,1465,1360,1300,1250,960cm-1;MS(DCI)m/e 469(MH+),425.Anal.Calcd for C31H32O4:C,79.48;H,6.84.Found:C,79.30;H,7.08.
實(shí)施例11合成化合物12的一般方法向醇5的二氯甲烷溶液(0.1M)中一次性加入二氧化錳(5∶1MnO2/乙醇)。將反應(yīng)混合物于室溫下在塞好的燒瓶中攪拌4-40h。根據(jù)需要繼續(xù)加入MnO2以使反應(yīng)完全。通過1英寸硅藻土塞過濾棕色淤漿,并用二氯甲烷洗滌收集的固體。真空濃縮濾液,所得醛產(chǎn)物不經(jīng)純化直接使用。
對(duì)于(Z)-2-(3-三氟甲苯基)-3-(4-癸氧苯基)-2-丙烯醛(12a)量度=5.9mmol,產(chǎn)率=90%;
1H NMR(300MHz,CDCl3)δ9.69(s,1H,CHO),7.63(d,J=8Hz,1H,2-ArH),7.53(t,J=8Hz,1H,2-ArH),7.47(s,1H,C=CH),7.38(d,J=8Hz,1H,2-ArH),7.36(s,1H,2-ArH),7.09(dt,J=3,9Hz,2H,3-ArH),6.73(dt,J=3,9Hz,2H,3-ArH),3.91(t,J=7Hz,2H,ArOCH2),1.73(quint,J=7Hz,2H,ArOCH2CH2),1.16-1.40(m,14H,7×CH2),0.85(t,J=7Hz,3H,CH3);13C NMR(75MHz,CDCl3)δ193.14(C=O),161.31(3-ArC),151.30,138.01,134.67,133.10,132.74(3-ArC),129.34,126.49(q,J3c,f=4Hz,2-ArC),125.79,124.98(q,J3c,f=4Hz,2-ArC),114.69(3-ArC),68.19(ArOCH2),40.60,31.87,29.52,29.30,29.04,25.92,and 14.10;IR(KBr)2960,2920,2870,2850,1675(C=O),1600,1570,1510,1475,1425,1325,1310,1260,1180,and 1165cm-1;MS(DCI)m/e 433(MH+).
對(duì)于(Z)-2-(3-三氟甲苯基)-3-(3-癸氧苯基)-2-丙烯醛(12b)量度=1.8mmol,產(chǎn)率=95%;
1H NMR(300MHz,CDCl3)δ9.75(s,1H,CHO),7.62(d,J=8Hz,1H,2-ArH),7.56(t,J=8Hz,1H,2-ArH),7.48(s,1H,2-ArH),7.41(s,1H,C=CH),7.38(d,J=8Hz,1H,2-ArH),7.15(t,J=8Hz,1H,3-ArH),6.85(dt,J=2,8Hz,1H,3-ArH),6.78(d,J=8Hz,1H,3-ArH),6.58(t,J=2Hz,1H,3-ArH),3.57(t,J=7Hz,2H,ArOCH2),1.57-1.65(m,2H,ArOCH2CH2),1.21-1.37(m,14H,7×CH2),and 0.87(t,J=7Hz,3H,CH3);13C NMR(75MHz,CDCl3)δ193.16(C=O),158.98(3-ArC),151.28,140.32,134.50,134.37,134.00,129.68,129.34,126.50(q,J3c,f=4Hz,2-ArC),125.04(q,J3c,f=4Hz,2-ArC),123.60,118.21,115.02,67.78(ArOCH2),31.89,29.53,29.31,29.27,28.98,25.83,22.68,and 14.11;IR(film)2925,2855,1690(C=O),1580,1325,1270,and 1165cm-1;MS(DCI)m/e 433(MH+).
對(duì)于(Z)-2-(3-三氟甲苯基)-3-(2-癸氧苯基)-2-丙烯醛(12c)量度=2.0mmol,產(chǎn)率=93%;
1H NMR(300MHz,CDCl3)δ9.77(s,1H,CHO),7.87(s,1H,C=CH),7.58(d,J=8Hz,1H,2-ArH),7.39-7.47(m,2H,2-ArH),7.38(d,J=8Hz,1H,2-ArH),7.25(dt,J=2,8Hz,1H,3-ArH),6.92(d,J=8Hz,1H,3-ArH),6.77(dd,J=2,8Hz,1H,3-ArH),6.61(t,J=8Hz,1H,3-ArH),4.03(t,J=7Hz,2H,ArOCH2),1.85(quint,J=7Hz,2H,ArOCH2CH2),1.22-1.54(m,14H,7×CH2),and 0.87(t,J=7Hz,3H,CH3);13C NMR(75MHz,CDCl3)δ193.46(C=O),157.90(3-ArC),146.68,139.54,134.30,133.16,132.11,130.30,129.04,126.58(q,J3c,f=4Hz,2-ArC),124.82(q,J3c,f=4Hz,2-ArC),122.47,119.97,111.95,68.62(OCH2),31.89,29.59,29.57,29.37,29.32,29.13,26.12,22.68,and 14.11;IR(film)2925,2855,1690(C=O),1600,1455,1325,1250,and 1165cm-1;MS(DCI)m/e 433(MH+).
對(duì)于(Z)-2-(3-三氟甲苯基)-3-[4-(2E),(6E)-3,7-二甲基-辛-2,6-二烯氧]苯基)-2-丙烯醛(12d)量度=1.35mmol,產(chǎn)率=92%;
1H NMR(300MHz,CDCl3)δ9.70(s,1H,CHO),7.63(d,J=8Hz,1H,2-ArH),7.53(t,J=8Hz,1H,2-ArH),7.47(s,1H,ArCH=C),7.39(d,J=8Hz,1H,2-ArH),7.36(s,1H,2-ArH),7.10(dt,J=3,9Hz,2H,3-ArH),6.75(dt,J=3,9Hz,2H,3-ArH),5.41(dt,J=1,7Hz,1H,C=CHCH2O),5.03-5.06(m,1H,CH=C(CH3)2),4.51(d,J=7Hz,2H,ArOCH2),2.03-2.12(m,4H,C=CHCH2CH2),and 1.55-1.69(m,9H,3×CH3);13C NMR(75MHz,CDCl3)δ193.11(C=O),161.06(3-ArC),151.22,141.89,138.07,134.66,133.10,132.71(3-ArC),131.89,131.48,129.34,126.52(q,J3c,f=4Hz,2-ArC),125.90,124.99(q,J3c,f=4Hz,2-ArC),123.65,118.74,114.92(3-ArC),65.03(ArOCH2),39.48,26.22,25.66,17.67,and 16.67;IR(KBr)2970,2915,2890,1675,1600,1570,1510,1425,1325,1310,1255,1180,1160,and 1115cm-1;MS(DCI)m/e 429(MH+).
對(duì)于(Z)-2-(3-三氟甲苯基)-3-(3,4-雙癸氧苯基)-2-丙烯醛(12e)量度=2.11mmol,產(chǎn)率=94%;
1H NMR(300MHz,CDCl3)δ9.72(s,1H,CHO),7.40-7.68(m,4H,2-ArH),7.37(s,1H,C=CH),6.91(dd,J=2,8Hz,1H,3-ArH),6.79(d,J=8Hz,1H,3-ArH),6.50(d,J=2Hz,1H,3-ArH),4.00(t,J=7Hz,2H,CH2OAr),3.45(t,J=7Hz,2H,CH2OAr),1.75-1.88(m,2H,CH2CH2OAr),1.55-1.67(m,2H,CH2CH2OAr),1.20-1.48(m,28H,14×CH2),and 0.83-0.95(m,6H,2×CH3).
對(duì)于(Z)-2-(3-三氟甲苯基)-3-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2-丙烯醛(12f)量度=1.6mmol,產(chǎn)率=78%;
1H NMR(300MHz,CDCl3)δ9.80(s,1H,CHO),7.75(s,1H,ArH),7.64-7.68(m,3H,ArH),7.58(s,1H,ArH),7.45-7.55(m,3H,2×ArH and C=CH),4.42(d,J=8Hz,1H,ArH),6.90(dd,J=2,9Hz,1H,ArH),1.74(s,4H,CH2CH2),and 1.35(brs,12H,4×CH3);13C NMR(75MHz,CDCl3)δ193.26(C=O),151.94,147.10,145.58,139.48,133.30,132.41,132.20,131.33,130.22,129.22,127.41,126.73,125.95,125.15,124.91,34.86(CH2CH2),34.81,34.61,and 32.43 and 32.38(4×CH3);IR(KBr)2960,2930,1685(C=O),1605,1325,1165,and 1125 cm-1.
對(duì)于(Z)-2-(3-三氟甲苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-戊烯醛(12g)量度=1.39mmol,產(chǎn)率=89%;
1H NMR(300MHz,CDCl3)δ9.80(s,1H,CHO),7.50(brd,J=8Hz,1H,2-ArH),7.39(t,J=8Hz,1H,2-ArH),7.31(s,1H,2-ArH),7.21(d,J=8Hz,1H,2-ArH),7.10(d,J=8Hz,1H,5-ArH),7.04(d,J=2Hz,1H,5-ArH),6.88(dd,J=2,8Hz,1H,5-ArH),6.82(t,J=8Hz,1H,C=CH),2.79(t,J=8Hz,2H,ArCH2),2.65(q,J=8Hz,2H,ArCH2CH2),1.65(brs,4H,CH2CH2),1.25(s,6H,2×CH3),and 1.22(s,6H,2×CH3).
對(duì)于(Z)-2-(4-氟苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-戊烯醛(12h)量度=1.94mmol,產(chǎn)率=95%;
1H NMR(300MHz,CDCl3)δ9.61(s,1H,CHO),7.24(d,J=8Hz,1H,5-ArH),6.98-7.08(m,3H,ArH),6.85-6.93(m,3H,ArH),6.76(t,J=8Hz,1H,C=CH),2.79(t,J=8Hz,2H,ArCH2),2.65(q,J=8Hz,2H,ArCH2CH2),1.67(brs,4H,CH2CH2),1.25(s,6H,2×CH3),and 1.23(s,6H,2×CH3).
對(duì)于(Z)-2-(3-氟苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-戊烯醛(12i)量度=2.73mmol,產(chǎn)率=94%;
1H NMR(300MHz,CDCl3)δ9.59(s,1H,CHO),7.22-7.31(m,2H,1×2-ArH and 1×5-ArH),7.03(d,J=2Hz,1H,5-ArH),6.98(apparent tt,J=2,8Hz,1H,2-ArH),6.88(dd,J=2,8Hz,1H,5-ArH),6.79(t,J=8Hz,1H,C=CH),6.72(dd,J=2,8Hz,1H,2-ArH),6.63(apparent dt,J=2,8Hz,1H,2-ArH),2.79(t,J=8Hz,2H,ArCH2),2.64(q,J=8Hz,2H,ArCH2CH2),1.67(brs,4H,CH2CH2),1.27(s,6H,2×CH3),and 1.24(s,6H,2×CH3).
對(duì)于(Z)-2-苯基-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-戊烯醛(12j)量度=0.78mmol,產(chǎn)率=95%;
1H NMR(300MHz,CDCl3)δ9.61(s,1H,CHO),7.28-7.38(m,3H,2-ArH),7.22(d,J=8Hz,1H,5-ArH),7.05(d,J=2Hz,1H,5-ArH),6.92-7.00(m,2H,2-ArH),6.88(dd,J=2,8Hz,1H,5-ArH),6.75(t,J=8Hz,1H,C=CH),2.78(t,J=8Hz,2H,ArCH2),2.66(q,J=8Hz,2H,ArCH2CH2),1.66(brs,4H,CH2CH2),1.26(s,6H,2×CH3),and 1.24(s,6H,2×CH3).
對(duì)于(Z)-2-(3-三氟甲苯基)-5-[3-(1-金剛烷基)-4-甲氧苯基]-2-戊烯醛(12k)量度=0.60mmol,產(chǎn)率=100%;
1H NMR(300MHz,CDCl3)δ9.63(s,1H,CHO),7.61(d,J=8Hz,1H,2-ArH),7.50(t,J=8Hz,1H,2-ArH),7.30(s,1H,2-ArH),7.19(d,J=8Hz,1H,2-ArH),6.96(d,J=2Hz,1H,5-ArH),6.92(dd,J=2,8Hz,1H,5-ArH),6.85(t,J=8Hz,1H,C=CH),6.80(d,J=8Hz,1H,5-ArH),3.83(s,3H,OCH3),2.80(t,J=8Hz,2H,ArCH2),2.65(q,J=8Hz,2H,ArCH2CH2),2.07(s,9H,adamantyl),and 1.78(s,6H,adamantyl).
對(duì)于(Z)-2-(3-苯基)-5-[3-(1-金剛烷基)-4-甲氧苯基]-2-戊烯醛(12l)量度=0.96mmol,產(chǎn)率=89%,約6∶1Z/E異構(gòu)體混合物;
1H NMR(300MHz,CDCl3)δ(Z-isomer)9.60(s,1H,CHO),7.33-7.39(m,3H,2-ArH),7.03-7.07(m,2H,2-ArH),6.98(d,J=2Hz,1H,5-ArH),6.93(dd,J=2,8Hz,1H,5-ArH),6.78(d,J=8Hz,1H,5-ArH),6.75(t,J=8Hz,1H,C=CH),3.80(s,3H,OCH3),2.79(t,J=8Hz,2H,ArCH2),2.64(q,J=8Hz,2H,ArCH2CH2),2.02(s,9H,adamantyl),and 1.76(s,6H,adamantyl).
對(duì)于(Z)-2-(3-三氟甲苯基)-5-[4-(1-金剛烷基)-3-甲氧苯基]-2-戊烯醛(12m)量度=1.06mmol,產(chǎn)率=87%;
1H NMR(300MHz,CDCl3)δ9.58(s,1H,CHO),7.57(d,J=8Hz,1H,2-ArH),7.45(t,J=8Hz,1H,2-ArH),7.30(s,1H,2-ArH),7.09(m,2H,2-ArH and 5-ArH),6.82(t,J=7Hz,1H,C=CH),6.65(dd,J=1,8Hz,1H,5-ArH),6.57(d,J=2Hz,1H,5-ArH),3.76(s,3H,OCH3),2.79(t,J=8Hz,2H,ArCH2),2.63(q,J=8Hz,2H,ArCH2CH2),2.04(s,9H,adamantyl),and 1.76(s,6H,adamantyl).
對(duì)于(Z)-2-苯基-5-[4-(1-金剛烷基)-3-甲氧苯基]-2-戊烯醛(12n)量度=3.48mmol,產(chǎn)率=86%;
1H NMR(300MHz,CDCl3)δ9.62(s,1H,CHO),7.30-7.40(m,3H,2-ArH),7.11(d,J=8Hz,1H,5-ArH),6.96-7.03(m,2H,2-ArH),6.75(t,J=8Hz,1H,C=CH),6.68(dd,J=2,8Hz,1H,5-ArH),6.58(d,J=2Hz,1H,5-ArH),3.77(s,3H,OCH3),2.79(t,J=8Hz,2H,ArCH2),2.68(q,J=8Hz,2H,ArCH2CH2),2.07(brs,9H,adamantyl),and 1.76(brs,6H,adamantyl).
對(duì)于(Z)-2-(3-三氟甲苯基)-5-[2-(1-金剛烷基)-4-甲氧苯基]-2-戊烯醛(12o)量度=0.30mmol,產(chǎn)率=100%;
1H NMR(300MHz,CDCl3)δ9.65(s,1H,CHO),7.60(d,J=8Hz,1H,2-ArH),7.49(t,J=8Hz,1H,2-ArH),7.33(s,1H,2-ArH),7.26(m,1H,2-ArH),6.97(d,J=8Hz,1H,5-ArH),6.89(m,2H,5-ArH and C=CH),6.67(dd,J=3,8Hz,1H,5-ArH),3.77(s,3H,OCH3),3.08(t,J=8Hz,2H,ArCH2),2.65(q,J=8Hz,2H,ArCH2CH2),2.04(s,3H,adamantyl),1.94(s,6H,adamantyl),and 1.74(m,6H,adamantyl).
對(duì)于(Z)-2-(3-三氟甲苯基)-3-[4-(1-金剛烷基)-3-甲氧苯基]-2-丙烯醛(12p)量度=2.13mmol,產(chǎn)率=94%;
1H NMR(300MHz,CDCl3)δ9.74(s,1H,CHO),7.65(d,J=8Hz,1H,2-ArH),7.57(t,J=8Hz,1H,2-ArH),7.51(s,1H,2-ArH),7.41(m,2H,2-ArH and C=CH),7.15(d,J=8Hz,1H,3-ArH),6.88(dd,J=2,8Hz,1H,3-ArH),6.49(d,J=2Hz,1H,3-ArH),3.34(s,3H,OCH3),2.00(s,9H,adamantyl),and 1.72(s,6H,adamantyl).
對(duì)于(Z)-2-(3-三氟甲苯基)-5-[4-(1-金剛烷基)-3-叔丁基二甲基甲硅烷氧苯基]-2-戊烯醛(12q)量度=1.43mmol,產(chǎn)率=90%;
1H NMR(300MHz,CDCl3)δ9.60(s,1H,CHO),7.59(d,J=8Hz,1H,2-ArH),7.46(t,J=8Hz,1H,2-ArH),7.31(s,1H,2-ArH),7.11(m,2H,2-ArH and 5-ArH),6.82(t,J=7Hz,1H,HC=CCHO),6.65(dd,J=1,8Hz,1H,5-ArH),6.52(d,J=2Hz,1H,5-ArH),2.73(t,J=7Hz,2H,CH2Ar),2.61(q,J=7Hz,2H,ArCH2CH2),2.07(s,9H,adamantyl),1.76(s,6H,adamantyl),1.01(s,9H,t-butyl),and 0.28(s,6H,Si(CH3)2).
實(shí)施例12合成化合物13的一般方法在氬氣環(huán)境下,將18-冠-6-(5當(dāng)量)和雙(2,2,2-三氟乙基)(甲氧羰基甲基)膦酸酯(1.1當(dāng)量)的無水四氫呋喃溶液冷卻至-78℃。然后依次加入雙三甲基甲硅烷基氨化鉀(0.5M于甲苯,1.1當(dāng)量)溶液和醛12(1當(dāng)量)的四氫呋喃溶液(0.05M的終濃度)。加熱反應(yīng)混合物至室溫,倒入裝有乙醚和飽和氯化銨溶液的分液漏斗中。攪拌分層,乙醚層用飽和氯化鈉溶液進(jìn)一步洗滌,于無水硫酸鎂上干燥,過濾,濃縮。通過柱層析純化(40∶1硅膠/粗產(chǎn)物;用3-5%乙酸乙酯/己烷洗脫),得到目的化合物。
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-5-(4-癸氧苯基)-2,4-戊二烯酸甲酯(13a)量度=2.8mmol,產(chǎn)率=75%;
1H NMR(300MHz,CDCl3)δ7.36-7.53(m,4H,4-ArH),6.78-6.86(m,3H,2×5-ArH and C=CH),6.60-6.66(m,3H,2×5-ArH and CH=CHCO2),5.81(d,J=16Hz,1H,CH=CHCO2),3.86(t,J=6Hz,2H,ArOCH2),3.25(s,3H,CO2CH3),1.71(quintet,J=6Hz,2H,ArOCH2CH2),1.24-1.50(m,14H,7×CH2),and 0.85(t,J=6Hz,3H,CH3);13C NMR(75MHz,CDCl3)δ166.82(C=O),159.02(5-Ar),142.64,139.32,136.11,134.47,133.26,131.54,131.03(5-ArC),129.01,127.73,126.42(q,J3c,f=4Hz,4-ArC),124.13(q,J3c,f=4Hz,4-ArC),119.68,114.18(5-ArC),67.96(ArOCH2),51.22(CO2CH3),31.87,29.53,29.35,29.30,29.14,25.97,22.66,and 14.10;IR(film)2925,2855,1730(C=O),1600,1510,1325,1310,1255,1175,and 1165cm-1;MS(DCI)m/e 489(MH+).
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-5-(3-癸氧苯基)-2,4-戊二烯酸甲酯(13b)量度=0.90mmol,產(chǎn)率=95%;
1H NMR(300MHz,CDCl3)δ7.51(dd,J=2,7Hz,1H,4-ArH),7.48(s,1H,4-ArH),7.36-7.44(m,2H,4-ArH),7.03(t,J=8Hz,1H,5-ArH),6.84(brs,1H,C=CH),6.66-6.70(m,1H,5-ArH),6.66(dd,J=2,12Hz,1H,CH=CHCO2),6.54(d,J=8Hz,1H,5-ArH),6.37(t,J=2Hz,1H,5-ArH),5.87(d,J=12Hz,1H,CH=CHCO2),3.56(t,J=7Hz,2H,ArOCH2),3.28(s,3H,CO2CH3),1.55-1.65(m,2H,ArOCH2CH2),1.21-1.35(m,14H,7×CH2),and 0.87(t,J=7Hz,3H,CH3);13C NMR(75MHz,CDCl3)δ166.65(C=O),158.72(5-ArC),142.13,139.06,136.60,135.92,133.26,131.08,130.66,129.13,129.01,126.42(q,J3c,f=4Hz,4-ArC),124.18(q,J3c,f=4Hz,4-ArC),122.30,120.76,115.29,114.42,67.66(ArOCH2),51.28(CO2CH3),31.89,29.55,29.31,25.88,22.68,and 14.11;IR(film)2925,1730(C=O),1435,1325,1265,and 1165 cm-1;MS(DCI)m/e 489(MH+).
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-5-(2-癸氧苯基)-2,4-戊二烯酸甲酯(13c)量度=0.92mmol,產(chǎn)率=72%;12∶1Z/E異構(gòu)體混合物;
1H NMR(300MHz,CDCl3)δ7.42-7.57(m,2H,4-ArH),7.33-7.37(m,2H,4-ArH),7.07-7.13(m,2H,5-ArH and C=CH),6.80(d,J=8Hz,1H,5-ArH),6.72(dd,J=2,12Hz,1H,CH=CHCO2),6.48-6.70(m,2H,5-ArH),5.88(d,J=12Hz,1H,CH=CHCO2),3.95(t,J=7Hz,2H,ArOCH2),3.28(s,3H,CO2CH3),1.78(quint,J=7Hz,2H,ArOCH2CH2),1.21-1.47(m,14Hz,7×CH2),and 0.87(t,J=7Hz,3H,CH3);13C NMR(75MHz,CDCl3)δ166.77(C=O),157.29(5-ArC),142.93,139.27,136.00,133.11,131.55,130.23,129.21,128.68,126.30(q,J3c,f=4Hz,4-ArC),124.71,123.89(q,J3c,f=4Hz,4-ArC),120.43,119.73,68.38(ArOCH2),51.18(CO2CH3),31.90,29.58,29.38,29.33,29.19,26.07,22.67,and 14.11;IR(film)2925,2855,1730(C=O),1325,1250,and 1165cm-1;MS(DCI)m/e 489(MH+).
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-5-[4-(2E),(6E)-3,7-二甲基-辛-2,6-二烯-氧]苯基)-2,4-戊二烯酸甲酯(13d)量度=1.20mmol,產(chǎn)率=62%;
1H NMR(300MHz,CDCl3)δ7.51-7.53(m,1H,4-ArH),7.47(s,1H,4-ArH),7.38-7.42(m,2H,4-ArH),6.79-6.84(m,3H,2×5-ArH and C=CH),6.62-6.68(m,3H,2×5-ArH and CH=CHCO2),5.81(d,J=12Hz,1H,CH=CHCO2),5.41(t,J=7Hz,1H,C=CHCH2O),5.03-5.06(m,1H,CH=C(CH3)2),4.45(d,J=7Hz,2H,ArOCH2),3.26(s,3H,CO2CH3),2.02-2.08(m,4H,C=CHCH2CH2),and 1.55-1.68(m,9H,3×CH3);13C NMR(75MHz,CDCl3)δ166.80(C=O),158.77(5-ArC),142.64,141.37,139.30,136.04,134.53,133.26,131.83,131.02(5-ArC),129.02,127.86,126.40(q,J3c,f=4Hz,4-ArC),124.12(q,J3c,f=4Hz,4-ArC),123.74,119.73,119.16,114.41(5-ArC),64.84(ArOCH2),51.22(CO2CH3),39.50,26.26,25.67,17.67,and 16.64;IR(film)2925,1725(C=O),1670,1600,1510,1325,1310,1250,1165,and 1125cm-1;MS(DCI)m/e 485(MH+).
對(duì)于(2Z),(4Z)-4-(3-三氟甲基苯基)-5-(3,4-雙癸氧苯基)-2,4-戊二烯酸甲酯(13e)量度=1.40mmol,產(chǎn)率=94%;
1H NMR(300MHz,CDCl3)δ7.39-7.53(m,4H,4-ArH),6.81(s,1H,C=CH),6.57-6.67(m,3H,2×5-ArH and CH=CHCO2),6.26(d,J=2Hz,1H,5-ArH),5.79(d,J=12Hz,1H,CH=CHCO2),3.91(t,J=7Hz,2H,CH2OAr),5.79(d,J=12Hz,1H,CH=CHCO2),3.91(t,J=7Hz,2H,CH2OAr),3.43(t,J=7Hz,2H,CH2OAr),3.24(s,3H,CO2CH3),1.70-1.79(m,2H,CH2CH2OAr),1.54-1.61(m,2H,CH2CH2OAr),1.24-1.45(m,28H,14×CH2),and 0.83-0.89(m,6H,2×CH3);13C NMR(75MHz,CDCl3)δ166.81(C=O),149.23,148.33,142.31,139.58,136.64,134.49,133.46,131.00(q,J2c,f=38Hz,2-ArC),129.12,128.08,126.57(q,J3c,f=4Hz,2-ArC),124.02(q,J3c,f=4Hz,2-ArC),124.00(q,J1c,f=273Hz,CF3),123.78,119.47,113.82,112.79,69.00(CH2O),68.50(CH2O),51.21(CO2CH3),31.90,29.58,29.32,29.12,29.01,25.94,25.80,22.67,and 14.10;IR(KBr)2925,2855,1730(C=O),1595,1510,1470,1435,1325,1310,1270,1240,1200,1165,1130,1095,1070,1000,800,and 705cm-1;MS(DCI)m/e 645(MH+).
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2,4-戊二烯酸甲酯(13f);量度=1.3mmol,產(chǎn)率=82%;
1H NMR(300MHz,CDCl3)δ7.62(s,1H,ArH),7.52-7.57(m,3H,ArH),7.45(s,1H,ArH),7.36-7.39(m,3H,ArH),7.02(s,1H,C=CH),6.74(dd,J=2,9Hz,1H,ArH),6.72(dd,J=1,12Hz,1H,CH=CHCO2),5.89(d,J=12Hz,1H,CH=CHCO2),3.28(s,3H,CO2CH3),1.72(s,4H,CH2CH2),and 1.33(s,12H,4×CH3);IR(KBr)3010,2960,2930,2865,1730(C=O),1620,1465,1435,1320,1310,1240,1210,1170,and 1135cm-1;MS(DCI)m/e 492(MH+).
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸甲酯(13g)量度=0.74mmol,產(chǎn)率=90%;
1H NMR(300MHz,CDCl3)δ7.48(brd,J=8Hz,1H,4-ArH),7.39(t,J=8Hz,1H,4-ArH),7.36(s,1H,4-ArH),7.18(d,J=8Hz,1H,4-ArH),7.17(d,J=8Hz,1H,7-ArH),6.98(d,J=2Hz,1H,7-ArH),6.82(dd,J=2,8Hz,1H,7-ArH),6.54(d,J=12Hz,1H,CH=CHCO2),6.07(t,J=8Hz,1H,C=CH),5.72(d,J=12Hz,1H,CH=CHCO2),3.18(s,3H,CO2CH3),2.63(t,J=8Hz,2H,ArCH2),2.32(q,J=8Hz,2H,ArCH2CH2),1.64(brs,4H,CH2CH2),1.23(s,6H,2×CH3),and 1.21(s,6H,2×CH3);13C NMR(75MHz,CDCl3)δ166.50(C=O),144.76,142.58,141.77,139.15,138.69,137.73,136.97,132.51,128.50,126.52,126.39,125.79(q,J3c,f=4Hz,4-ArC),125.61,123.75(q,J3c,f=4Hz,4-ArC),119.23,51.08(CO2CH3),35.12,35.07,34.13,33.94,31.86,31.80,and 31.07;IR(film)2960,2925,2860,1730(C=O),1495,1460,1435,1385,1365;1325,1310,1280,1165,1125,1095,1070,825,800,and 760cm-1;MS(DCI)m/e 471(MH+).
對(duì)于(2Z),(4Z)-4-(4-氟苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸甲酯(13h)量度=0.96mmol,產(chǎn)率=82%;
1H NMR(300MHz,CDCl3)δ7.16(d,J=8Hz,1H,7-ArH),6.91-6.98(m,5H,4×4-ArH and 1×7-ArH),6.82(dd,J=2,8Hz,1H,7-ArH),6.52(d,J=13Hz,1H,CH=CHCO2),5.99(t,J=8Hz,1H,C=CH),5.69(d,J=12Hz,1H,CH=CHCO2),3.24(s,3H,CO2CH3),2.61(t,J=8Hz,2H,ArCH2),2.32(q,J=8Hz,2H,ArCH2CH2),1.64(brs,4H,CH2CH2),1.24(s,6H,2×CH3),and 1.22(s,6H,2×CH3);13C NMR(75MHz,CDCl3)δ166.97,166.57(d,J1c,f=246Hz,4-ArC),144.07,142.39,138.09,137.99,137.23,130.71(d,J3c,f=8Hz,4-ArC),126.44,125.67,118.84,114.79(J2c,f=21Hz,4-ArC),51.15(CO2CH3),35.16,35.14,35.09,34.14,33.94,31.89,31.84 and 31.06;IR(film)2960,2925,2860,1730(C=O),1600,1510,1455,1435,1360,1220,1195,1170,1160,840,and 820cm-1;MS(DCI)m/e 421(MH+).
對(duì)于(2Z),(4Z)-4-(3-氟苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸甲酯(13i)量度=1.35mmol,產(chǎn)率=91%;
1H NMR(300MHz,CDCl3)δ7.21-7.27(m,1H,4-ArH),7.17(d,J=2Hz,1H,7-ArH),7.00(d,J=2Hz,1H,7-ArH),6.80-6.85(m,3H,2×4-ArH and 1×7-ArH),6.71(apparent dt,J=2,8Hz,1H,4-ArH),6.51(d,J=12Hz,1H,CH=CHCO2),6.01(t,J=8Hz,1H,C=CH),5.71(d,J=12Hz,1H,CH=CHCO2),3.27(s,3H,CO2CH3),2.62(t,J=8Hz,2H,ArCH2),2.36(q,J=8Hz,2H,ArCH2CH2),1.64(brs,4H,CH2CH2),1.24(s,6H,2×CH3),and 1.22(s,6H,2×CH3);13C NMR(75MHz,CDCl3)δ166.85(C=O),162.47(d,J1c,f=246Hz,4-ArC),144.74,142.54,142.07,140.11(d,J3c,f=9Hz,4-ArC),138.36,137.92,137.02,129.38(d,J3c,f=9Hz,4-ArC),126.45(d,J4c,f=3Hz,4-ArC),125.67,124.77,119.04,115.98(J2c,f=21Hz,4-ArC),113.85(J2c,f=21Hz,4-ArC),51.09(CO2CH3),35.15,35.09,34.15,33.94,31.87,31.83,and 31.10;IR(film)2960,2925,2860,1730(C=O),1610,1580,1490,1455,1435,1265,1195,1170,825,790,and 700cm-1;MS(DCI)m/e 421(MH+).
對(duì)于(2Z),(4Z)-4-苯基-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸甲酯(13j)量度=0.69mmol,產(chǎn)率=72%;
1H NMR(300MHz,CDCl3)δ7.19-7.30(m,3H,4-ArH),7.16(d,J=8Hz,1H,7-ArH),7.03-7.07(m,2H,4-ArH),7.00(d,J=2Hz,1H,7-ArH),6.84(dd,J=2,8Hz,1H,7-ArH),6.55(d,J=12Hz,1H,CH=CHCO2),6.00(t,J=8Hz,1H,C=CH),5.69(d,J=12Hz,1H,CH=CHCO2),3.19(s,3H,CO2CH3),2.62(t,J=8Hz,2H,ArCH2),2.36(q,J=8Hz,2H,ArCH2CH2),1.64(brs,4H,CH2CH2),1.24(s,6H,2×CH3),and 1.22(s,6H,2×CH3);13C NMR(75MHz,CDCl3)δ167.15(C=O),144.66,142.55,142.41,138.15,137.83,129.03,127.94,126.97,126.42,125.67,118.74,51.08(CO2CH3),35.27,35.16,35.10,34.15,33.94,31.89,31.84,and 30.04;IR(film)3020,2960,2825,2860,1730(C=O),1625,1495,1455,1435,1360,1275,1190,1170,825,765,and 700cm-1;MS(DCI)m/e 403(MH+),371(M+-OCH3).
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-7-[3-(1-金剛烷基)-4-甲氧苯基]-2,4-庚二烯酸甲酯(13k)量度=0.30mmol,產(chǎn)率=82%;
1H NMR(300MHz,CDCl3)δ7.49(m,1H,4-ArH),7.41(t,J=8Hz,1H,4-ArH),7.31(s,1H,4-ArH),7.23(m,1H,4-ArH),6.91(d,J=2Hz,1H,7-ArH),6.86(dd,J=2,8Hz,1H,7-ArH),6.74(d,J=8Hz,1H,7-ArH),6.55(dd,J=1,12Hz,1H,CH=CHCO2),6.07(brt,J=8Hz,1H,C=CH),5.73(d,J=12Hz,1H,CH=CHCO2),3.78(s,3H,OCH3),3.18(s,3H,CO2CH3),2.62(t,J=7Hz,2H,ArCH2),2.32(q,J=7Hz,2H,ArCH2CH2),2.04(s,9H,adamantyl),and 1.74(s,6H,adamantyl);13C NMR(75MHz,CDCl3)δ166.71(C=O),157.18,141.77,139.29,138.72,138.36,137.01,132.56,132.49,128.49,126.77,126.21,125.80,123.72(d,J3c,f=3Hz,4-ArC),123.70,119.17,111.63,55.03(ArOCH3),51.07(CO2CH3),40.55,and 37.12;IR(film)2905,2850,1730(C=O),1325,1235,1165,and 1125cm-1;MS(DCI)m/e 525(MH+),524(M+),523(M-H)+,135(C10H15+).Anal.Calcd for C32H35O3F3:C,73.26;H,6.72.Found:C,72.85;H,6.66.
對(duì)于(2Z),(4Z)-4-苯基-7-[3-(1-金剛烷基)-4-甲氧苯基]-2,4-庚二烯酸甲酯(13l)量度=0.86mmol,產(chǎn)率=51%;
1H NMR(300MHz,CDCl3)δ7.19-7.32(m,3H,4-ArH),7.07-7.10(m,2H,4-ArH),6.92(d,J=2Hz,1H,7-ArH),6.87(dd,J=2,8Hz,1H,7-ArH),6.74(d,J=8Hz,1H,7-ArH),6.55(dd,J=12,1Hz,1H,CH=CHCO2),5.99(t,J=8Hz,1H,C=CH),5.70(d,J=12Hz,1H,CH=CHCO2),3.78(s,3H,ArOCH3),3.19(s,3H,CO2CH3),2.62(t,J=7Hz,2H,ArCH2),2.37(q,J=7Hz,2H,ARCH2CH2),2.04(s,9H,adamantyl),and 1.75(s,6H,adamantyl);13C NMR(75MHz,CDCl3)δ167.14(C=O),157.11,142.57,138.33,138.12,137.96,137.87,132.92,129.06,127.96,126.95,126.75,126.23,118.71,111.59,55.08(OCH3),51.08(CO2CH3),40.57,37.14,36.87,35.06,31.34,and 29.11;IR(film)2905,2850,1730(C=O),1495,and 1235cm-1;MS(DCI)m/e 457(MH+),425(M-OCH3)+,255,135(C10H15+).Anal.Calcd for C31H36O3:C,81.54;H,7.95.Found:C,81.33;H,7.81.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-甲氧苯基]-2,4-庚二烯酸甲酯(13m)量度=0.46mmol,產(chǎn)率=96%;
1H NMR(300MHz,CDCl3)δ7.51(d,J=8Hz,1H,4-ArH),7.42(d,J=8Hz,1H,4-ArH),7.38(s,1H,4-ArH),7.21(d,J=8Hz,1H,4-ArH),7.08(d,J=8Hz,1H,7-ArH),6.64(d,J=8Hz,1H,7-ArH),6.56(m,2H,CH=CHCO2and 7-ArH),6.08(t,J=8Hz,1H,C=CH),5.74(d,J=12Hz,1H,CH=CHCO2),3.75(s,3H,OCH3),3.20(s,3H,CO2CH3),2.66(t,J=8Hz,2H,ArCH2),2.36(q,J=8Hz,2H,ArCH2CH2),2.06(s,9H,adamantyl),and 1.75(s,6H,adamantyl);13C NMR(75MHz,CDCl3)δ166.69(C=O),158.75,141.74,139.54,138.86,138.70,137.09,136.35,132.55,132.55,130.34(d,J2c,f=32Hz,4-ArC),128.54,126.41,125.80(d,J3c,f=4Hz,4-ArC),124.13(d,J1c,f=270Hz,CF3),123.77,120.24,119.35,111.88,54.86(OCH3),51.09(CO2CH3),40.65,37.14,36.68,35.08,30.98,and 29.12;IR(film)2905,2850,1730(C=O),1325,1250,1200,1165,1125,and 1070cm-1;MS(DCI)m/e 525(MH+),523(M-H+),135(C10H15+);Exact mass spectrum Calcd for C32H35O3F3Na(MNa+):547.2436.Found:547.2424.
對(duì)于(2Z),(4Z)-4-苯基-7-[4-(1-金剛烷基)-3-甲氧苯基]-2,4-庚二烯酸甲酯(13n)量度=2.95mmol,產(chǎn)率=96%;
1H NMR(300MHz,CDCl3)δ7.18-7.31(m,3H,4-ArH),7.04-7.08(m,3H,2×4-ArH and 1×7-ArH),6.63(dd,J=2,8Hz,1H,7-ArH),6.52-6.57(m,2H,1×7-ArH and CH=CHCO2),6.00(t,J=8Hz,1H,C=CH),5.69(d,J=12Hz,1H,CH=CHCO2),3.74(s,3H,OCH3),3.19(CO2CH3),2.63(t,J=8Hz,2H,ArCH2),2.38(q,J=8Hz,2H,ArCH2CH2),2.04(brs,9H,adamantyl),and 1.73(brs,6H,adamantyl);13C NMR(75MHz,CDCl3)δ167.13(C=O),158.69,142.50,139.92,138.23,137.80,137.58,136.18,129.05,127.95,126.99,126.28,120.23,118.81,111.95,54.90(OCH3),52.00(CO2CH3),40.65,37.14,36.65,35.19,30.90,and 29.10;IR(film)2905,2850,1730(C=O),1610,1495,1450,1435,1410,1250,1200,1170,1140,1040,1025,760,and 700cm-1;MS(DCI)m/e 457(MH+).
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-7-[2-(1-金剛烷基)-4-甲氧苯基]-2,4-庚二烯酸甲酯(13o)量度=0.31mmol,產(chǎn)率=80%;
1H NMR(300MHz,CDCl3)δ7.49(d,J=8Hz,1H,4-ArH),7.41(t,J=8Hz,1H,4-ArH),7.37(s,1H,4-ArH),7.31(d,J=7Hz,1H,4-ArH),6.92(d,J=8Hz,1H,7-ArH),6.82(d,J=3Hz,1H,7-ArH),6.62(dd,J=3,8Hz,1H,7-ArH),6.58(d,J=13Hz,1H,CH=CHCO2),6.11(t,J=8Hz,1H,C=CH),5.75(d,J=12Hz,1H,CH=CHCO2),3.74(s,3H,OCH3),3.20(s,3H,CO2CH3),2.92(m,2H,ArCH2),2.34(m,2H,ArCH2CH2),2.01(brs,3H,adamantyl),1.90(m,6H,adamantyl),and 1.71(m,6H,adamantyl);13C NMR(75MHz,CDCl3)δ166.68(C=O),157.58,149.01,141.68,138.98,138.67,136.95,132.62,131.74,128.53,125.69(d,J3c,f=4Hz,4-ArC),123.84(d,J3c,f=4Hz,4-ArC),119.44,113.08,109.94,55.07(OCH3),51.12(CO2CH3),42.07,37.84,36.74,33.19,32.90,and 29.08;IR(film)2910,2850,1730(C=O),1325,1165,and 1130 cm-1;MS(DCI)m/e 525(MH+),135(C10H15+).Anal.Calcd for C32H35O3F3·0.20 CH3CO2CH2CH3C,72.67;H,6.80.Found:C,72.65;H,6.68.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-5-[4-(1-金剛烷基)-3-甲氧苯基]-2,4-戊二烯酸甲酯(13p)量度=0.55mmol,產(chǎn)率=86%;
1H NMR(300MHz,CDCl3)δ7.41-7.55(m,4H,4-ArH),7.02(d,J=8Hz,1H,5-ArH),6.83(s,1H,C=CH),6.60-6.67(m,2H,CH=CHCO2and 5-ArH),6.25(d,J=2Hz,1H,5-ArH),5.83(d,J=12Hz,1H,CH=CHCO2),3.32(s,3H,OCH3),3.26(s,3H,CO2CH3),1.98(s,9H,adamantyl),and 1.71(s,6H,adamantyl);13C NMR(75MHz,CDCl3)δ166.74(C=O),158.21,142.10,139.42,139.13,136.35,135.84,133.80,133.38,130.95(d,J2c,f=32Hz,4-ArC),129.15,126.58(d,J3c,f=4Hz,4-ArC),126.36,124.13(d,J3c,f=4Hz,4-ArC),123.99(q,J1c,f=271Hz,CF3),122.96,120.08,112.03,54.23(ArOCH3),51.26(CO2CH3),40.36,37.03,36.96,and 28.98;IR(film)2905,2850,1730(C=O),1325,1255,1205,1165,and 1130 cm-1;MS(DCI)m/e 497(MH+),135(C10H15+).Anal.Calcd for C30H31O3F3:C,72.56;H,6.29.Found:C,72.43;H,6.32.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-叔丁基二甲基甲硅烷氧苯基]-2,4-庚二烯酸甲酯(13q)量度=1.29mmol,產(chǎn)率=79%;
1H NMR(300MHz,CDCl3)δ7.50(d,J=8Hz,1H,4-ArH),7.40(t,J=8Hz,1H,4-ArH),7.36(s,1H,4-ArH),7.22(d,J=8Hz,1H,4-ArH),7.07(d,J=8Hz,1H,7-ArH),6.61(dd,J=8,2Hz,1H,7-ArH),6.54(d,J=13Hz,HC=CHCO2),6.48(d,J=2Hz,1H,7-ArH),6.06(t,J=8Hz,1H,C=CH),5.73(d,J=12Hz,1H,HC=CHCO2),3.73(s,3H,ArOCH3),3.19(s,3H,CO2CH3),2.58(t,J=8Hz,2H,CH2Ar),2.31(q,J=7Hz,2H,ArCH2CH2),2.05(s,9H,adamantyl),1.73(s,6H,adamantyl),0.99(s,9H,t-butyl),and 0.26(s,6H,Si(CH3)2);13C NMR(75MHz,CDCl3)δ166.69(C=O),154.55,141.67,139.11,138.85,138.65,137.28,137.13,132.55,130.38(d,J2c,f=32Hz),130.16,128.53,126.97,125.75(d,J3c,f=4Hz),123.80(d,J3c,f=4Hz),120.33,119.30,119.05,51.10(CO2CH3),40.44,37.06,36.53,34.75,30.89,29.03,26.40,18.90(C(CH3)3),and-3.39(Si(CH3)2);IR(film)2930,2906,2854,1730(C=O),1324,1264,1254,1166,1128,856,and 836cm-1;MS(DCI)m/e 625(MH+),623(M-H)+,567(M-t-butyl)+,135(C10H15+).Anal.Calcd for C37H47O3F3:C,71.12;H,7.58.Found:C,70.80;H,7.30.
實(shí)施例13合成化合物14的一般方法將酯13的甲醇/四氫呋喃/2N氫氧化鈉溶液混合物(1∶1∶1,0.1M)加熱回流1-4h。然后冷卻至室溫,并加入10%鹽酸溶液,直至溶液達(dá)到PH1。用二氯甲烷萃取所得混濁混合物(2-4次),有機(jī)相用鹽水洗滌,于無水硫酸鎂上干燥,過濾,并濃縮。自戊烷中蒸發(fā)殘余物(3次),然后真空干燥。
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-5-(4-癸氧苯基)-2,4-戊二烯酸(14a)量度=0.49mmol,產(chǎn)率=100%,15∶1的2Z/2E異構(gòu)體混合物;
mp86-88℃;UVmax(CH3OH)300nm(ε=20,700),224nm(ε=10,900),324nm(ε=14,800);1H NMR(300MHz,CD3OD)δ7.41-7.57(m,4H,4-ArH),6.84-6.90(m,3H,2×5-ArH and C=CH),6.64-6.70(m,3H,2×5-ArH and CH=CHCO2),5.88(d,J=12Hz,1H,CH=CHCO2),3.89(t,J=6Hz,2H,ArOCH2),1.70(quint,J=6Hz,2H,ArOCH2CH2),1.28-1.50(m,14H,7×CH2),and 0.85(t,J=6Hz,3H,CH3);13C NMR(75MHz,CD3OD)δ169.90(C=O),160.40(5-ArC),143.42,141.17,136.29,135.98,134.69,132.11(5-ArC),129.49,127.69(q,J3c,f=4Hz,4-ArC),125.00(q,J3c,f=4Hz,4-ArC),121.90,115.17(5-ArC),68.97(ArOCH2),33.05,30.68,30.47,30.44,30.30,23.72,and 14.43;IR(KBr)2500-3500(br,CO2H),2955,2940,2920,2870,2850,1700(C=O),1600,1510,1470,1450,1420,1325,1310,1255,1180,and 1160cm-1;MS(DCI)m/e 475(MH+).Anal.Calcd for C28H33O3:C,70.87;H,7.01.Found:C,70.83;H,7.03.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-5-(3-癸氧苯基)-2,4-戊二烯酸(14b)量度=0.80mmol,產(chǎn)率=99%,18∶1的2Z/2E異構(gòu)體混合物。
UVmax(CH3OH)322nm(ε=19,000),234nm(ε=12,300);1H NMR(300MHz,CDCl3)δ7.56(d,J=7Hz,1H,4-ArH),7.41-7.51(m,3H,4-ArH),7.06(t,J=8Hz,1H,5-ArH),6.90(s,1H,C=CH),6.64-6.74(m,2H,5-ArH and CH=CHCO2),6.61(d,J=8Hz,1H,5-ArH),6.38(t,J=2Hz,1H,5-ArH),5.94(d,J=12Hz,1H,CH=CHCO2),3.56(t,J=7Hz,2H,ArOCH2),1.54-1.64(m,2H,ArOCH2CH2),1.21-1.35(m,14H,7×CH2),and 0.88(t,J=7Hz,3H,CH3);13C NMR(75MHz,CDCl3)δ169.95(C=O),160.10(5-ArC),142.97,140.95,138.38,135.78,134.66,130.34,130.20,127.78(q,J3c,f=4Hz,4-ArC),125.17(q,J3c,f=4Hz,4-ArC),123.49,122.87,116.19,115.38,68.66(ArOCH2),33.07,30.70,30.66,30.46,30.39,30.18,27.00,23.74,and 14.44;IR(film)2500-3400(br,CO2H),3060,2925,2855,1695(C=O),1600,1575,1490,1470,1435,1325,1265,1230,and 1165cm-1;MS(DCI)m/e 475(MH+).Anal.Calcd for C28H33O3F3:C,70.87;H,7.01.Found:C,70.68;H,6.99.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-5-(2-癸氧苯基)-2,4-戊二烯酸(14c)量度=0.61mmol,產(chǎn)率=100%,35∶1 2Z/2E異構(gòu)體混合物。
UVmax(CH3OH)320nm(ε=2,900),245nm(ε=3,000);1H NMR(300MHz,CD3OD)δ7.37-7.68(m,3H,4-ArH),7.23-7.30(m,1H,4-ArH),7.09-7.15(m,1H,5-ArH),7.07(brs,1H,C=CH),6.74-6.99(m,1H,5-ArH),6.72(dd,J=1,12Hz,1H,CH=CHCO2),6.62(dd,J=2,8Hz,1H,5-ArH),6.55(t,J=8Hz,1H,5-ArH),5.97(d,J=12Hz,1H,CH=CHCO2,2Z isomer),5.38(d,J=15Hz,1H,CH=CHCO2,2E isomer),3.97-4.05(m,2H,ArOCH2),1.73-1.87(m,2H,ArOCH2CH2),1.22-1.58(m,14H,7×CH2),and 0.86-0.89(m,3H,CH3);13C NMR(75MHz,CD3OD)δ169.80(C=O),158.72(5-ArC),143.43,141.02,137.68,134.48,132.10,131.51,131.44,131.15,130.93,130.32,129.94,127.57(q,J3c,f=4Hz,4-ArC),126.41,124.92(q,J3c,f=4Hz,4-ArC),123.07,122.14,120.77,113.43,112.94,69.45(ArOCH2),33.08,31.34,30.75,30.70,30.50,30.34,27.27,23.75,and 14.45;IR(film)2500-3500(br,CO2H),2925,2855,1695(C=O),1595,1455,1325,1290,1250,1165,and 1130cm-1;MS(DCI)m/e 475(MH+).Anal.Calcd for C28H33O3:C,70.87;H,7.01.Found:C,70.83;H,6.91.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-5-[4-(2E),(6E)-3,7-二甲基-辛-2,6-二烯-氧]苯基-2,4-戊二烯酸(14d)量度=0.74mmol,產(chǎn)率=98%;11∶1 2Z/2E異構(gòu)體混合物。
UVmax(CH3OH)324nm(ε=12,600),234nm(ε=9,200);1H NMR(300MHz,CD3OD)δ7.56(d,J=7Hz,1H,4-ArH),7.41-7.50(m,3H,4-ArH),6.84-6.88(m,3H,2×5-ArH and ArCH=C),6.65-6.70(m,3H,2×5-ArH and CH=CHCO2),5.88(d,J=12Hz,1H,CH=CHCO2),5.37(dt,J=1,7Hz,1H,C=CHCH2O),5.04-5.07(m,1H,CH=C(CH3)2),4.48(d,J=7Hz,2H,ArOCH2),2.04-2.11(m,4H,C=CHCH2CH2),and 1.58-1.69(m,9H,3×CH3);13C NMR(75MHz,CD3OD)δ170.15(C=O),160.10(5-ArC),143.43,141.93,141.15,136.33,135.98,134.70,132.58,132.07(5-ArC),130.33,129.56,127.68(q,J3c,f=4Hz,4-ArC),125.12(q,J3c,f=4Hz,4-ArC),124.94,121.88,121.03,115.49(5-ArC),65.81(ArOCH2),40.54,27.34,25.87,17.73,and 16.61;IR(KBr)2500-3500(br,CO2H),3035,2975,2930,2890,1700(C=O),1595,1510,1440,1420,1330,1310,1300,1255,1180,1135,and 1095cm-1;MS(DCI)m/e 471(MH+).Anal.Calcd for C28H29O3F3:C,71.47;H,6.21.Found:C,71.29;H,6.16.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-5-(3,4-雙癸氧苯基)-2,4-戊二烯酸/(2E),(4Z)-4-(3-三氟甲苯基)-5-(3,4-雙癸氧苯基)-2,4-戊二烯酸(14e)量度=1.09mmol,產(chǎn)率=73%,3∶2 2Z/2E異構(gòu)體混合物;
UVmax(CH3OH)350nm(sh,ε=21,200),242(ε=13,100);1H NMR(300MHz,CDCl3)δ7.36-7.72(m,4H,4-ArH),6.91(s,1H,C=CH from E-isomer),6.83(s,1H,C=CH from Z-isomer),6.59-6.71(m,3H,2×5-ArH and CH=CHCO2),6.31(d,J=2Hz,1H,5-ArH from Z-isomer),6.20(d,J=2Hz,1H,5-ArH from E-isomer),5.78(d,J=12Hz,1H,CH=CHCO2from Z-isomer),5.26(d,J=15Hz,1H,CH=CHCO2from E-isomer),3.89-3.94(m,2H,CH2OAr),3.43(t,J=7Hz,2H,CH2OAr from Z-isomer),3.36(t,J=7Hz,2H,CH2OAr from E-isomer),1.70-1.79(m,2H,CH2CH2OAr),1.51-1.63(m,2H,CH2CH2OAr),1.21-1.47(m,28H,14×CH2),and 0.83-0.88(m,6H,2×CH3);13C NMR(75MHz,CDCl3)δ171.80(C=O from E-isomer),166.81(C=O from Z-isomer),112.56-151.52(27 peaks from ArC and C=C,both isomers),68.99(CH2OAr),68.51(CH2OAr),68.31(CH2OAr),31.90,29.57,29.35,29.12,28.99,25.94,25.79,22.68,and 14.10;IR(KBr)2300-3300(br,CO2H),2955,2920,2850,1690(C=O from Z-isomer),1675(C=O from E-isomer),1615,1590,1510,1470,1430,1330,1275,1235,1205,1165,1140,1130,1070,and 1015cm-1;MS(FAB)m/e 630(M+).Anal.Calcd for C38H53O4F3:C,72.35;H,8.47.Found:C,72.45;H,8.48.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2,4-戊二烯酸(14f)量度=1.0,產(chǎn)率=100%;
UVmax(CH3OH)332nm(ε=23,800),282nm(ε=23,100),and 279nm(ε=22,800);1H NMR(300MHz,CD3OD)δ7.68(s,1H,ArH),7.58(s,1H,ArH),7.52(s,1H,ArH),7.42-7.47(m,2H,ArH),7.41(d,J=9Hz,1H,ArH),7.08(brs,1H,C=CH),6.80(dd,J=2,9Hz,1H,ArH),6.76(dd,J=1,12Hz,1H,CH=CHCO2),5.96(d,J=12Hz,1H,CH=CHCO2),1.76(s,4H,CH2CH2),and 1.35(brs,12H,4×CH3);13C NMR(75MHz,CD3OD/CDCl3)δ167.92(C=O),144.06,143.62,141.45,138.70,135.56,134.22,132.60,131.61,130.84,130.48,129.50,128.09,128.06,125.53,124.70,124.44,124.17,123.63,123.10,120.44,34.02(CH2CH2),33.46,33.36,and 30.86(4×CH3);IR(KBr)2400-3300(br,CO2H),3050,3010,2960,2930,2985,1695(C=O),1610,1430,1325,1310,1280,1250,1225,1180,and 1135cm-1;MS(DCI)m/e 479(MH+).Anal.Calcd for C30H29O2F3·0.25H2O:C,74.59;H,6.15.Found:C,74.56;H,6.14.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸(14g)量度=0.62mmol,產(chǎn)率=40%;
UVmax(CH3OH)252nm(ε=9,800);1H NMR(300MHz,CD3OD)δ7.51(brd,J=8Hz,1H,4-ArH),7.41(t,J=8Hz,1H,4-ArH),7.33(s,1H,4-ArH),7.16(d,J=8Hz,1H,7-ArH),7.13(d,J=8Hz,1H,4-ArH),6.99(d,J=2Hz,1H,7-ArH),6.79(dd,J=2,8Hz,1H,7-ArH),6.57(d,J=12Hz,1H,CH=CHCO2),6.08(t,J=8Hz,1H,C=CH),5.76(d,J=12Hz,1H,CH=CHCO2),2.62(t,J=8Hz,2H,ArCH2),2.27(q,J=8Hz,2H,ArCH2CH2),1.66(brs,4H,CH2CH2),1.24(s,6H,2×CH3),and 1.21(s,6H,2×CH3);13C NMR(75MHz,CD3OD)δ169.97(C=O),145.64,143.43,142.79,140.42,139.31,138.88,138.66,134.11,129.70,127.53(q,J3c,f=4Hz,4-ArC),126.92(q,J3c,f=4Hz,4-ArC),124.67,121.24,36.31,36.05,35.06,34.86,32.54,and 32.31;IR(film)2500-3500(br,CO2H),3020,2960,2930,2860,1700(C=O),1615,1455,1435,1355,1325,1310,1280,1250,1220,1165,1130,1100,1070,760,and 705cm-1;MS(DCI)m/e 457(MH+).Anal.Calcd for C28H31O2F3·0.15H2O:C,73.22;H,6.87.Found:C,73.25;H,6.90.
對(duì)于(2Z),(4Z)-4-(4-氟苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸(14h)量度=0.77mmol,產(chǎn)率=61%;
UVmax(CH3OH)252nm(ε=12,000);1H NMR(300MHz,CD3OD)δ7.16(d,J=8Hz,1H,7-ArH),6.99(d,J=2Hz,1H,7-ArH),6.91-6.97(m,4H,4-ArH),6.79(dd,J=2,8Hz,1H,7-ArH),6.50(d,J=12Hz,1H,CH=CHCO2),5.99(t,J=8Hz,1H,C=CH),5.72(d,J=12Hz,1H,CH=CHCO2),2.60(t,J=8Hz,2H,ArCH2),2.27(q,J=8Hz,2H,ArCH2CH2),1.67(brs,4H,CH2CH2),1.24(s,6H,2×CH3),and 1.22(s,6H,2×CH3);13C NMR(75MHz,CD3OD)δ170.43,163.23(d,J1c,f=246Hz,4-ArC),145.59,143.36,143.07,139.52,138.92,137.71,132.19(d,J3c,f=8Hz,4-ArC),127.62,127.47,126.95,120.84,115.54(d,J2c,f=21Hz,4-ArC),36.32,36.10,35.06,34.85,32.59,and 32.34;IR(film)2400-3500(br,CO2H),2960,2925,2860,1695(C=O),1605,1510,1455,1435,1360,1280,1220,1160,840,825,and 760cm-1;MS(DCI)m/e 407(MH+),389(M+-OH).Anal.Calcd for C27H31O2F:C,79.77;H,7.69.Found:C,79.40;H,7.51.
對(duì)于(2Z),(4Z)-4-(3-三氟苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸(14i)量度=1.13mmol,產(chǎn)率=74%;
UVmax(CH3OH)270nm(sh,ε=7,700),242(ε=9,700);1H NMR(300MHz,CDCl3)δ7.16-7.26(m,2H,1×4-ArH and 1×7-ArH),7.00(d,J=2Hz,1H,7-ArH),6.80-6.91(m,3H,2×4-ArH and 1×7-ArH),6.71(apparent dt,J=2,8Hz,1H,4-ArH),6.59(d,J=12Hz,1H,CH=CHCO2),6.03(t,J=8Hz,1H,C=CH),5.71(d,J=12Hz,1H,CH=CHCO2),2.62(t,J=8Hz,2H,ArCH2),2.37(q,J=8Hz,2H,ArCH2CH2),1.64(brs,4H,CH2CH2),1.23(s,6H,2×CH3),and 1.21(s,6H,2×CH3);13C NMR(75MHz,CDCl3)δ165.20(C=O),162.47(d,J1c,f=246Hz,4-ArC),145.14,144.74,142.52,140.01(d,J3c,f=8Hz,4-ArC),137.98,137.93,136.49,129.41(d,J3c,f=8Hz,4-ArC),126.45,125.71,124.77,115.97(d,J2c,f=21Hz,4-ArC),113.91(d,J2c,f=21Hz,4-ArC),35.14,35.09,34.14,33.94,31.87,31.83,and 31.19;IR(film)2400-3500(br,CO2H),2960,2925,2860,1700(C=O),1610,1580,1490,1455,1440,1360,1250,1220,1190,885,825,785,and 760cm-1;MS(DCI)m/e 407(MH+).Anal.Calcd for C27H31O2F:C,79.77;H,7.69.Found:C,79.21;H,7.76.
對(duì)于(2Z),(4Z)-4-苯基-7-(5,6,7,8-四氫-5,5,8,8-四甲基)-2-萘基)-2,4-庚二烯酸(14j)量度=0.45mmol,產(chǎn)率=81%;
UVmax(CH3OH)247nm(sh,ε=11,700),220(ε=19,000);1H NMR(300MHz,CD3OD)δ7.19-7.27(m,3H,4-ArH),7.15(d,J=8Hz,1H,7-ArH),6.95-7.00(m,3H,2×4-ArH and 1×7-ArH),6.80(dd,J=2,8Hz,1H,7-ArH),6.52(d,J=12Hz,1H,CH=CHCO2),5.99(t,J=8Hz,1H,C=CH),5.73(d,J=12Hz,1H,CH=CHCO2),2.60(t,J=8Hz,2H,ArCH2),2.29(q,J=8Hz,2H,ArCH2CH2),1.66(brs,4H,CH2CH2),1.24(s,6H,2×CH3),and 1.21(s,6H,2×CH3);13C NMR(75MHz,CD3OD)δ145.56,143.67,143.30,139.63,139.44,136.82,130.27,128.91,128.02,127.56,127.45,126.91,120.71,36.36,36.33,36.21,35.06,34.85,32.62,and 32.34;IR(film)2400-3500(br,CO2H),3020,2960,2925,2860,1695(C=O),1620,1495,1455,1440,1360,1285,1245,825,760,and 700cm-1;MS(DCI)m/e 389(MH+),371(M+-OH).Anal.Calcd for C27H32O2·0.2H2O:C,82.69;H,8.32.Found:C,82.76;H,8.27.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-7-[3-(1-金剛烷基)-4-甲氧苯基]-2,4-庚二烯酸(14k)量度=0.19mmol,產(chǎn)率=75%;
1H NMR(300MHz,CDCl3)δ7.46(d,J=8Hz,1H,4-ArH),7.37(d,J=8Hz,1H,4-ArH),7.32(m,1H,4-ArH),7.21(d,J=8Hz,1H,4-ArH),6.91(d,J=2Hz,1H,7-ArH),6.86(dd,J=2,8Hz,1H,7-ArH),6.73(d,J=8Hz,1H,7-ArH),6.63(d,J=12Hz,1H,CH=CHCO2),6.08(t,J=8Hz,1H,C=CH),5.72(d,J=12Hz,1H,CH=CHCO2),3.78(s,3H,OCH3),2.62(t,J=8Hz,2H,ArCH2),2.33(q,J=8Hz,2H,ArCH2CH2),2.04(s,9H,adamantyl),and 1.74(s,6H,adamantyl);13C NMR(75MHz,CDCl3)δ170.89(C=O),157.17,145.10,138.98,138.66,138.36,136.50,132.48,130.35(d,J2c,f=32Hz,4-ArC),128.43,126.77,126.24,125.75(d,J3c,f=4Hz,4-ArC),124.47,123.79(d,J3c,f=4Hz,4-ArC),120.48(d,J1c,f=271Hz,CF3),118.41,111.63,55.03(OCH3),40.56,37.13,36.86,34.77,31.50,and 29.10;IR(film)2400-3500(br,CO2H),2905,2850,1700(C=O),1325,1235,1165,and 1130cm-1;MS(DCI)m/e 511(MH+),135(C10H15+).Anal.Calcd for C31H33O3F3:C,72.92;H,6.51.Found:C,72.93;H,6.58.
對(duì)于(2Z),(4Z)-4-苯基-7-[3-(1-金剛烷基)-4-甲氧苯基]-2,4-庚二烯酸(14l)量度=0.37mmol,產(chǎn)率=60%;
1H NMR(300MHz,CDCl3)δ7.19-7.33(m,3H,4-ArH),7.12(m,2H,4-ArH),6.95(d,J=2Hz,1H,7-ArH),6.90(d,J=8Hz,1H,7-ArH),6.75(d,J=8Hz,1H,7-ArH),6.66(d,J=12Hz,1H,CH=CHCO2),6.03(t,J=8Hz,1H,C=CH),5.72(d,J=12Hz,1H,CH=CHCO2),3.79(s,3H,ArOCH3),2.64(t,J=7Hz,2H,ArCH2),2.41(q,J=7Hz,2H,ArCH2CH2),2.07(s,9H,adamantyl),and 1.77(s,6H,adamantyl);13C NMR(75MHz,CDCl3)δ171.65(C=O),157.12,145.98,138.33,137.85,137.44,137.15,133.01,128.02,127.08,126.79,126.31,118.19,111.62,55.10(OCH3),40.60,37.17,36.90,34.93,31.49,and 29.14;IR(KBr)2400-3600(br,CO2H),2905,2850,1695(C=O),1495,1445,1235,and 700cm-1;MS(DCI)m/e 443(MH+),255,135(C10H15+).Anal.Calcd for C30H34O3·0.11H2O:C,81.05;H,7.76.Found:C,80.68;H,7.78.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-甲氧苯基]-2,4-庚二烯酸(14m)量度=0.75mmol,產(chǎn)率=77%;
1H NMR(300MHz,CDCl3)δ7.46(d,J=8Hz,1H,4-ArH),7.35(m,2H,4-ArH),7.17(d,J=8Hz,1H,4-ArH),7.07(d,J=8Hz,1H,7-ArH),6.60-6.60(m,2H,7-ArH and CH=CHCO2),6.55(d,J=2Hz,1H,7-ArH),6.08(t,J=7Hz,1H,C=CH),5.72(d,J=12Hz,1H,CH=CHCO2),3.74(s,3H,OCH3),2.64(t,J=7Hz,2H,ArCH2),2.36(q,J=7Hz,2H,ArCH2CH2),2.05(s,9H,adamantyl),and 1.74(s,6H,adamantyl);13C NMR(75MHz,CDCl3)δ170.95(C=O),158.74,145.01,139.59,138.63,138.54,136.56,136.35,132.46,130.36(d,J2c,f=32Hz,4-ArC),128.47,126.39,125.78(d,J3c,f=4Hz,4-ArC),123.84(d,J3c,f=4Hz,4-ArC),122.28,120.25,118.59,111.92,54.87(OCH3),40.64,37.14,36.67,34.92,31.06,and 29.10;IR(KBr)2400-3600(br,CO2H),2905,2850,1700(C=O),1325,1250,1165,and 1130cm-1;MS(DCI)m/e 511(MH+),135(C10H15+).Anal.Calcd for C31H33O3F3:C,72.92;H,6.51.Found:C,72.90;H,6.65.
對(duì)于(2Z),(4Z)-4-苯基-7-[4-(1-金剛烷基)-3-甲氧苯基]-2,4-庚二烯酸(14n)量度=1.93mmol,產(chǎn)率=65%;
UVmax(CH3OH)284nm(sh,ε=8,000),276(ε=9,200),242(ε=14,500);1H NMR(300MHz,CDCl3)δ7.17-7.29(m,3H,4-ArH),7.04-7.08(m,3H,2×4-ArH and 1×7-ArH),6.60-6.65(m,2H,1×7-ArH and CH=CHCO2),6.56(d,J=2Hz,1H,7-ArH),6.01(t,J=8Hz,1H,C=CH),5.71(d,J=12Hz,1H,CH=CHCO2),3.73(s,3H,OCH3),2.63(t,J=8Hz,2H,ArCH2),2.41(q,J=8Hz,2H,ArCH2CH2),2.04(brs,9H,adamantyl),and 1.74(brs,6H,adamantyl);13C NMR(75MHz,CDCl3)δ170.48(C=O),158.71,145.81,139.97,137.76,137.58,136.69,136.20,129.03,127.99,127.11,126.28,120.31,118.07,112.06,54.92(OCH3),40.68,37.15,36.66,35.02,30.98,and 29.12;IR(KBr)2400-3600(br,CO2H);3055,3030,2905,2850,1695(C=O),1610,1570,1495,1450,1410,1290,1245,1180,1160,1140,1040,1025,810,and 700cm-1;MS(DCI)m/e 443(MH+).Anal.Calcd for C30H34O3:C,81.41;H,7.74.Found:C,81.03;H,7.78.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-7-[2-(1-金剛烷基)-4-甲氧苯基]-2,4-庚二烯酸(14o)量度=0.21mmol,產(chǎn)率=77%;
1H NMR(300MHz,CDCl3)δ7.45(m,1H,4-ArH),7.36(m,2H,4-ArH),7.28(d,J=8Hz,1H,4-ArH),6.92(d,J=8Hz,1H,7-ArH),6.92(d,J=3Hz,1H,7-ArH),6.82(d,J=3Hz,1H,7-ArH),6.60-6.67(m,2H,7-ArH and CH=CHCO2),6.12(t,J=8Hz,1H,C=CH),5.74(d,J=12Hz,1H,CH=CHCO2),3.74(s,3H,OCH3),2.90(m,2H,ArCH2),2.35(m,2H,ArCH2CH2),1.89-2.08(s,9H,adamantyl),and 1.62-1.75(m,6H,adamantyl);13C NMR(75MHz,CDCl3)δ170.74(C=O),157.57,149.02,145.04,138.58,136.42,132.65,132.53,131.79,130.22,128.47,125.67(d,J3c,f=4Hz,4-ArC),123.91(d,J3c,f=3Hz,4-ArC),118.63,113.08,109.93,55.07(OCH3),42.18,42.05,37.83,36.74,32.99,and 29.07;IR(KBr)2400-3600(br,CO2H),2905,2850,1700(C=O),1610,1325,1250,1165,and 1125cm-1;MS(DCI)m/e 511(MH+),135(C10H15+).Anal.Calcd for C31H33O3F3:C,72.92;H,6.51.Found:C,72.55;H,6.47.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-5-[4-(1-金剛烷基)-3-甲氧苯基]-2,4-戊二烯酸(14p)量度=0.37mmol,產(chǎn)率=84%;
1H NMR(300MHz,CDCl3)δ7.50(s,1H,4-ArH),7.34-7.46(m,3H,4-ArH),7.03(d,J=8Hz,1H,5-ArH),6.84(s,1H,C=CH),6.70(dd,J=1,12Hz,1H,CH=CHCO2),6.64(dd,J=2,8Hz,1H,5-ArH),6.30(d,J=2Hz,1H,5-ArH),5.80(d,J=12Hz,1H,CH=CHCO2),3.32(s,3H,OCH3),1.98(s,9H,adamantyl),and 1.71(s,6H,adamantyl);13C NMR(75MHz,CDCl3)δ171.15(C=O),158.21,145.28,139.42,139.24,136.25,135.48,133.80,133.22,130.95(d,J2c,f=32Hz,4-ArC),129.09,126.47(d,J3c,f=3Hz,4-ArC),126.37,124.21(d,J3c,f=3Hz,4-ArC),123.06,120.42(q,J1c,f=271Hz,CF3),112.16,54.22(OCH3),40.36,37.04,36.98,and 28.98;IR(KBr)2400-3600(br,CO2H),2910,2880,2850,1690(C=O),1330,1250,1240,1165,and 1120cm-1;MS(DCI)m/e 483(MH+),135(C10H15+).Anal.Calcd for C29H29O3F3:C,72.18;H,6.06.Found:C,72.19;H,6.09.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-羥苯基]-2,4-庚二烯酸(14q)利用上述一般方法(實(shí)施例12)制備。粗產(chǎn)物經(jīng)柱層析純化(20∶1硅膠/粗產(chǎn)物;用5%甲醇/二氯甲烷洗脫),量度=0.33mmol,產(chǎn)率=55%;
1H NMR(300MHz,CDCl3)δ7.48(d,J=8Hz,1H,4-ArH),7.35-7.39(m,2H,4-ArH),7.19(d,J=8Hz,1H,4-ArH),7.06(d,J=8Hz,1H,7-ArH),6.59-6.65(m,2H,CH=CHCO2and 7-ArH),6.34(d,J=2Hz,1H,7-ArH),6.04(t,J=7Hz,1H,C=CH),5.75(d,J=12Hz,1H,HC=CHCO2),2.58(t,J=7Hz,2H,CH2Ar),2.34(q,J=7Hz,2H,ArCH2CH2),2.04-2.07(m,9H,adamantyl),and 1.74(s,6H,adamantyl);13C NMR(75MHz,CDCl3)δ171.18(C=O),154.28,145.48,139.66,138.58,137.84,136.34,134.21,132.46,130.43(d,J2c,f=32Hz,4-ArC),128.58,126.95,125.69(d,J3c,f=4Hz,4-ArC),124.07(d,J1c,f=271Hz,CF3),123.96(d,J2c,f=3Hz,4-ArC),120.58,118.51,116.97,40.59,37.05,36.38,34.27,30.82,and 29.02;IR(KBr)2500-3600(br,CO2H),2905,2850,1680(C=O),1615,1420,1325,1270,1260,1225,1165,1125,and 1075cm-1;MS(DCI)m/e 497(MH+),496(M+),495(M-H)+,135(C10H15+).Anal.Calcd for C30H31O3F3:C,72.56;H,6.29.Found:C,72.56;H,6.37.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-戊氧苯基]-2,4-庚二烯酸(14r)由16r制得;通過柱層析純化(40∶1硅膠/粗產(chǎn)物;用3%甲醇/二氯甲烷洗脫);量度=0.55mmol,產(chǎn)率=74%;
1H NMR(300MHz,CDCl3)δ7.45(d,J=7Hz,1H,4-ArH),7.33-7.38(m,2H,4-ArH),7.17(d,J=8Hz,1H,4-ArH),7.06(d,J=8Hz,1H,7-ArH),6.57-6.65(m,2H,7-ArH and HC=CHCO2),6.54(d,J=2Hz,1H,7-ArH),6.08(t,J=8Hz,1H,C=CH),5.73(d,J=12Hz,1H,HC=CHCO2),3.86(t,J=6.5Hz,2H,OCH2),2.63(t,J=8Hz,2H,CH2Ar),2.36(q,J=8Hz,2H,ArCH2CH2),2.04-2.07(m,9H,adamantyl),1.83(quint,J=7Hz,2H,OCH2CH2),1.74(s,6H,adamantyl),1.45-1.56(m,2H,O(CH2)2CH2),1.33-1.42(m,2H,O(CH2)3CH2),and 0.93(t,J=7Hz,3H,O(CH2)4CH3);13C NMR(75MHz,CDCl3)δ170.84(C=O),158.09,145.00,139.49,138.73,138.61,136.57,136.04,132.48,130.36(d,J2c,f=32Hz,4-ArC),128.46,126.35,125.76,123.80,119.92,119.59,118.49,112.08,67.52(OCH2),40.59,37.17,36.70,35.12,31.09,30.27,29.12,28.65,22.43,and 14.08;IR(film)2400-3300(br,CO2H),2905,2850,1700(C=O),1325,1165,and 1130cm-1;MS(DCI)m/e 567(MH+),549(M-OH)+,431(M-C10H15)+,135(C10H15+).Anal.Calcd for C35H41O3F3:C,74.18;H,7.29.Found:C,73.99;H,7.39.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-(3,5-二氟芐氧基)苯基]-2,4-庚二烯酸(14s)由16s制得,通過柱層析純化(20∶1硅膠/粗產(chǎn)物,用3%甲醇/二氯甲烷洗脫);量度=0.48mmol,產(chǎn)率=86%;
1H NMR(300MHz,CDCl3)δ7.46(d,J=8Hz,1H,4-ArH),7.32-7.38(m,2H,4-ArH),7.17(d,J=8Hz,1H,4-ArH),7.13(d,J=8Hz,1H,7-ArH),7.00(d,J=6Hz,2H,HArCH2),6.67-6.78(m,2H,HArCH2and 7-ArH),6.62(d,J=13Hz,1H,HC=CHCO2),6.56(d,J=1.5Hz,1H,7-ArH),6.05(t,J=8Hz,1H,C=CH),5.73(d,J=12Hz,1H,HC=CHCO2),4.98(s,2H,OCH2),2.63(t,J=8Hz,2H,CH2Ar),2.35(q,J=8Hz,2H,ArCH2CH2),2.04-2.08(m,9H,adamantyl),and 1.72(s,6H,adamantyl);13C NMR(75MHz,CDCl3)δ170.71(C=O),163.22(d,J1c,f=247Hz,3,5-difluorobenzyl),157.23,145.02,139.73,138.58,138.34,136.64,136.47,132.43,128.49,126.88,125.76,123.89,121.08,118.57,112.79,109.68(d,J2c,f=25Hz,3,5-difluorobenzyl),102.98(t,J2c,f=25Hz,3,5-difluorobenzyl),68.89(CH2O),40.68,37.04,36.77,34.85,31.02,and 29.02;IR(KBr)2400-3600(br,CO2H),2905,2850,1700(C=O),1630,1600,1325,1245,1165,1120,1070cm-1;MS(DCI)m/e 623(MH+),622(M+),621(M-H)+,135(C10H15+).Anal.Calcd for C37H35O3F5:C,71.37;H,5.67.Found:C,70.93;H,5.62.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-(4-甲氧芐氧基)苯基]-2,4-庚二烯酸(14t)由16t制得,經(jīng)柱層析純化(20∶1硅膠/粗產(chǎn)物,用3%甲醇/二氯甲烷洗脫);量度=0.55mmol,產(chǎn)率=73%;
1H NMR(300MHz,CDCl3)δ7.46(d,J=8Hz,1H,4-ArH),7.32-7.40(m,4H,2×4-ArH and 2×HArCH2),7.17(d,J=7.5Hz,1H,4-ArH),7.10(d,J=8Hz,1H,7-ArH),6.91(dt,J=9,2Hz,2H,HArCH2),6.59-6.66(m,3H,2×7-ArH and HC=CHCO2),6.06(t,J=7Hz,1H,C=CH),5.73(d,J=12Hz,1H,HC=CHCO2),4.93(s,2H,OCH2),3.82(s,3H,OCH3),2.64(t,J=8Hz,2H,CH2Ar),2.36(q,J=8Hz,2H,ArCH2CH2),2.07-2.08(m,6H,adamantyl),1.99(s,3H,adamantyl),and 1.68(s,6H,adamantyl);13C NMR(75MHz,CDCl3)δ170.60(C=O),159.14,157.80,144.99,139.57,138.61,138.56,136.59,136.39,132.47,130.57,130.14,129.71,129.46,128.88,128.48,126.57,125.79(d,J3c,f=4Hz,4-ArC),123.85(d,J3c,f=4Hz,4-ArC),122.29,120.44,118.50,113.81,112.75,69.73(OCH2),55.29(OCH3),40.56,37.08,36.73,34.91,31.04,and 29.06;IR(KBr)2500-3600(br,CO2H),2905,2850,1700(C=O),1610,1515,1325,1245,1165,1130,1070,1030,and 805cm-1;MS(DCI)m/e 617(MH+),616(M+),615(M-H)+,135(C10H15+),121.Anal.Calcd for C38H39O4F3:C,74.01;H,6.37.Found:C,73.77;H,6.35.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-芐氧苯基]-2,4-庚二烯酸(14u)由16u制得;經(jīng)柱層析純化(20∶1硅膠/粗產(chǎn)物;用3%甲醇/二氯甲烷洗脫),量度=0.47mmol,產(chǎn)率=98%;
1H NMR(300MHz,CDCl3)δ7.31-7.48(m,8H,5×HArCH2and 3×4-ArH),7.17(d,J=8Hz,1H,4-ArH),7.12(d,J=8Hz,1H,7-ArH),6.60-6.67(m,3H,2×7-ArH and HC=CHCO2),5.01(s,2H,OCH2),2.64(t,J=8Hz,2H,CH2Ar),2.36(q,J=8Hz,2H,ArCH2CH2),2.01-2.10(m,9H,adamantyl),and 1.70(s,6H,adamantyl);13C NMR(75MHz,CDCl3)δ170.86(C=O),157.74,145.07,139.62,138.61,137.40,136.60,136.42,130.37(d,J2c,f=32Hz,4-ArC),132.46,128.46,127.65,127.25,126.63,125.82,123.83,120.55,118.50,112.76,70.00(OCH2),40.58,37.07,36.75,34.91,31.05,and 29.06;IR(KBr)2400-3600(CO2H),2905,2850,1700(C=O),1325,1245,1165,and 1130cm-1;MS(DCI)m/e 587(MH+),135(C10H15+),91(C7H7+).Anal.Calcd for C37H37O3F3:C,75.75;H,6.36.Found:C,75.58;H,6.53.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-(羧基苯氧基)苯基]-2,4-庚二烯酸(14v)除回流時(shí)間增至48h后,其余按一般方法,由(2Z),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-叔丁氧羰基甲氧基)-苯基]-2,4-庚二烯酸甲酯(14v)制得,量度=0.16mmol,產(chǎn)率=90%;
1H NMR(300MHz,CDCl3)δ10.19(brs,2H,CO2H),7.46(d,J=8Hz,1H,4-ArH),7.32-7.37(m,2H,4-ArH),7.11-7.15(m,2H,4-ArH and 7-ArH),6.70(d,J=8Hz,1H,7-ArH),6.64(d,J=12Hz,1H,HC=CHCO2),6.43(s,1H,7-ArH),6.07(t,J=7Hz,1H,C=CH),5.75(d,J=12Hz,1H,HC=CHCO2),4.58(s,2H,OCH2),2.64(t,J=7Hz,2H,ArCH2),2.37(q,J=7Hz,2H,ArCH2CH2),2.04-2.08(m,9H,adamantyl),and 1.75(s,6H,adamantyl);13C NMR(75MHz,CDCl3)δ174.87(C=O),171.77(C=O),156.53,145.33,139.61,138.51,138.29,136.77,136.54,132.47,130.41(d,J2c,f=32Hz,4-ArC),128.56,127.04,125.70,123.90,122.25,121.53,118.49,112.49,64.77(OCH2),40.60,37.01,36.74,34.63,30.88,and 29.08;IR(KBr)2400-3600(br,CO2H),2905,2850,1730(C=O),1705(C=O),1435,1420,1325,1245,1165,1130,and 1070cm-1;MS(DCI)m/e 555(MH+),135(C10H15+).Anal.Calcd for C32H33F3O5:C,69.30;H,6.00.Found:C,69.12;H,5.98.
實(shí)施例14合成(2Z),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-羥苯基]-2,4-庚二烯酸甲酯(15)的方法通過滴加1.1M氟化四丁銨(3.64ml,4.00mmol),處理13q(2.50g,4.00mmol)的THF(100ml)無色溶液。5min后,將黃色反應(yīng)混合物在乙醚和飽和氯化銨溶液之間分配。有機(jī)相用鹽水洗滌,用無水硫酸鎂干燥,過濾,并濃縮。殘余物通過柱層析純化(40∶1硅膠/粗產(chǎn)物;依次用己烷和2∶1二氯甲烷/己烷洗脫),得到1.99g黃色油狀物。將其溶于戊烷(150ml),并冷卻至-30℃。過濾收集在18h內(nèi)形成的沉淀物,真空干燥,得到1.57g(77%)化合物15黃色固體;
1H NMR(300MHz,CDCl3)δ7.52(d,J=8Hz,1H,4-ArH),7.42(t,J=8Hz,1H,4-ArH),7.38(s,1H,4-ArH),7.24(d,J=8Hz,1H,4-ArH),7.08(d,J=8Hz,1H,7-ArH),6.62(dd,J=8,2Hz,1H,7-ArH),6.57(d,J=12Hz,HC=CHCO2),6.41(d,J=2Hz,1H,7-ArH),6.03(t,J=8Hz,1H,C=CH),5.77(d,J=12Hz,1H,HC=CHCO2),4.95(s,1H,OH),3.27(s,3H,CO2CH3),2.62(t,J=7Hz,2H,CH2Ar),2.35(q,J=7Hz,2H,ArCH2CH2),2.06-2.09(m,9H,adamantyl),and 1.77(s,6H,adamantyl);13C NMR(75MHz,CDCl3)δ166.86(C=O),154.38,142.16,139.60,138.63,138.21,136.93,134.21,132.52,130.34(d,J2c,f=32Hz,4-ArC),128.59,126.89,125.73(d,J3c,f=4Hz,4-ArC),123.84(d,J3c,f=4Hz,4-ArC),120.55,119.38,116.81,51.25(CO2CH3),40.59,37.05,36.37,34.36,30.58,and 29.01;IR(KBr)3385(OH),2905,2850,1700(C=O),1325,1315,1230,1155,1125,1075cm-1;MS(DCI)m/e 511(MH+),509(M-H)+,135(C10H15+).Anal.Calcd for C31H33O3F3·C5H12:C,73.60;H,7.19.Found:C,73.62;H,7.04.
實(shí)施例15合成化合物16的一般方法方法A用烷基鹵(1-2當(dāng)量)、碘化鉀(0-0.1當(dāng)量)和粉狀無水碳酸鉀(1當(dāng)量)處理苯酚15(1當(dāng)量)的丙酮溶液(0.2-0.3M)。攪拌不均勻反應(yīng)混合物,并加熱回流24h。緩慢冷卻所得淤漿,然后減壓除去丙酮。殘余物在乙醚和水之間分配。有機(jī)相用鹽水洗滌,于無水硫酸鎂上干燥,過濾,濃縮。粗產(chǎn)物通過柱層析純化(20∶1-40∶1硅膠/粗產(chǎn)物;用5%乙酸乙酯/己烷洗脫)。
方法B在氮?dú)猸h(huán)境下用氫化鈉(60%分散于油,0.98當(dāng)量)處理酚15(1當(dāng)量)和烷基鹵(1-1.5當(dāng)量)的二甲基甲酰胺溶液(約0.12M)。攪拌反應(yīng)混合物1-18h,并在水和2∶1己烷/乙酸乙酯間分配。水洗(5x)有機(jī)相,于無水硫酸鎂上干燥,過濾,濃縮。通過柱層析純化粗產(chǎn)物(20∶1-40∶1硅膠/粗產(chǎn)物;用5-10%乙酸乙酯/己烷洗脫)。
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-戊氧苯基]-2,4-庚二烯酸甲酯(16r)采用方法B,利用戊基碘,量度=0.59mmol,產(chǎn)率=58%;
1H NMR(300MHz,CDCl3)δ7.51(d,J=8Hz,1H,4-ArH),7.39-7.44(m,2H,4-ArH),7.21(d,J=8Hz,1H,4-ArH),7.09(d,J=8Hz,1H,7-ArH),6.63(d,J=8Hz,1H,7-ArH),6.55-6.59(m,7-ArH and HC=CHCO2),6.09(t,J=8Hz,1H,C=CH),5.75(d,J=12Hz,1H,HC=CHCO2),3.89(t,J=6.5Hz,2H,OCH2),3.21(s,3H,CO2CH3),2.66(t,J=8Hz,2H,CH2Ar),2.37(q,J=8Hz,2H,ArCH2CH2),2.06-2.10(m,9H,adamantyl),1.76-1.90(m,8H,OCH2CH2and 6×adamantyl),1.54(quint,J=7Hz,2H,O(CH2)2CH2),1.43(quint,J=7Hz,2H,O(CH2)3CH2),and 0.96(t,J=7Hz,3H,O(CH2)4CH3);13C NMR(75MHz,CDCl3)δ166.71(C=O),158.13,141.76,139.45,138.97,138.72,137.08,136.06,132.57,130.34(d,J2c,f=32Hz,4-ArC),128.55,126.38,125.82(d,J3c,f=4Hz,4-ArC),123.75(d,J3c,f=4Hz,4-ArC),120.63(d,J1c,f=257Hz,CF3),119.92,119.31,112.07,67.52(OCH2),51.10(CO2CH3),40.64,37.20,36.73,35.12,31.02,29.20,29.16,28.68,22.45,and 14.10;IR(film)2905,2850,1730(C=O),1325,1165,and 1125cm-1;MS(DCI)m/e 581(MH+),549(M-OCH3)+,445(M-C10H15)+,135(C10H15+).Anal.Calcd for C36H43O3F3:C,74.46;H,7.46.Found:C,74.40;H,7.33.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-(3,5-二氟芐氧基)苯基]-2,4-庚二烯酸甲酯(16s)利用方法B,使用3,5-二氟芐基溴,量度=0.65mmol,產(chǎn)率=82%;
1H NMR(300MHz,CDCl3)δ7.49(d,J=8Hz,1H,4-ArH),7.40(t,J=8Hz,1H,4-ArH),7.35(s,1H,4-ArH),7.19(d,J=8Hz,1H,4-ArH),7.13(d,J=8Hz,1H,7-ArH),6.97-7.00(m,2H,HArCH2),6.75(tt,J=9,2Hz,1H,HArCH2),6.69(dd,J=8,2Hz,1H,7-ArH),6.52-6.56(m,2H,7-ArH and HC=CHCO2),6.05(t,J=7.5Hz,1H,C=CH),5.74(d,J=12Hz,1H,HC=CHCO2),4.99(s,2H,OCH2Ar),3.19(s,3H,OCH3),2.64(t,J=8Hz,2H,CH2Ar),2.33(q,J=8Hz,2H,ArCH2CH2),2.04-2.09(m,9H,adamantyl),and 1.72(s,6H,adamantyl);13C NMR(75MHz,CDCl3)δ166.67(C=O),168.33(d,J1c,f=248Hz,3,5-difluorobenzyl),157.23,141.69,141.49,139.69,138.64,138.59,137.13,136.47,132.50,128.55,126.88,125.79(d,J3c,f=4Hz,4-ArC),123.81(d,J3c,f=4Hz,4-ArC),121.06,119.42,112.78,109.60,119.66(d,J2c,f=25Hz,3,5-difluorobenzyl),102.99(t,J2c,f=25Hz,3,5-difluorobenzyl),68.88(CH2O),51.12(OCH3),40.68,37.03,36.77,35.01,30.94,and 29.01;IR(film)2905,2850,1725(C=O),1600,1325,1165,1120,and 1070cm-1;MS(DCI)m/e 637(MH+),636(M+),635(M-H)+,605(M-OCH3)+,135(C10H15+).Anal.Calcd for C38H37O3F5:C,71.69;H,5.86.Found:C,71.53;H,5.82.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-(4-甲氧芐氧基)苯基]-2,4-庚二烯酸甲酯(16t)采用方法A,利用4-甲氧芐基氯,量度=0.65mmol,產(chǎn)率=84%;
1H NMR(300MHz,CDCl3)δ7.52(d,J=8Hz,1H,4-ArH),7.38-7.45(m,4H,2×4-ArH and 2×HArCH2),7.21(d,J=7.5Hz,1H,4-ArH),7.11(d,J=8Hz,1H,7-ArH),6.93(d,J=9Hz,2H,HArCH2),6.65-6.69(m,2H,2×7-ArH),6.56(d,J=12Hz,1H,HC=CHCO2),6.09(t,J=7Hz,1H,C=CH),5.67(d,J=12Hz,1H,HC=CHCO2),4.94(s,2H,OCH2),3.83(s,3H,ArOCH3),3.20(s,3H,CO2CH3),2.67(t,J=8Hz,2H,CH2Ar),2.38(q,J=8Hz,2H,ArCH2CH2),2.09(s,6H,adamantyl),2.01(s,3H,adamantyl),and 1.60(s,6H,adamantyl).
對(duì)于(2Z),(4Z)-2-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-芐氧苯基]-2,4-庚二烯酸甲酯(16u)采用方法A,利用芐基溴,量度=0.59mmol,產(chǎn)率=92%;采用方法B,量度=0.08mmol,產(chǎn)率=79%;
1H NMR(300MHz,CDCl3)δ7.30-7.52(m,8H,5×HArCH2and 3×4-ArH),7.20(d,J=8Hz,1H,4-ArH),7.13(d,J=8Hz,1H,7-ArH),6.66-6.68(m,2H,2×7-ArH),6.55(d,J=13Hz,1H,HC=CHCO2),6.07(t,J=7Hz,1H,C=CH),5.75(d,J=12Hz,1H,HC=CHCO2),5.03(s,2H,OCH2),3.19(s,3H,OCH3),2.66(t,J=8Hz,2H,CH2Ar),2.35(q,J=8Hz,2H,ArCH2CH2),2.02-2.11(m,9H,adamantyl),and 1.71(s,6H,adamantyl);IR(film)2905,2850,1700(C=O),1325,1245,1165,1130,1070,1025,805,and 695cm-1;MS(DCI) m/e 601(MH+),600(M+),599(M-H)+,509(M-CH2Ph)+,135(C10H15+).
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-(丁氧羰基甲氧基)苯基]-2,4-庚二烯酸甲酯(16v)采用方法B由溴代乙酸叔丁酯制得,量度=1.30mmol,產(chǎn)率=62%。
1H NMR(300MHz,CDCl3)δ7.51(d,J=8Hz,1H,4-ArH),7.42(t,J=8Hz,1H,4-ArH),7.37(s,1H,4-ArH),7.22(d,J=8Hz,1H,4-ArH),7.11(d,J=8Hz,1H,7-ArH),6.68(dd,J=8,2Hz,1H,7-ArH),6.57(d,J=12Hz,1H,HC=CHCO2),6.41(d,J=2Hz,1H,7-ArH),6.07(t,J=7Hz,1H,C=CH),5.77(d,J=12Hz,1H,HC=CHCO2),4.43(s,2H,OCH2),3.20(s,3H,OCH3),2.63(t,J=7Hz,2H,ArCH2),2.35(q,J=7Hz,2H,ArCH2CH2),2.06-2.11(m,9H,adamantyl),1.72-1.82(m,6H,adamantyl),and 1.48(s,9H,t-butyl).
實(shí)施例16合成化合物17的一般方法于室溫及氬氣條件下依次用二乙基膦酰乙酸甲酯(1.5當(dāng)量)和甲醇鈉(25wt%于甲醇,1.4當(dāng)量)處理醛9(1當(dāng)量)的無水甲苯溶液(0.1M)。于室溫下攪拌該反應(yīng)混合物12-16h,再加入甲醇鈉(25wt%于甲醇,1當(dāng)量)處理。攪拌混合物0.5h,然后在乙醚和飽和氯化銨溶液之間分散,有機(jī)相用飽和氯化鈉溶液洗滌,于無水硫酸鎂上干燥,過濾,并濃縮。通過柱層析純化(40∶1硅膠/粗產(chǎn)物;用5%乙酸乙酯的己烷洗脫),得到所需產(chǎn)物。
對(duì)于(2E),(4Z)-4-(3-甲氧羰基苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-戊二烯酸甲酯(17a)量度=0.81mmol,產(chǎn)率=75%;
UVmax(CH3OH)326nm(ε=36,800),232nm(ε=20,900);1H NMR(300MHz,CDCl3)δ8.06(dt,J=2,8Hz,1H,4-ArH),7.87(t,J=2Hz,1H,4-ArH),7.67(d,J=16Hz,1H,CH=CHCO2),7.52(t,J=8Hz,1H,4-ArH),7.36(dt,J=2,8Hz,1H,4-ArH),7.07(d,J=8Hz,1H,5-ArH),6.90(s,1H,C=CH),6.82(d,J=2Hz,1H,5-ArH),6.72(dd,J=2,8Hz,1H,5-ArH),5.80(d,J=16Hz,1H,CH=CHCO2),3.88(s,3H,CO2CH3),3.70(s,3H,CO2CH3),1.51-1.60(m,4H,CH2CH2),1.17(s,6H,2×CH3),and 0.92(s,6H,2×CH3);13C NMR(75MHz,CDCl3)δ167.60(C=O),166.71(C=O),149.80,146.02,144.79,139.69,137.88,137.23,134.05,132.34,131.28,130.51,129.48,129.04,128.40,127.73,126.63,119.11,52.20(CO2CH3),51.52(CO2CH3),34.79,34.22,33.92,31.54,and 31.38;IR(film)2955,2860,1720(C=O),1615,1590,1435,1310,1280,1265,1205,1190,1170,1120,1095,1080,and 980cm-1;MS(DCI)m/e 433(MH+),401(M+-OCH3).
對(duì)于(2E),(4Z)-4-(3-甲氧羰基苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2,4-戊二烯酸(17b)量度=1.80mmol,產(chǎn)率=99%;
1H NMR(300MHz,CDCl3)δ8.08(dt,J=2,8Hz,1H,4-ArH),7.88(t,J=2Hz,1H,4-ArH),7.72(d,J=15Hz,1H,CH=CHCO2),7.53(d,J=12Hz,2H,ArH),7.45-7.51(m,2H,ArH),7.32-7.37(m,2H,ArH),7.01(s,1H,C=CH),6.67(dd,J=2,9Hz,1H,ArH),5.43(d,J=15Hz,1H,CH=CHCO2),3.89(s,2H,CO2CH3),3.72(s,3H,CO2CH3),1.71(s,4H,CH2CH2),and 1.17-1.23(m,15H,4×CH3and CO2CH2CH3);13C NMR(75MHz,CDCl3)δ167.64(C=O),166.77(C=O),149.50,145.74,144.99,142.30,139.97,138.77,137.86,137.49,134.28,133.62,132.13,131.35,131.12,130.62,129.37,129.19,126.91,125.44,124.66,123.01,119.41,52.25(CO2CH3),51.60(CO2CH3),34.96,34.67,32.44(4×CH3),and 29.73;IR(film)2955,2925,2860,1720(C=O),1615,1595,1460,1435,1365,1305,1295,1265,1210,1195,1170,1120,and 1110cm-1;MS(DCI)m/e 483(MH+),451(MH+-CH3OH).
對(duì)于(2E),(4Z)-4-(3-甲氧羰基苯基)-5-(3,4-雙戊氧苯基)-2,4-戊二烯酸甲酯(17c)量度=0.32mmol,產(chǎn)率=95%;
1H NMR(300MHz,CDCl3)δ8.03(dt,J=2,8Hz,1H,4-ArH),7.87(t,J=2Hz,1H,4-ArH),7.65(dd,J=1,15.5Hz,1H,CH=CHCO2),7.51(t,J=8Hz,1H,4-ArH),7.36(dt,J=2,8Hz,1H,4-ArH),6.86(d,J=1Hz,1H,C=CH),6.60-6.67(m,2H,2×5-ArH),6.28(d,J=2Hz,1H,5-ArH),5.32(d,J=15Hz,1H,CH=CHCO2),3.91(t,J=6.5Hz,2H,ArOCH2),3.88(s,3H,CO2CH3),3.63(s,3H,CO2CH3),3.40(t,J=6.5Hz,2H,ArOCH2),1.70-1.79(m,2H,ArOCH2CH2),1.54-1.59(m,2H,ArOCH2CH2),1.24-1.42(m,8H,2×CH2),and 0.85-0.95(m,6H,2×CH3);13C NMR(75MHz,CDCl3)δ167.65(C=O),166.57(C=O),148.72,148.23,139.38,137.94,136.04,134.21,131.31,130.69,129.46,128.95,128.05,124.54,118.53,113.91,112.59,68.91(ArOCH2),68.41(ArOCH2),52.21(CO2CH3),51.49(CO2CH3),28.75,28.59,28.10,27.95,22.40,22.34,and 14.00;IR(film)2950,2935,2870,1730(C=O),1715(C=O),1615,1590,1510,1470,1435,1395,1310,1275,1260,1240,1210,1190,1160,1140,1120,1095,1075,1015,985,and 740cm-1;MS(DCI)m/e 495(MH+),463(M+-OCH3).
對(duì)于(2E),(4Z)-4-(3-甲氧羰基苯基)-5-(3,4-雙癸氧苯基)-2,4-戊二烯酸甲酯(17d)量度=0.32mmol,產(chǎn)率=75%;
1H NMR(300MHz,CDCl3)δ8.04(dt,J=2,8Hz,1H,4-ArH),7.87(t,J=2Hz,1H,4-ArH),7.65(d,J=15Hz,1H,CH=CHCO2),7.51(t,J=8Hz,1H,4-ArH),7.36(dt,J=2,8Hz,1H,4-ArH),6.86(s,1H,C=CH),6.59-6.66(m,2H,2×5-ArH),6.28(d,J=2Hz,1H,5-ArH),5.32(d,J=15Hz,1H,CH=CHCO2),3.90(t,J=6.5Hz,2H,5-ArOCH2),3.88(s,3H,CO2CH3),3.70(s,3H,CO2CH3),3.40(t,J=6.5Hz,2H,5-ArOCH2),1.73(quintet,2H,5-ArOCH2CH2),1.50-1.65(m,2H,5-ArOCH2CH2),1.18-1.43(m,28H,14×CH2),and 0.83-0.89(m,6H,2×CH3);13C NMR(75MHz,CDCl3)δ167.67(C=O),166.57(C=O),149.74,149.64,148.21,139.40,137.94,136.02,134.21,131.30,130.69,129.46,128.95,128.02,124.49;118.51,113.91,112.57,68.91(ArOCH2),68.44(ArOCH2),52.22(CO2CH3),51.50(CO2CH3),31.92,31.89,29.58,29.33,29.06,28.92,25.92,25.79,22.68,and 14.12;IR(film)2950,2920,2870,2850,1720(C=O),1615,1585,1515,1470,1435,1310,1280,1245,1210,1195,1170,1145,1120,1090,1020,980,and 740cm-1;MS(DCI)m/e 635(MH+),603(M+-OCH3).
對(duì)于(2E),(4Z)-4-(3-乙氧羰基苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸乙酯(17e)量度=0.98mmol,產(chǎn)率=82%;除用乙醇鈉(21wt%于乙醇)代替甲醇鈉外,其余按一般方法制備。
1H NMR(300MHz,CDCl3)δ7.99(d,J=8Hz,1H,4-ArH),7.77(s,1H,4-ArH),7.51(d,J=16Hz,1H,CH=CHCO2),7.38(t,J=8Hz,1H,4-ArH),7.17(d,J=8Hz,1H,4-ArH),6.97(m,2H,7-ArH),6.81(d,J=8Hz,1H,7-ArH),6.21(t,J=8Hz,1H,C=CH),5.28(d,J=16Hz,1H,CH=CHCO2),4.37(q,J=7Hz,2H,CO2CH2CH3),4.15(q,J=7Hz,2H,CO2CH2CH3),2.63(t,J=7Hz,2H,ArCH2),2.27(q,J=7Hz,2H,ArCH2CH2),1.65(s,4H,CH2CH2),1.39(t,J=7Hz,3H,CO2CH2CH3),and 1.18-1.25(m,15H,4×CH3and CO2CH2CH3);13C NMR(75MHz,CDCl3)δ167.24(C=O),166.34(C=O),148.02,144.74,142.59,142.21,139.63,137.71,136.77,133.66,130.82,130.25,128.65,128.56,126.50,126.45,125.70,119.24,61.09(CO2CH2CH3),60.27(CO2CH2CH3),35.16,35.10,34.15,33.95,31.91,31.87,31.67,14.35(CO2CH2CH3),and 14.28(CO2CH2CH3);IR(film)2960,2930,1720(C=O),1625,1305,1280,1260,and 1175cm-1;MS(DCI)m/e 489(MH+),443(M-OCH2CH3)+.
實(shí)施例17合成化合物18的一般方法將酯17于甲醇/四氫呋喃/2N氫氧化鈉溶液(1∶1∶1,0.1M)中的混合物加熱回流1-4h。然后將反應(yīng)混合物冷卻至室溫,并加入10%鹽酸溶液,直至溶液達(dá)到PH1。用二氯甲烷萃取所得混濁混合物(分2批),有機(jī)相用鹽水洗滌,于無水硫酸鎂上干燥,過濾,并濃縮。自戊烷中蒸發(fā)殘余物(分3批),然后真空干燥。
對(duì)于(2E),(4Z)-4-(3-羧基苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-戊二烯酸(18a)量度=0.50mmol,產(chǎn)率=75%;
UVmax(CH3OH)324nm(ε=34,400),232nm(ε=19,100);1H NMR(300MHz,CD3OD)δ8.08(dt,J=2,8Hz,1H,4-ArH),7.84(t,J=2Hz,1H,4-ArH),7.71(d,J=16Hz,1H,CH=CHCO2),7.62(t,J=8Hz,1H,4-ArH),7.41(dt,J=2,8Hz,1H,4-ArH),7.15(d,J=8Hz,1H,5-ArH),7.03(s,1H,C=CH),6.87(dd,J=2,8Hz,1H,5-ArH),6.81(d,J=2Hz,1H,5-ArH),5.28(d,J=16Hz,1H,CH=CHCO2),1.54-1.60(m,4H,CH2CH2),1.18(s,6H,2×CH3),and 0.98(s,6H,2×CH3);13C NMR(75MHz,CD3OD)δ170.47(C=O),169.37(C=O),151.21,147.03,145.66,140.98,139.51,138.91,135.24,133.85,133.35,131.89,130.78,130.28,129.44,129.09,127.68,120.49,35.94,35.15,34.87,31.95,and 31.86;IR(film)3400(br,CO2H),2960,2925,2860,1685(C=O),1615,1590,1450,1410,1280,and 1215cm-1;MS(DCI)m/e 405(MH+),387(M+-OH).Anal.Calcd.for C26H28O4·0.25H2O:C,76.34;H,7.02.Found:C,76.21;H,6.85.
對(duì)于(2E),(4Z)-4-(3-羧基苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2,4-戊二烯酸(18b)量度=1.60mmol,產(chǎn)率=99%;
UVmax(CH3OH)342nm(ε=36,700),294nm(ε=27,500),284nm(ε=25,900);1H NMR(300MHz,DMSO-d6)δ7.86(brt,J=8Hz,1H,4-ArH),7.60-7.73(m,7H,6×ArH and CH=CHCO2),7.42-7.46(m,2H,ArH),7.37(s,1H,C=CH),5.23(d,J=15Hz,1H,CH=CHCO2),1.67(s,4H,CH2CH2),and 1.28(brs,12H,4×CH3);13C NMR(75MHz,DMSO-d6)δ167.29(C=O),166.91(C=O),148.78,145.20,144.56,139.34,137.76,137.21,133.88,132.07,131.65,131.11,130.91,130.17,129.88,129.75,128.95,126.70,125.084,124.81,124.52,120.14,34.41,34.34,34.22,and 32.17;IR(KBr)2400-3400(br,CO2H),3010,2960,2920,2860,1685(C=O),1610,1575,1450,1410,1365,1295,and 1215cm-1;MS(DCI)m/e 455(MH+)and 411(MH+-CO2H);Anal.Calcd.for C30H30O4·0.6H2OC,77.42;H,6.76.Found:C,77.37;H,6.93.
對(duì)于(2E),(4Z)-4-(3-羧基苯基)-5-(3,4-雙戊氧苯基)-2,4-戊二烯酸(18c)量度=0.16mmol,產(chǎn)率=95%;
UVmax(CH3OH)346nm(ε=28,500),230nm(ε=18,400);1H NMR(300MHz,CD3OD)δ8.09(dt,J=2,8Hz,1H,4-ArH),7.86(t,J=2Hz,1H,4-ArH),7.70(d,J=15.5Hz,CH=CHCO2),7.63(t,J=8Hz,1H,4-ArH),7.42(dt,J=2,8Hz,1H,4-ArH),6.99(s,1H,C=CH),6.73-6.80(m,2H,5-ArH),6.30(d,J=2Hz,1H,5-ArH),5.26(d,J=15Hz,1H,CH=CHCO2),3.92(t,J=6.5Hz,2H,ArOCH2),3.37(t,J=6.5Hz,2H,ArOCH2),1.68-1.77(m,2H,ArOCH2CH2),1.50-1.56(m,2H,ArOCH2CH2),1.27-1.46(m,8H,4×CH2),and 0.84-0.98(m,6H,2×CH3);13C NMR(75MHz,CD3OD)δ170.50(C=O),169.00(C=O),151.33,151.12,149.50,140.68,139.52,137.65,135.39,132.01,130.84,130.28,129.69,126.35,119.86,115.07,114.06,70.02(ArOCH2),69.60(ArOCH2),29.99,29.78,29.37,29.19,23.48,23.41,and 14.39;IR(film)2000-3400(br,CO2H),1695(C=O),1680(C=O),1615,1580,1510,1465,1430,1315,1270,1240,1210,and 1140cm-1;MS(DCI)m/e 467(MH+),449(M+-OH).Anal.Calcd.for C28H34O6:C,72.08;H,7.34;Found:C,72.84;H,7.84.
對(duì)于(2E),(4Z)-4-(3-羧基苯基)-5-(3,4-雙癸氧苯基)-2,4-戊二烯酸(18d)量度=0.21mmol,產(chǎn)率=96%;
mp 151-154℃;UVmax(CH3OH)354nm(ε=30,700),242nm(ε=15,200);1H NMR(300MHz,CDCl3)δ8.12(dt,J=2,8Hz,1H,4-ArH),7.96(t,J=2Hz,1H,4-ArH),7.75(d,J=15Hz,CH=CHCO2),7.55(t,J=8Hz,1H,4-ArH),7.42(dt,J=2,8Hz,1H,4-ArH),6.92(s,1H,C=CH),6.61-6.68(m,2H,5-ArH),6.30(d,J=2Hz,1H,5-ArH),5.31(d,J=15Hz,1H,CH=CHCO2),3.91(t,J=6.5Hz,2H,ArOCH2),3.42(t,J=6.5Hz,2H,ArOCH2),1.74(quintet,2H,ArOCH2CH2),1.50-1.65(m,2H,ArOCH2CH2),1.20-1.45(m,28H,14×CH2),and 0.82-0.88(m,6H,2×CH3);13C NMR(75MHz,CDCl3)δ172.58(C=O),171.44(C=O),149.92,148.25,137.91,135.69,135.00,131.35,130.60,129.62,127.81,124.76,118.00,114.06,112.58,68.91(ArOCH2),68.44(ArOCH2),31.92,31.89,29.58,29.33,29.06,28.92,25.92,25.79,22.68,and 14.12;IR(film)2300-3600(br,CO2H),2925,2855,1685(C=O),1615,1585,1510,1470,1450,1415,1310,1270,1240,1205,and 1140cm-1;MS(DCI)m/e 607(MH+),589(M+-OCH3).Anal.Calcd.for C38H54O6:C,75.21;H,8.97;Found:C,75.30;H,8.96.
對(duì)于(2E),(4Z)-4-(3-羧基苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸(18e)量度=0.53mmol,產(chǎn)率=39%;
1H NMR(300MHz,DMSO-d6)δ12.63(brs,2H,CO2H),7.90(d,J=7Hz,1H,4-ArH),7.57(s,1H,4-ArH),7.44(m,2H,CH=CHCO2and 4-ArH),7.13(d,J=8Hz,1H,4-ArH),6.96(m,2H,7-ArH),6.76(d,J=8Hz,1H,7-ArH),6.36(t,J=8Hz,1H,C=CH),5.05(d,J=16Hz,1H,CH=CHCO2),2.57(m,2H,ArCH2),2.15(m,2H,ArCH2CH2),1.57(s,4H,CH2CH2),1.17(s,6H,2×CH3),and 1.13(s,6H,2×CH3);13C NMR(75MHz,DMSO-d6)δ167.36(C=O),167.34(C=O),147.60,143.97,142.24,141.82,138.91,137.67,136.39,133.32,131.03,129.60,128.84,128.42,126.14,125.58,119.21,34.65,34.33,33.72,33.55,31.64,and 31.59;IR(KBr)2400-3600(br,CO2H),2960,2930,1690(C=O),1620,1450,1310,and 1290cm-1;MS(DCI)m/e 432(MH+),417(M-CH2)+,415(M-OH)+,387;Anal.Calcd.for C28H32O4·0.2H2O:C,77.12;H,7.49.Found:C,76.76;H,7.43.
實(shí)施例18合成化合物19的一般方法于室溫及氬氣環(huán)境下,依次用二乙基膦酰乙酸甲酯(1.5當(dāng)量)和甲醇鈉(25wt%于甲醇,1.4當(dāng)量)處理醛12(1當(dāng)量)的無水甲苯(0.1M)溶液。于室溫?cái)嚢璺磻?yīng)混合物12-16h,再加入甲醇鈉(25wt%于甲醇,1當(dāng)量)處理。攪拌混合物0.5h,然后在乙醚和飽和氯化銨溶液之間分配。有機(jī)層用飽和氯化鈉溶液洗滌,于無水硫酸鎂上干燥,過濾并濃縮。經(jīng)硅膠柱層析純化(40∶1硅膠/粗產(chǎn)物;用5%乙酸乙酯的己烷洗脫),得到所需產(chǎn)物。
對(duì)于(2E),(4Z)-4-(3-三氟甲苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸(19a)量度=0.49mmol,產(chǎn)率=86%;
1H NMR(300MHz,CDCl3)δ7.54(brd,J=8Hz,1H,4-ArH),7.48(d,J=15Hz,1H,CH=CHCO2),7.41(t,J=8Hz,1H,4-ArH),7.24(s,1H,4-ArH),7.16(d,J=8Hz,1H,4-ArH),6.94-6.96(m,2H,7-ArH),6.78(dd,J=2,8Hz,1H,7-ArH),6.21(t,J=8Hz,1H,C=CH),5.23(d,J=15Hz,1H,CH=CHCO2),3.68(s,3H,CO2CH3),2.61(t,J=8Hz,2H,ArCH2),2.24(q,J=8Hz,2H,ArCH2CH2),1.63(brs,4H,CH2CH2),1.24(s,6H,2×CH3),and 1.20(s,6H,2×CH3);13C NMR(75MHz,CDCl3)δ167.55(C=O),147.98,144.79,142.73,139.12,137.49,137.20,132.63,128.97,126.56,126.48,125.86,(q,J3c,f=4Hz,4-ArC),125.67,124.37(q,J3c,f=4Hz,4-ArC),118.81,51.54(CO2CH3),35.10,35.06,34.13,33.95,31.87,31.83,and 31.69;IR(film)2960,2926,2860,1720(C=O),1625,1435,1325,1310,1295,1270,1170,1130,1110,1070,and 705cm-1;MS(DCI)m/e 471(MH+).
對(duì)于(2E),(4Z)-4-(4-氟苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸甲酯(19b)量度=0.85mmol,產(chǎn)率=84%;
1H NMR(300MHz,CDCl3)δ7.46(d,J=16Hz,1H,CH=CHCO2),7.16(d,J=8Hz,1H,7-ArH),6.72-7.00(m,6H,4×4-ArH and 2×7-ArH),6.15(t,J=8Hz,1H,C=CH),5.27(d,J=16Hz,1H,CH=CHCO2),3.68(s,3H,CO2CH3),2.61(t,J=8Hz,2H,ArCH2),2.25(q,J=8Hz,2H,ArCH2CH2),1.64(brs,4H,CH2CH2),1.24(s,6H,2×CH3),and 1.22(s,6H,2×CH3);13C NMR(75MHz,CDCl3)δ167.74,148.66,144.72,142.61,142.29,139.54,137.69,130.78(d,J3c,f=8Hz,4-ArC),126.50,125.78,118.56,115.31(d,J2c,f=21Hz,4-ArC),51.47(CO2CH3),35.11,35.08,35.00,34.13,33.94,31.90,31.85 and 31.66;IR(film)2960,2925,2860,1720(C=O),1625,1510,1460,1435,1305,1270,1225,1190,1170,845,and 825 cm-1;MS(DCI)m/e 421(MH+).
對(duì)于(2E),(4Z)-4-(3-氟苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸(19c)量度=1.09mmol,產(chǎn)率=81%;
1H NMR(300MHz,CDCl3)δ7.45(d,J=15Hz,1H,CH=CHCO2),7.21-7.28(m,1H,4-ArH),7.17(d,J=2Hz,1H,7-ArH),6.92-6.99(m,2H,1×4-ArH and 1×7-ArH),6.79(dd,J=2,8Hz,1H,7-ArH),6.61(dt,J=2,8Hz,1H,4-ArH),6.49(dq,J=2,8Hz,1H,4-ArH),6.15(t,J=8Hz,1H,C=CH),5.29(d,J=15Hz,1H,CH=CHCO2),3.71(s,3H,CO2CH3),2.62(t,J=8Hz,2H,ArCH2),2.26(q,J=8Hz,2H,ArCH2CH2),1.64(brs,4H,CH2CH2),1.24(s,6H,2×CH3),and 1.20(s,6H,2×CH3);13C NMR(75MHz,CDCl3)δ167.69(C=O),148.09,144.76,142.66,142.22,139.35,138.56(d,J3c,f=9Hz,4-ArC),137.59,129.90(d,J3c,f=9Hz,4-ArC),126.49,125.75,124.86,118.66,116.13(d,J2c,f=21Hz,4-ArC),114.33(d,J2c,f=21Hz,4-ArC),51.49(CO2CH3),35.08,34.98,34.13,33.95,31.84,and 31.68;IR(film)2960,2925,2860,1720(C=O),1625,1610,1580,1435,1305,1265,1190,and 1170 cm-1;MS(DCI)m/e 421(MH+).
對(duì)于(2E),(4Z)-4-苯基-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸甲酯(19d)量度=0.63mmol,產(chǎn)率=91%;
1H NMR(300MHz,CDCl3)δ7.48(d,J=15Hz,1H,CH=CHCO2),7.23-7.32(m,3H,4-ArH),7.16(d,J=8Hz,1H,7-ArH),6.96(d,J=2Hz,1H,7-ArH),6.84-6.88(m,2H,4-ArH),6.79(dd,J=2,8Hz,1H,7-ArH),6.15(t,J=8Hz,1H,C=CH),5.33(d,J=15Hz,1H,CH=CHCO2),3.69(s,3H,CO2CH3),2.61(t,J=8Hz,2H,ArCH2),2.27(q,J=8Hz,2H,ArCH2CH2),1.64(brs,4H,CH2CH2),1.24(s,6H,2×CH3),and 1.21(s,6H,2×CH3);13C NMR(75MHz,CDCl3)δ167.87(C=O),148.78,144.68,142.51,141.87,140.53,137.83,136.32,129.11,128.34,127.32,126.46,125.74,118.51,51.40(CO2CH3),35.15,35.10,34.13,33.93,31.90,31.85,and 31.59;IR(film)2960,2925,2860,1720(C=O),1620,1495,1455,1435,1305,1265,1190,1170,1105,980,825,and 700cm-1;MS(DCI)m/e 403(MH+).
對(duì)于(2E),(4Z)-4-(3-三氟甲苯基)-7-[3-(1-金剛烷基)-4-甲氧苯基]-2,4-庚二烯酸(19e)量度=0.30mmol,產(chǎn)率=81%;
1H NMR(300MHz,CDCl3)δ7.55(d,J=8Hz,1H,4-ArH),7.50(d,J=16Hz,1H,CH=CHCO2),7.43(t,J=8Hz,1H,4-ArH),7.14(s,1H,4-ArH),7.04(d,J=8Hz,1H,4-ArH),6.87(d,J=2Hz,1H,7-ArH),6.82(dd,J=2,8Hz,1H,7-ArH),6.73(d,J=8Hz,1H,7-ArH),6.21(t,J=8Hz,1H,C=CH),5.23(d,J=16Hz,1H,CH=CHCO2),3.78(s,3H,ArOCH3),3.69(s,3H,CO2CH3),2.62(t,J=7Hz,2H,ArCH2),2.23(q,J=7Hz,2H,ArCH2CH2),2.02(s,9H,adamantyl),and 1.73(s,6H,adamantyl);13C NMR(75MHz,CDCl3)δ167.54(C=O),157.24,148.05,142.85,139.13,138.32,137.24,132.66,132.16,130.91(d,J2c,f=32Hz,4-ArC),128.94,126.89,126.29,125.79(d,J3c,f=4Hz,4-ArC),124.32(d,J3c,f=4Hz,4-ArC),118.76,111.62,55.01(ArOCH3),51.52(CO2CH3),40.57,37.09,36.86,34.76,32.00,and 29.07;IR(film)2905,2850,1720(C=O),1325,1235,1170,and 1130cm-1;MS(DCI)m/e 525(MH+),255,135(C10H15+);Anal.Calcd for C32H35O3F3:C,73.26;H,6.72.Found:C,73.58;H,6.70.
對(duì)于(2E),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-甲氧苯基]-2,4-庚二烯酸(19f)量度=0.46mmol,產(chǎn)率=66%;
1H NMR(300MHz,CDCl3)δ7.55(d,J=8Hz,1H,4-ArH),7.49(d,J=16Hz,1H,CH=CHCO2),7.42(t,J=8Hz,1H,4-ArH),7.24(s,1H,4-ArH),7.07(d,J=8Hz,1H,4-ArH),6.95(d,J=8Hz,1H,7-ArH),6.59(dd,J=8,2Hz,1H,7-ArH),6.50(d,J=1Hz,1H,7-ArH),6.21(t,J=8Hz,1H,C=CH),5.24(d,J=16Hz,1H,CH=CHCO2),3.73(s,3H,ArOCH3),3.69(s,3H,CO2CH3),2.64(t,J=7Hz,2H,ArCH2),2.26(q,J=7Hz,2H,ArCH2CH2),2.05(s,9H,adamantyl),and 1.74(s,6H,adamantyl);13C NMR(75MHz,CDCl3)δ167.53(C=O),158.75,147.90,142.48,139.23,137.20,136.45,132.72,130.90(d,J2c,f=32Hz,4-ArC),128.97,126.42,125.84(d,J3c,f=4Hz,4-ArC),124.35(d,J3c,f=4Hz,4-ArC),120.31,118.93,111.89,54.84(ArOCH3),51.54(CO2CH3),40.63,37.13,36.68,34.92,31.58,and 29.10;IR(film)2905,2850,1720(C=O),1325,1310,1170,1130,and 1070cm-1;MS(DCI)m/e 525(MH+),493(M-OCH3)+,135(C10H15)+;Anal.Calcd for C32H35O3F3:C,73.26;H,6.72.Found:C,73.09;H,6.50.
實(shí)施例19合成化合物20的一般方法將酯19于甲醇/四氫呋喃/2N氫氧化鈉溶液(1∶1∶1,0.1M)中的混合物加熱回流1-4h。然后冷卻至室溫,加入10%鹽酸溶液至溶液達(dá)到PH1。用二氯甲烷萃取所得混濁混合物(兩批),有機(jī)相用鹽水洗滌,于無水硫酸鎂上干燥,過濾,濃縮。自戊烷中蒸發(fā)殘余物(三批),然后真空干燥。
對(duì)于(2E),(4Z)-4-(3-三氟甲苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸(20a)量度=0.39mmol,產(chǎn)率=94%;
UVmax(CH3OH)260nm(ε=23,200);1H NMR(300MHz,CD3OD)δ7.61(brd,J=8Hz,1H,4-ArH),7.51(d,J=15Hz,1H,CH=CHCO2),7.48(t,J=8Hz,1H,4-ArH),7.18(d,J=8Hz,1H,4-ArH),7.16(s,1H,4-ArH),6.97(d,J=2Hz,1H,7-ArH),6.83(d,J=8Hz,1H,7-ArH),6.76(dd,J=2,8Hz,1H,7-ArH),6.31(t,J=8Hz,1H,C=CH),5.08(d,J=15Hz,1H,CH=CHCO2),2.65(t,J=8Hz,2H,ArCH2),2.20(q,J=8Hz,2H,ArCH2CH2),1.67(brs,4H,CH2CH2),1.25(s,6H,2×CH3),and 1.20(s,6H,2×CH3);13C NMR(75MHz,CD3OD)δ170.45(C=O),149.55,145.61,144.14,143.58,140.63,139.03,138.89,134.26,130.40,127.84,127.61,126.97(q,J3c,f=4Hz,2-ArC),125.28(q,J3c,f=4Hz,2-ArC),120.23,36.30,35.87,35.06,34.88,33.17,and 32.33;IR(film)2400-3600(br,CO2H),2960,2930,2860,1690(C=O),1620,1460,1415,1365,1325,1310,1275,1205,1165,1130,and 1070cm-1;MS(DCI)m/e 457(MH+).Anal.Calcd.for C28H31O2F3:C,73.66;H,6.84.Found:C,73.41;H,6.84.
對(duì)于(2E),(4Z)-4-(4-氟苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸(20b)量度=0.66mmol,產(chǎn)率=88%;
UVmax(CH3OH)264nm(ε=24,300);1H NMR(300MHz,CD3OD)δ7.47(d,J=16Hz,1H,CH=CHCO2),7.18(d,J=8Hz,1H,7-ArH),6.96-7.08(m,3H,ArH),6.76(dd,J=2,8Hz,1H,7-ArH),6.62-6.69(m,2H,ArH),6.22(t,J=8Hz,1H,C=CH),5.13(d,J=16Hz,1H,CH=CHCO2),2.63(t,J=8Hz,2H,ArCH2),2.21(q,J=8Hz,2H,ArCH2CH2),1.67(brs,4H,CH2CH2),1.26(s,6H,2×CH3),and 1.20(s,6H,2×CH3);13C NMR(75MHz,CD3OD)δ170.69,163.45(d,J1c,f=246Hz,4-ArC),150.22,145.58,143.59,141.13,139.21,133.76,132.19(d,J3c,f=8Hz,4-ArC),127.88,127.55,126.85,120.84,116.14(d,J2c,f=21Hz,4-ArC),36.32,35.92,35.06,34.88,33.19,32.38,and 32.36;IR(film)2400-3600(br,CO2H),2960,2925,2860,1690(C=O),1615,1510,1495,1460,1415,1155,985,840,and 825cm-1;MS(DCI)m/e 407(MH+).Anal.Calcd.for C27H31O2F·0.1H2O:C,79.41;H,7.70.Found:C,79.27;H,7.67.
對(duì)于(2E),(4Z)-4-(3-氟苯基)-7-(5,6,7,8-四甲基-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸(20c)量度=0.65mmol,產(chǎn)率=48%;
UVmax(CH3OH)262nm(ε=24,900);1H NMR(300MHz,CD3OD)δ7.47(d,J=15Hz,1H,CH=CHCO2),7.25-7.33(m,1H,4-ArH),7.18(d,J=2Hz,1H,7-ArH),6.97-7.04(m,2H,1×4-ArH and 1×7-ArH),6.76(dd,J=2,8Hz,1H,7-ArH),6.51(dt,J=2,8Hz,1H,4-ArH),6.30(dq,J=2,8Hz,1H,4-ArH),6.24(t,J=8Hz,1H,C=CH),5.12(d,J=15Hz,1H,CH=CHCO2),2.64(t,J=8Hz,2H,ArCH2),2.22(q,J=8Hz,2H,ArCH2CH2),1.67(brs,4H,CH2CH2),1.26(s,6H,2×CH3),and 1.20(s,6H,2×CH3);13C NMR(75MHz,CD3OD)δ170.53(C=O),148.75,145.00,143.58,141.00,140.15,139.09(d,J3c,f=9Hz,4-ArC),131.18(d,J3c,f=9Hz,4-ArC),127.87,127.52,127.10,126.25,120.01,117.05(d,J2c,f=21Hz,4-ArC),115.17(d,J2c,f=21Hz,4-ArC),36.31,35.88,35.06,34.89,33.22,and 32.34;IR(film)2300-3600(br,CO2H),2960,2925,2860,1685(C=O),1605,1580,1490,1455,1425,1385,1360,1320,1310,1265,1250,1200,915,880,825,795,and 695cm-1;MS(DCI)m/e 407(MH+).Anal.Calcd.for C27H31O2F:C,79.77;H,7.69.Found:C,79.74;H,7.63.
對(duì)于(2E),(4Z)-4-苯基-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸(20d)量度=0.63mmol,產(chǎn)率=91%;
1H NMR(300MHz,CD3OD)δ7.48(d,J=15Hz,1H,CH=CHCO2),7.27-7.33(m,3H,4-ArH),7.17(d,J=8Hz,1H,7-ArH),6.96(d,J=2Hz,1H,7-ArH),6.70-6.78(m,3H,2×4-ArH and 1×7-ArH),6.20(t,J=8Hz,1H,C=CH),5.15(d,J=15Hz,1H,CH=CHCO2),2.62(t,J=8Hz,2H,ArCH2),2.22(q,J=8Hz,2H,ArCH2CH2),1.67(brs,4H,CH2CH2),1.25(s,6H,2×CH3),and 1.20(s,6H,2×CH3);13C NMR(75MHz,CD3OD)δ150.42,145.54,145.46,143.46,143.13,142.17,139.26,137.77,130.27,129.40,128.41,127.78,127.50,127.06,119.93,36.34,36.02,35.06,34.87,33.14,and 32.36;IR(KBr)2400-3300(br,CO2H),3020,2955,2925,2865,1690(C=O),1615,1600,1495,1460,1440,1415,1385,1360,1310,1300,1285,1275,1250,1235,1200,990,820,and 695cm-1;MS(DCI)m/e 389(MH+),371(M+-OH).Anal.Calcd.for C27H32O2:C,83.46;H,8.30.Found:C,83.51;H,8.58.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-7-[3-(1-金剛烷基)-4-甲氧苯基]-2,4-庚二烯酸(20e)量度=0.19mmol,產(chǎn)率=87%;
1H NMR(300MHz,CDCl3)δ7.57(m,2H,4-ArH and CH=CHCO2),7.44(t,J=8Hz,1H,4-ArH),7.15(s,1H,4-ArH),7.05(d,J=8Hz,1H,4-ArH),6.87(d,J=2Hz,1H,7-ArH),6.82(dd,J=2,8Hz,1H,7-ArH),6.73(d,J=8Hz,1H,7-ArH),6.27(t,J=8Hz,1H,C=CH),5.23(d,J=16Hz,1H,CH=CHCO2),3.79(s,3H,ArOCH3),2.63(t,J=7Hz,2H,ArCH2),2.25(q,J=7Hz,2H,ArCH2CH2),2.03(s,9H,adamantyl),and 1.73(s,6H,adamantyl);13C NMR(75MHz,CDCl3)δ172.20(C=O),157.27,150.14,144.20,139.11,138.36,136.95,132.63,132.05,130.97(d,J2c,f=32Hz,4-ArC),129.02,126.87,126.28,125.80,124.42,118.14,111.64,55.01(OCH3),40.57,37.10,36.87,34.69,32.08,and 20.07;IR(KBr)2400-3700(br,CO2H),2905,2850,1690,1615,1325,1235,1165,and 1130cm-1;MS(DCI)m/e 511(MH+),493(M-OH)+,465,255,135(C10H15)+;Anal.Calcd for C31H33O3F3:C,72.92;H,6.51.Found:C,72.50;H,6.68.
對(duì)于(2Z),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-甲氧苯基]-2,4-庚二烯酸(20f)量度=0.24mmol,產(chǎn)率=69%;
1H NMR(300MHz,CDCl3)δ7.55(m,2H,4-ArH and CH=CHCO2),7.43(t,J=8Hz,1H,4-ArH),7.24(d,J=1Hz,1H,4-ArH),7.07(d,J=8Hz,1H,4-ArH),6.95(d,J=8Hz,1H,7-ArH),6.59(dd,J=8,2Hz,1H,7-ArH),6.50(d,J=2Hz,1H,7-ArH),6.26(t,J=8Hz,1H,C=CH),5.23(d,J=16Hz,1H,CH=CHCO2),3.73(s,3H,ArOCH3),2.64(t,J=7Hz,2H,ArCH2),2.28(q,J=8Hz,2H,ArCH2CH2),2.05(s,9H,adamantyl),and 1.74(s,6H,adamantyl);13C NMR(75MHz,CDCl3)δ172.34(C=O),158.77,150.00,143.82,139.22,139.18,136.89,136.51,132.69,130.98(d,J2c,f=32Hz,4-ArC),129.04,126.45,125.80,124.46,122.14,120.29,118.35,111.88,54.85(OCH3),40.63,37.13,36.69,34.84,31.66,and 29.10;IR(KBr)2400-3600(br,CO2H),2905,2850,1690(C=O),1615,1325,1165,and 1130cm-1;MS(DCI)m/e 511(MH+),493(M-OH)+,135(C10H15)+;Anal.Calcd for C31H33O3F3:C,72.92;H,6.51.Found:C,72.79;H,6.60.
實(shí)施例20合成3-(叔丁基二苯基甲硅烷氧甲基)-溴苯(22)將3-溴芐醇(21)(10.0g,53.5mmol)、4-二甲基氨基吡啶(0.33g,2.7mmol)和叔丁基氯二苯基甲硅烷(17.6g,64.2mmol)在無水CH2Cl2(240ml)中的攪拌溶液在氬氣環(huán)境下冷卻至0℃。注射滴加三乙胺(8.1g,80.2mmol),并在3.5h內(nèi)將反應(yīng)混合物溫?zé)嶂潦覝?,水洗反?yīng)溶液,再次用CH2Cl2萃取水相,合并有機(jī)相,依次用1 NHCl、水和飽和氯化鈉溶液洗滌,于無水硫酸鎂上干燥,過濾,并濃縮,得到25.3g化合物22,為透明、淺黃色油狀物。經(jīng)柱層析純化(20∶1硅膠/粗產(chǎn)物;用5%-7.5%乙酸乙酯/己烷洗脫),得到21.2g(93%)化合物22的淺黃色油狀物。
1H NMR(300MHz,CDCl3)δ7.63-7.65(m,4H,ArH),7.35-7.48(m,8H,ArH),7.18-7.28(m,2H,ArH),4.72(s,2H,CH2OSi),and 1.05(s,9H,SiC(CH3)3).
實(shí)施例21合成3-(叔丁基二苯基甲硅烷氧甲基)芐醇(23)稱量鎂屑(1.45g,59.5mmol)至燒瓶中,然后真空火焰干燥。通氣氬氣,并加入無水THF(30ml)和二溴乙烷(約0.1ml)。于室溫下攪拌混合物。經(jīng)套管加入約25ml化合物22(21.1g,49.6mmol)的無水THF(120ml)溶液。溶液在10內(nèi)變?yōu)樯铧S棕色。然后通過套管加入剩余的化合物22的溶液,整個(gè)反應(yīng)溶液加熱回流2h后冷卻至室溫,加入對(duì)-甲醛(2.98g,99.2mmol)。于室溫?cái)嚢璺磻?yīng)混合物19h,然后倒入裝有飽和氯化銨溶液的分液漏斗。用乙醚萃取水溶性混合物兩次。合并有機(jī)層,用飽和氯化鈉溶液洗滌,于無水硫酸鎂上干燥,過濾,濃縮,得到19.1g透明、黃色液體。經(jīng)柱層析純化(10∶1硅膠/粗產(chǎn)物;用10%-30%乙酸乙酯/己烷進(jìn)行梯度洗脫),得到11.9g(64%)化合物23,為淺黃色油狀物;
1H NMR(300MHz,CDCl3)δ7.69-7.73(m,4H,ArH),7.25-7.46(m,10H,ArH),4.79(s,2H,CH2OSi),4.68(s,2H,CH2OH),and 1.11(s,9H,SiC(CH3)3);13C NMR(75MHz,CDCl3)δ141.32,140.67,135.48,133.35,129.61,128.41,127.62,125.46,125.29,124.54,65.32(CH2OSi,CH2OH),26.75(SiC(CH3)3),and 19.22(SiC(CH3)3);IR(film)3340(br,OH),2940,2860,1475,1430,1150,and 1110cm-1;MS(FAB)m/e 399(M+Na)+.
實(shí)施例22合成3-(叔丁基二苯基甲硅烷氧甲基)芐醇(24)于0℃、氬氣環(huán)境下,將甲磺酰氯(3.96g,34.6mmol)滴加至化合物23(11.8g,31.4mmol)、LiCl(1.33g,31.4mmol)和s-可力丁(4.19g,34.6mmol)的無水DMF(120ml)攪拌溶液中。將反應(yīng)混合物在2h內(nèi)溫?zé)嶂潦覝兀缓蟮谷胨?,并用乙醚萃?次。合并有機(jī)相,用飽和氯化鈉溶液洗滌,于無水硫酸鎂上干燥,過濾并濃縮,得到11.8g(95%)化合物24,為透明、深黃色液體。該氯化物不經(jīng)純化直接用于下一反應(yīng)。
1H NMR(300MHz,CDCl3)δ7.72-7.76(m,4H,ArH),7.31-7.48(m,10H,ArH),4.82(s,2H,CH2OSi),4.62(s,2H,CH2Cl),and 1.15(s,9H,SiC(CH3)3);13C NMR(75MHz,CDCl3)δ141.71,137.35,135.58,135.51,133.39,129.74,129.60,128.64,127.74,127.08,126.20,126.06,65.24(CH2OSi),46.34(CH2Cl),26.84(SiC(CH3)3),and 19.32(SiC(CH3)3);MS(DCI)m/e 395(MH+).
實(shí)施例23合成[3-(叔丁基二苯基甲硅烷氧甲基)苯基]乙腈(25)于室溫及氬氣環(huán)境下,向化合物24(11.8g,29.9mmol)的無水DMF(90ml)攪拌溶液中加入氰化鈉(1.57g,32.0mmol)和碘化四丁銨(0.11g,0.30mmol)。于80℃加熱反應(yīng)混合物2h后冷卻至室溫,并倒入飽和氯化銨溶液中,用乙醚萃取兩次。合并有機(jī)相,用飽和氯化鈉洗滌,于無水硫酸鎂上干燥,過濾,并濃縮,得到11.0g棕色透明油狀物。經(jīng)柱層析純化(20∶1硅膠/粗產(chǎn)物;用1%-10%乙酸乙酯/己烷進(jìn)行梯度洗脫),得到8.93g(73%)化合物25,為淺黃色透明油狀物。
1H NMR(300MHz,CDCl3)δ7.64-7.67(m,4H,ArH),7.19-7.41(m,10H,ArH),4.74(s,2H,CH2OSi),3.70(s,2H,CH2CN),and 1.08(s,9H,SiC(CH3)3);13C NMR(75MHz,CDCl3)δ142.24,135.57,133.31,129.81,129.04,127.78,126.41,125.69,125.54,117.87(CN),65.13(CH2OSi),26.85(SiC(CH3)3),23.65(CH2CN),and 19.31(SiC(CH3)3);IR(film)2960,2930,2890,2860,2250(CN),1470,1430,1150,1110,and 1080cm-1;MS(DCI)m/e 386(MH+).
實(shí)施例24合成(4E)-2-[3-(叔丁基二苯基甲硅烷氧基甲基]-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-4-己烯腈(26)將二異丙胺(0.23g,2.25mmol)的無水THF(2ml)溶液在氬氣環(huán)境下冷卻至0℃,并用注射滴入的n-BuLi(1.4M于己烷,1.46ml,2.05mmol)處理。攪拌溶液30min,冷卻至-78℃。通過套管加入化合物25(0.73g,2.05mmol)的無水THF(4ml)溶液。攪拌所得橙色溶液30min,然后通過套管加至冷卻至-78℃的化合物36(0.92g,2.86mmol)的無水THF(15ml)溶液中。在4h內(nèi)溫?zé)岱磻?yīng)混合物至室溫,倒入裝有飽和氯化銨溶液和乙醚的分液漏斗中。攪拌分層,并用飽和氯化鈉溶液洗滌有機(jī)相,于無水硫酸鎂上干燥,過濾并濃縮,得到1.55g黃色透明油狀物。通過柱層析純化(30∶1硅膠/粗產(chǎn)物;用1%-5%乙酸乙酯/己烷梯度洗脫),得到0.77g(60%)化合物26,為深黃色透明油狀物。
1H NMR(300MHz,CDCl3)δ7.66-7.69(m,4H,ArH),7.07-7.44(m,13H,ArH),5.71(t,J=6Hz,1H,CH=C),4.77(s,2H,CH2OSi),3.86(t,J=6Hz,1H,CHCN),2.71-2.86(m,2H,CH2CHCN),1.92(s,3H,C=CCH3),1.67(s,4H,CH2CH2),1.27(s,6H,2×CH3),1.27(s,6H,2×CH3),and 1.09(s,9H,SiC(CH3)3);13C NMR(75MHz,CDCl3)δ143.88,142.03,135.44,135.30,133.20,129.66,128.80,127.65,126.27,125.87,125.60,124.80,123.67,123.09,120.74,120.53(CN),65.07(CH2OSi),37.55(CHCN),35.03,34.92,34.17,33.95,31.75,31.69,27.82(SiC(CH3)3),19.20(SiC(CH3)3),and 16.01;IR(film)2960,2930,2860,2240(CN),1460,1430,1110,and 1080cm-1;MS(DCI)m/e 626(MH+).
實(shí)施例25合成(4E)-2-[3-(叔丁基二苯基甲硅烷氧甲基)苯基]-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-4-己醛(27)于0℃及氬氣環(huán)境下,將氫化二異丁銨(1.0M于己烷,1.54ml,1.54mmol)滴加至化合物26(0.74g,1.18mmol)的無水乙醚(22ml)溶液中。在2.5h內(nèi)溫?zé)岱磻?yīng)混合物至室溫,用乙酸乙酯(2.5ml)和1NH2SO4溶液(5ml)終止反應(yīng),并繼續(xù)攪拌10min。將混合物倒入分液漏斗中分層。用乙醚再次萃取水相,合并有機(jī)層,依次用1N NaOH溶液和飽和氯化鈉溶液洗滌,真空干燥后得到0.72g(97%)化合物27,為深黃色油狀物。1H-NMR顯示存在少量雜質(zhì),但該化合物在硅膠上分解。該物質(zhì)不經(jīng)純化直接用于下一反應(yīng)。
1H NMR(300MHz,CDCl3)δ9.73(s,1H,CHO),7.61-7.77(m,4H,ArH),7.03-7.42(m,13H,ArH),5.62(t,J=9Hz,1H,CH=C),4.78(s,2H,CH2OSi),3.66(t,J=6Hz,1H,CHCHO),2.92-3.01(m,1H,1×CH2CH),2.55-2.67(m,1H,1×CH2CH),1.95(s,3H,C=CCH3),1.66(s,4H,CH2CH2),1.28(s,12H,4×CH3),and 1.07(s,9H,SiC(CH3)3).
實(shí)施例26合成(2Z),(6E)-4-[3-(叔丁基二苯基甲硅烷氧甲基)苯基]-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,6-辛二烯酸甲酯(28)于-78℃及氬氣條件下,將雙(三甲基甲硅烷基)氨化鉀(0.5M于甲苯,2.28ml,1.14mmol)加至18-冠-6(1.51g,5.72mmol)、雙(2,2,2-三氟乙基)(甲氧羰基甲基)膦酸酯(0.36g,1.14mmol)和化合物27(0.72g,1.14mmol)的無水THF(16.5ml)攪拌溶液中。于-78℃維持反應(yīng)混合物1h,然后在3h內(nèi)溫?zé)嶂潦覝亍⑷芤旱谷胙b有飽和氯化銨溶液的分液漏斗中,并用乙醚萃取2次。合并有機(jī)相,用飽和氯化鈉溶液洗滌,于無水硫酸鎂上干燥,過濾并濃縮,得到0.85g淺黃色油狀物,經(jīng)柱層析純化(40∶1硅膠/粗產(chǎn)物;1%-5%乙酸乙酯/己烷梯度洗脫),得到0.42g(53%)化合物28,為深黃色油狀物。
1H NMR(300MHz,CDCl3)δ7.67-7.72(m,4H,ArH),7.18-7.42(m,12H,ArH),7.06(dd,J=2,8Hz,1H,ArH),6.33(t,J=12Hz,1H,CH=CHCO2),5.80(d,J=12Hz,1H,CH=CHCO2),5.67(t,J=9Hz,1H,CH=CCH3),4.90-4.98(m,1H,CHCH=CH),4.78(s,2H,CH2OSi),3.70(s,3H,CO2CH3),2.58-2.64(m,2H,CH2CH),1.98(s,3H,CH=CCH3),1.68(s,4H,CH2CH2),1.27(s,12H,4×CH3),and 1.10(s,9H,SiC(CH3)3).
實(shí)施例27合成(2Z),(6E)-4-[3-(羥甲基)苯基]-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,6-辛二烯酸甲酯(29)在3%濃HCl于甲醇中的溶液中緩慢加熱化合物28(0.70g,1.02mmol)的溶液以溶解該起始物,然后于室溫?cái)嚢?.5h。將反應(yīng)混合物倒入水中并用乙醚萃取。合并有機(jī)層,用飽和氯化鈉溶液洗滌,于無水硫酸鎂上干燥,過濾,并濃縮,得到0.73g黃色液體。經(jīng)柱層析純化(30∶1硅膠/粗產(chǎn)物;用5%-20%乙酸乙酯/己烷梯度洗脫),得到0.34g(74%)化合物29,為黃色透明油狀物。
1H NMR(300MHz,CDCl3)δ7.20-7.34(m,6H,ArH),7.04(dd,J=2,8Hz,1H,7-ArH),6.38(t,J=12Hz,1H,CH=CHCO2),5.81(d,J=12Hz,1H,CH=CHCO2),5.64(t,J=9Hz,1H,CH=CCH3),4.90-4.99(m,1H,CHCH=CH),4.68(d,J=6Hz,2H,CH2OH),3.71(s,3H,CO2CH3),2.64(t,J=6Hz,2H,CH2CH),1.97(s,3H,CH=CCH3),1.66(s,4H,CH2CH2),and 1.26(s,12H,4×CH3).
實(shí)施例28合成(2Z),(6E)-4-[3-甲酰苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,6-辛二烯酸甲酯(30)將MnO2(0.40g,4.6mmol)加至化合物29(0.41g,0.92mmol)的CH2Cl2溶液中,并將所得淤漿于室溫下在塞好的燒瓶中攪拌。于15h、17h、21.5h和23.5h后分別加入MnO2(每次0.40g,4.6mmol)。15h后再加入CH2Cl2(5ml)。39h后,通過1英寸硅藻土塞過濾淤漿,并濃縮濾液,得到0.33g(83%)化合物30,為黃色透明油狀物。
1H NMR(300MHz,CDCl3)δ9.98(s,1H,CHO),7.82(s,1H,4-ArH),7.72(d,J=9Hz,1H,4-ArH),7.58(d,J=9Hz,1H,4-ArH),7.46(t,J=8Hz,1H,4-ArH),7.18(d,J=6Hz,1H,7-ArH),7.19(s,1H,7-ArH),7.02(dd,J=2,8Hz,1H,7-ArH),6.37(t,J=10.5Hz,1H,CH=CHCO2),5.84(d,J=12Hz,1H,CH=CHCO2),5.59(t,J=7.5Hz,1H,CH=CCH3),5.00(q,J=7.5Hz,1H,CHCH=CH),3.69(s,3H,CO2CH3),2.65(t,J=9Hz,2H,CH2CH),1.94(s,3H,CH=CCH3),1.64(s,4H,CH2CH2),and 1.23(s,12H,4×CH3);13C NMR(75MHz,CDCl3)δ192.36(C=O),151.29,144.44,134.24,129.26,128.42,128.32,126.23,123.74,123.47,123.07,119.43,51.25(CO2CH3),43.45,35.15 and 35.03(CH2CH2),34.25,34.01,31.81,30.94,and 16.11;IR(film)2960,2925,2860,1720(ester C=O),1700(CH=O),1455,1435,1215,1195,and 1175cm-1;MS(DCI)m/e 445(MH+).
實(shí)施例29合成(2Z),(6E)-4-[3-甲氧羰基苯基]-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,6-辛二烯酸甲酯(31)向化合物30(0.33g,0.74mmol)-氰化物(0.20g,4.0mmol)和冰醋酸(約0.02ml)的無水醇(12ml)溶液中加入MnO2(0.64g,7.4mmol),并將所得淤漿于室溫下在塞好的燒瓶中攪拌。4h后加入第一份MnO2(0.64g,7.4mmol)。20h后,通過1英寸硅藻土塞過濾反應(yīng)混合物,并濃縮濾液,得到米色固體。用水和乙醚稀釋后倒入分液漏斗。攪動(dòng)分層,用乙醚再次萃取水層。合并有機(jī)相,用飽和氯化鈉溶液洗滌,于無水硫酸鎂上干燥,濃縮后得到0.32g(91%)化合物31,為黃色油狀物。該二酯不經(jīng)純化直接用于下一反應(yīng)。
1H NMR(300MHz,CDCl3)δ7.98(s,1H,4-ArH),7.88(d,J=8Hz,1H,4-ArH),7.50(d,J=8Hz,1H,4-ArH),7.36(t,J=7.5Hz,1H,4-ArH),7.18(d,J=6Hz,1H,7-ArH),7.17(s,1H,7-ArH),7.02(dd,J=2,8Hz,1H,7-ArH),6.38(t,J=11Hz,1H,CH=CHCO2),5.82(d,J=12Hz,1H,CH=CHCO2),5.60(t,J=6Hz,1H,CH=CCH3),4.96(q,J=10.5Hz,1H,CHCH=CH),3.89(s,3H,ArCO2CH3),3.69(s,3H,CO2CH3),2.64(t,J=7.5Hz,2H,CH2CH),1.95(s,3H,CH=CCH3),1.64(s,4H,CH2CH2),and 1.24(s,12H,4×CH3);13C NMR(75MHz,CDCl3)δ167.10(C=O),166.46(C=O),151.61,144.40,143.55,143.43,140.75,136.83,132.70,130.43,128.62,128.45,127.86,126.18,123.76,123.72,123.08,119.17,52.11(CO2CH3),51.21(CO2CH3),43.60,35.21 and 35.18(CH2CH2),35.05,34.24,34.00,31.80(4×CH3),31.93,29.71,16.10,and 15.27;IR(film)2955,2925,2860,1725(C=O),1435,1280,1230,1195,and 1175cm-1;MS(DCI)m/e 475(MH+).
實(shí)施例30合成(2Z),(6E)-4-[3-羧基苯基]-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,6-辛二烯酸(32)將化合物31(0.32g,0.67mmol)和氧化雙(三丁基錫)(1.61g,2.7mmol)的無水甲苯(18ml)溶液于氬氣環(huán)境下回流攪拌11h。該反應(yīng)混合物冷卻至室溫并濃縮除去甲苯。剩余溶液用0.5N HCl溶液(30ml)處理,并用乙酸乙酯(3×40ml)萃取。合并有機(jī)層,用1N NaOH溶液(3×65ml)萃取。合并水層,用1N HCl溶液酸化至PH3。然后用CH2Cl2(3×250ml)萃取。合并有機(jī)層,并濃縮,得到0.24g黃色固體。在C18硅膠上通過逆相柱層析純化(100∶1硅膠/粗產(chǎn)物;用10%H2O甲醇-100%甲醇洗脫),得到0.12g(40%)化合物32,為灰白色固體。
mp 145-148℃;UVmax(CH3OH)249nm(ε=16,500),237nm(ε=22,500);1H NMR(300MHz,CD3OD)δ8.00(s,1H,4-ArH),7.88(d,J=8Hz,1H,4-ArH),7.58(d,J=8Hz,1H,4-ArH),7.42(t,J=7Hz,1H,4-ArH),7.11-7.18(m,2H,7-ArH),6.99(dd,J=2,8Hz,1H,7-ArH),6.47(t,J=11Hz,1H,CH=CHCO2),5.86(d,J=12Hz,1H,CH=CHCO2),5.56(t,J=6Hz,1H,CH=CCH3),4.97(m,1H,CHCH=CH,obscured under CH3OH),2.65(t,J=8Hz,2H,CH2CH),1.94(s,3H,CH=CCH3),1.66(s,4H,CH2CH2),and 1.23(s,12H,4×CH3);13C NMR(75MHz,CD3OD)δ169.58(C=O),152.51,145.36,145.19,144.33,142.38,138.29,133.72,133.60,133.50,130.02,129.88,129.73,129.00,127.24,127.18,124.96,124.84,124.80,124.12,120.74,45.08,36.36,36.24,36.05,35.31,35.15,34.91,32.30,32.21,16.31,and 14.09;IR(KBr)3600-2400(br,CO2H),2960,2925,2860,1695(C=O),1640,1455,1420,1280,and 1245cm-1;MS(DCI)m/e 447(MH+);Anal.Calcd for C29H34O4·0.5H2O:C,76.42;H,7.74.Found:C,76.52;H,7.76.
實(shí)施例31合成(2E)-3-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-丁烯酸乙酯(34)于室溫及氬氣環(huán)境下,用注射滴入的甲醇鈉(25wt%于甲醇,5.5ml,24.0mmol)處理2-乙?;?5,6,7,8-四氫-5,5,8,8-四甲基萘(33,4.60g,20.0mmol)和二乙基膦酰乙酸甲酯(7.33g,34.9mmol)的無水甲苯(80ml)溶液。攪拌反應(yīng)混合物14h,然后倒入裝有乙醚及飽和氯化銨溶液的分液漏斗中。攪動(dòng)分層,有機(jī)層用飽和氯化鈉溶液洗滌,于無水硫酸鎂上干燥。過濾及濃縮后,得到6.5g淺黃色油狀物,經(jīng)柱層析純化(20∶1硅膠/粗產(chǎn)物;用10%乙酸乙酯/己烷洗脫),得到4.10g(72%)化合物34,為無色透明油狀物。
1H NMR(300MHz,CDCl3)δ7.40(d,J=2Hz,1H,ArH),7.30(d,J=7Hz,1H,ArH),7.25(dd,J=2,8Hz,1H,ArH),6.15(brs,1H,C=CH),3.75(s,3H,CO2CH3),2.58(s,3H,CH3C=C),1.67(s,4H,CH2CH2),1.26(s,6H,2×CH3),and 1.28(s,6H,2×CH3).
實(shí)施例32合成(2E)-3-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-丁烯醇(35)于0℃及氬氣環(huán)境下,在10min向氫化鋁鋰(0.33g,8.6mmol)的乙醚(100ml)淤漿中加入酯34(4.10g,14.3mmol)的無水乙醚(40ml)溶液。2h后再加入另一份氫化鋁鋰(0.13g,3.4mmol),并將混合物攪拌5h。通過依次加入H2O(0.46ml)、15%氫氧化鈉水溶液(0.46ml)和H2O(1.38ml)終止反應(yīng)。過濾所得淤漿,真空濃縮濾液,得到3.8g無色油狀物。經(jīng)柱層析純化(30∶1硅膠/粗產(chǎn)物;用10%-15%乙酸乙酯/己烷洗脫)后,得到3.51g(95%)化合物35,為無色油狀物。
1H NMR(300MHz,CDCl3)δ7.35(d,J=2Hz,1H,ArH),7.28(d,J=8Hz,1H,ArH),7.18(dd,J=2,8Hz,1H,ArH),5.95(t,J=5Hz,1H,C=CH),4.35(t,J=5Hz,2H,CH2OH),2.10(s,3H,CH3C=C),1.65(s,4H,CH2CH2),1.30(s,6H,2×CH3),and 1.28(s,6H,2×CH3).
實(shí)施例33合成(2E)-3-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-丁烯基溴(36)于氬氣環(huán)境下,將三溴化磷(0.31g,1.16mmol)和吡啶(0.057g,0.72mmol)于石油醚(18ml)中的攪拌溶液冷卻至-10℃。用化合物35(0.94g,3.62mmol)的無水乙醚(18ml)溶液處理該混合物。在2.5h內(nèi)溫?zé)嶂潦覝睾笥靡颐严♂?,并用水洗滌兩次。合并水層,用另一份乙醚反萃取。合并有機(jī)層,用飽和氯化鈉溶液洗滌,于無水硫酸鎂上干燥,過濾并濃縮,得到1.00g(86%)化合物36,為灰白色固體。該溴化物不經(jīng)純化直接用于下一反應(yīng)。
1H NMR(300MHz,CDCl3)δ7.33(d,1H,ArH),7.28(d,1H,ArH),7.18(dd,J=12Hz,1H,ArH),6.05(t,J=9Hz,1H,C=CH),4.12(d,J=9Hz,2H,CH2Br),2.13(s,3H,CH=CCH3),1.68(s,4H,CH2CH2),1.26(s,6H,2×CH3),and 1.24(s,6H,2×CH3).
實(shí)施例34合成(Z)-2-(3-三氟甲苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-戊烯基乙酸酯(37)于室溫及氬氣環(huán)境下,用4-二甲基氨基吡啶(0.01g)和乙酸酐(0.32g,3.1mmol)處理(Z)-2-(3-三氟甲苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-戊烯醇5r(0.99g,2.4mmol)的無水吡啶(25ml)溶液。攪拌該混合物2h后,在乙醚(100ml)和1N HCl溶液(50ml)之間分配。醚層進(jìn)一步用飽和氯化鈉溶液洗滌,于無水硫酸鎂上干燥,過濾并濃縮,得到1.09g(100%)無色油狀產(chǎn)物。該乙酸酯不經(jīng)純化直接用于下一反應(yīng)。
1H NMR(300MHz,CDCl3)δ7.50(d,J=8Hz,1H,2-ArH),7.36-7.41(m,2H,2-ArH),7.17(d,J=8Hz,1H,2-ArH),7.11(d,J=8Hz,1H,5-ArH),6.98(d,J=2Hz,1H,5-ArH),6.82(dd,J=2,8Hz,1Hz,5-ArH),5.89(t,J=7.5Hz,1H,C=CH),4.73(s,2H,CH2OAc),2.61(t,J=7Hz,2H,ArCH2),2.24(q,J=7Hz,2H,ArCH2CH2),1.99(s,3H,CH3C=O),1.64(s,4H,CH2CH2),1.24(s,6H,2×CH3),and 1.22(s,6H,2×CH3);13C NMR(75MHz,CDCl3)δ170.66(C=O),144.70,142.52,138.81,137.91,134.89,133.09,131.95,128.67,126.48,126.45,125.73,125.36,125.31,124.02,68.68(CH2OAc),35.33,35.14,35.09,34.12,31.87,31.81,30.67,and 20.89;IR(film)2960,2925,2860,1745(C=O),1325,1225,1165,and 1130cm-1;MS(DCI)m/e 399(M+-OAc).
實(shí)施例35合成(Z)-2-甲氧羰基-4-(3-三氟甲苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-4-庚烯酸甲酯(38)于室溫及氬氣環(huán)境下,將丙二酸二甲酯(1.44g,10.9mmol)滴加至氫化鈉(80%分散于油中,0.31g,10.5mmol)的無水THF(20ml)淤漿中。攪拌15min后用(Z)-2-(3-三氟甲苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2-戊烯基乙酸酯(37)(1.09g,2.38mmol)、三苯膦(0.062g,0.24mmol)和四(三苯膦)鈀(O)(0.137g,0.12mmol)的THF(4ml)溶液處理。所得混合物回流加熱4h。冷卻至室溫后在乙醚和飽和氯化銨溶液之間分配。用飽和氯化鈉溶液洗滌有機(jī)相,于無水硫酸鎂上干燥,過濾,并濃縮,得到1.68g粗產(chǎn)物。經(jīng)柱層析純化(30∶1硅膠/粗產(chǎn)物;用2%-4%乙酸乙酯的己烷洗脫,每級(jí)分25ml)。收集級(jí)分8-21(Rf=0.25,10%乙酸乙酯/己烷)并濃縮,得到0.65g無色油狀物。NMR顯示存在10%其它異構(gòu)體。收集級(jí)分22-30(Rf=0.25,10%乙酸乙酯/己烷)并濃縮,得到0.41g無色油狀物。NMR顯示存在98%以上的一種異構(gòu)體(Z)-2-甲氧羰基-4-(3-三氟甲苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-4-庚烯酸甲酯(38)。該反應(yīng)的合并產(chǎn)率為84%。
1H NMR(300MHz,CDCl3)δ7.33-7.51(m,3H,4-ArH),7.10-7.23(m,2H,1×4-ArH and 1×7-ArH),6.95(d,J=2Hz,1H,7-ArH),6.79(dd,J=2,8Hz,1H,7-ArH),5.65(t,J=7Hz,1H,C=CH),3.64(s,6H,2×CO2CH3),3.31(t,J=8Hz,1H,HC(CO2Me)2),2.92(d,J=8Hz,2H,CH2CH(CO2Me)2),2.53(t,J=7Hz,2H,ArCH2),2.13(q,J=7Hz,2H,ArCH2CH2),1.63(s,4H,CH2CH2),1.23(s,6H,2×CH3),and 1.21(s,6H,2×CH3);13C NMR(75MHz,CDCl3)δ169.17(C=O),144.69,142.41,140.17,138.07,136.01,132.02,131.17,128.76,126.41,126.32,125.60,125.25,123.86,52.45(CO2CH3),50.60(C(CO2Me)2),38.16,35.65,35.15,35.09,34.12,33.92,31.87,31.80,and 30.80;IR(film)2960,2925,2860,1755(C=O),1740(C=O),1435,1325,1310,1275,1235,1160,1130,and 1070cm-1;MS(DCI)m/e 531(MH+),499(M+-CH3O).
實(shí)施例36合成(Z)-2-羧基-4-(3-三氟甲苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-4-庚烯酸(39)將(Z)-2-甲氧羰基-4-(3-三氟甲苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-4-庚烯酸甲酯(38)(0.15g,0.28mmol)于1∶1∶1甲醇/THF/2N氫氧化鈉溶液(4.5ml)中的溶液加熱回流4h。冷卻至室溫后用10%鹽酸溶液(10ml)處理。用乙醚(2×50ml)萃取水溶液,并用飽和氯化鈉溶液洗滌有機(jī)層,于無水硫酸鎂上干燥,過濾并濃縮,得到0.13g(92%)白色泡沫。
1H NMR(300MHz,CDCl3)δ7.48(d,J=8Hz,1H,4-ArH),7.37(d,J=8Hz,1H,4-ArH),7.32(brs,1H,4-ArH),7.09-7.20(m,2H,1×4-ArH and 1×7-ArH),6.94(d,J=2Hz,1H,7-ArH),6.77(dd,J=2,8Hz,1H,7-ArH),5.68(t,J=7.5Hz,1H,C=CH),3.36(t,J=8Hz,1H,CH(CO2Me)2),2.94(d,J=8Hz,2H,CH2CH(CO2Me)2),2.53(t,J=7Hz,2H,ArCH2),2.14(q,J=7Hz,2H,ArCH2CH2),1.63(s,4H,CH2CH2),1.22(s,6H,2×CH3),and 1.20(s,6H,2×CH3);13C NMR(75MHz,CDCl3)δ173.50(C=O),144.72,142.46,139.80,138.06,135.35,132.10,131.72,128.83,126.37,125.73,125.22,124.06,50.14(C(CO2Me)2),37.97,35.49,35.15,35.09,34.10,33.92,31.86,31.80,and 30.86;IR(KBr)2400-3600(br),1720(C=O),1460,1440,1410,1325,1310,1165,1130,and 1070cm-1;MS(FAB)m/e 525(M++Na);Anal.Calcd for C29H33O4F3·0.25H2O:C,68.69;H,6.66.Found:C,68.73;H,6.68.
實(shí)施例37合成(Z)-4-(3-三氟甲苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-4-庚烯酸(40)用氧化銅(Ⅰ)(0.003g,0.02mmol)處理(Z)-2-羧基-4-(3-三氟甲苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-4-庚烯酸(39)(0.108g,0.21mmol)的無水乙腈(2ml)溶液。回流加熱混合物7h,再加入氧化銅(Ⅰ)(0.003g,0.02mmol),繼續(xù)加熱14h,然后冷卻至室溫,并真空濃縮。殘余物用水(5ml)和10%鹽酸溶液(5ml)處理。水溶性混合物用乙醚萃取(2×50ml),有機(jī)層用飽和氯化鈉溶液洗滌,于無水硫酸鎂上干燥,過濾并濃縮,得到0.10g粗產(chǎn)物。柱層析(60∶1硅膠/粗產(chǎn)物;用30%乙酸乙酯/己烷)后,得到0.057g(58%)無色油狀產(chǎn)物。
1H NMR(300MHz,CDCl3)δ7.47(d,J=8Hz,1H,4-ArH),7.37(d,J=8Hz,1H,4-ArH),7.32(brs,1H,4-ArH),7.16(d,J=8Hz,1H,4-ArH),7.08(d,J=8Hz,1H,7-ArH),6.97(d,J=2Hz,1H,7-ArH),6.80(dd,J=2,8Hz,1H,7-ArH),5.61(t,J=7.5Hz,1H,C=CH),2.64(t,J=7.5Hz,2H,CH2CO2),2.56(t,J=7.5Hz,2H,ArCH2),2.33(t,J=7.5Hz,2H,C=CCH2CH2CO2),2.15(q,J=7.5Hz,2H,ArCH2CH2),1.65(s,4H,CH2CH2),1.24(s,6H,2×CH3),and 1.22(s,6H,2×CH3);13C NMR(75MHz,CDCl3)δ178.61(C=O),144.63,142.39,140.94,138.24,138.13,131.86,129.01,128.68,126.54,126.40,125.85,125.73,125.05,123.63,35.73,35.17,35.11,34.12,33.93,33.85,32.80,31.88,31.82,and 30.85;IR(film)3600-2400(br),2960,2925,2860,1710(C=O),1495,1455,1440,1410,1325,1310,1275,1165,1130,and 1070cm-1;MS(FAB)m/e 481(MH+);Anal.Calcd for C28H33O2F3·0.25H2O:C,72.62;H,7.29.Found:C,72.51;H,7.16.
在不超出本發(fā)明范圍的情況下,可作出如本領(lǐng)域熟練技術(shù)人員所能預(yù)先的合理改動(dòng)。
權(quán)利要求
1.式Ⅰ化合物 其中C2和C3之間和/或C4和C5之間的鍵為不飽和鍵;X=COOH、H、F、Cl、Br、I、COOR″、CONH2、COR′″、CHO、CH2OH、CH2OR′″、OH、OR′″、CF3、C1-6烷基、C1-6鏈烯基、C1-6鹵代烷基、NO2、P(O)(OH)2、SO2H或SO3H;R=取代或未取代烷基、芳基、芳烷基、鏈烯基或芳烯基,條件是每一基團(tuán)有6個(gè)或6個(gè)以上(優(yōu)選6-30)碳原子,且R不為 R′=H或C1-6烷基;R″=H、C1-6烷基、C(R3)2OC(O)R4、CH2CH2NR5R6、CH2CH2CH2NR5R6、CH2C(O)N(R6)2或其它產(chǎn)生生理上可水解的酯的基團(tuán);R′″=C1-6烷基;R3=H、CH3、C2H5、CH3CH2CH2(R3相同或不同);R4=C6-12芳基、C1-7直鏈、支鏈或環(huán)烷基、C1-7直鏈、支鏈或環(huán)烷氧基;R5=R6,或當(dāng)與R6相連時(shí)為C3-C6環(huán)烷基或-CH2CH2OCH2CH2-基團(tuán);R6=C1-3烷基。
2.權(quán)利要求1的化合物,它具有選自IA、IB、IC或ID類型的結(jié)構(gòu)
3.權(quán)利要求2的化合物,它符合結(jié)構(gòu)式IA。
4.權(quán)利要求3的化合物,它選自(2Z),(4Z)-4-(3-羧基苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-戊二烯酸;(2Z),(4Z)-4-(3-羧基苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2,4-戊二烯酸;(2Z),(4Z)-4-(3-羧基苯基)-5-(癸氧苯基)-2,4-戊二烯酸;(2Z),(4Z)-4-(3-羧基苯基)-5-(3,4-雙癸氧苯基)-2,4-戊二烯酸;(2Z),(4Z)-4-(3-羧基苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸;(2Z),(4Z),(6E)-4-(3-羧基苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4,6-辛三烯酸;(2Z),(4Z)-4-(3-羧苯基)-7-[4-(1-金剛烷基)-3-甲氧苯基]-2,4-庚二烯酸;(2Z),(4Z)-4-(3-羧苯基)-7-[3-(1-金剛烷基)-4-甲氧苯基]-2,4-庚二烯酸;(2Z),(4Z)-4-(3-三氟甲苯基)-5-(4-癸氧苯基]-2,4-戊二烯酸;(2Z),(4Z)-4-(3-三氟甲苯基)-5-(3-癸氧苯基)-2,4-戊二烯酸;(2Z),(4Z)-4-(3-三氟甲苯基)-5-(2-癸氧苯基)-2,4-戊二烯酸;(2Z),(4Z)-4-(3-三氟甲苯基)-5-[4-(2E),(6E)-3,7-二甲基辛-2,6-二烯氧]苯基-2,4-戊二烯酸;(2Z),(4Z)-4-(3-三氟甲苯基)-5-(3,4-雙癸氧苯基)-2,4-戊二烯酸;(2E),(4Z)-4-(3-三氟甲苯基)-5-(3,4-雙癸氧苯基)-2,4-戊二烯酸;(2Z),(4Z)-4-(3-三氟甲苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2,4-戊二烯酸;(2Z),(4Z)-4-(3-三氟甲苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸;(2Z),(4Z)-4-(4-氟苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸;(2Z),(4Z)-4-(3-氟苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸;(2Z),(4Z)-4-苯基-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸;(2Z),(4Z)-4-(3-三氟甲苯基)-7-[3-(1-金剛烷基)-4-甲氧苯基]-2,4-庚二烯酸;(2Z),(4Z)-4-苯基-7-[3-(1-金剛烷基)-4-甲氧苯基]-2,4-庚二烯酸;(2Z),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-甲氧苯基]-2,4-庚二烯酸;(2Z),(4Z)-4-苯基-7-[4-(1-金剛烷基)-3-甲氧苯基]-2,4-庚二烯酸;(2Z),(4Z)-4-(3-三氟甲苯基)-7-[2-(1-金剛烷基)-4-甲氧苯基]-2,4-庚二烯酸;(2Z),(4Z)-4-(3-三氟甲苯基)-5-[4-(1-金剛烷基)-3-甲氧苯基]-2,4-戊二烯酸;(2Z),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-羥基苯基]-2,4-庚二烯酸;(2Z),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-戊氧苯基]-2,4-庚二烯酸;(2Z),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-(4-甲氧芐氧基)苯基]-2,4-庚二烯酸;(2Z),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-芐氧基)苯基]-2,4-庚二烯酸;(2Z),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-(羧基甲氧基)苯基]-2,4-庚二烯酸和(2Z),(4Z)-3-甲基-4-(3-羧基苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2,4-戊二烯酸;
5.權(quán)利要求2的化合物,它符合結(jié)構(gòu)式IB。
6.權(quán)利要求5的化合物,它選自(2E),(4Z)-4-(3-羧苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2,4-戊二烯酸;(2E),(4Z)-4-(3-羧基苯基)-5-(3,4-雙戊氧苯基)-2,4-戊二烯酸;(2E),(4Z)-4-(3-羧基苯基)-5-(3,4-雙癸氧苯基)-2,4-戊二烯酸;(2E),(4Z)-4-(3-羧基苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸;(2E),(4Z)-4-(3-三氟甲苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸;(2E),(4Z)-4-(4-氟苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸;(2E),(4Z)-4-(3-氟苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸;(2E),(4Z)-4-苯基-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,4-庚二烯酸;(2E),(4Z)-4-(3-三氟甲苯基)-7-[3-(1-金剛烷基)-4-甲氧苯基]-2,4-庚二烯酸;和(2E),(4Z)-4-(3-三氟甲苯基)-7-[4-(1-金剛烷基)-3-甲氧苯基]-2,4-庚二烯酸;
7.權(quán)利要求2的化合物,它符合結(jié)構(gòu)式IC。
8.權(quán)利要求7的化合物,它選自(2E),(6E)-4-(3-羧基苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-2,6-辛二烯酸,和(2E)-4-[3-羧苯基]-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-庚二烯酸。
9.權(quán)利要求2的化合物,它符合結(jié)構(gòu)式ID。
10.(Z)-4-(3-三氟甲苯基)-7-(5,6,7,8-四氫-5,5,8,8-四甲基-2-萘基)-4-庚烯酸。
11.權(quán)利要求1化合物的鉀、鈉、三乙醇胺、三(羥甲基)氨基甲烷、N-甲基葡糖胺或L-賴氨酸單鹽,其中R″=H。
12.權(quán)利要求1化合物的鉀、鈉、三乙醇胺、三(羥甲基)氨基甲烷、N-甲基葡糖胺、或L-賴氨酸二鹽,其中R″=H,X=COOH。
13.(2Z),(4Z)-3-甲基-4-(3-羧苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2,4-戊二烯酸的二鉀鹽。
14.(2Z),(4Z)-3-甲基-4-(3-羧苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2,4-戊二烯酸的二鈉鹽。
15.(2Z),(4Z)-3-甲基-4-(3-羧苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2,4-戊二烯酸的二(三乙醇胺)鹽。
16.(2Z),(4Z)-3-甲基-4-(3-羧苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2,4-戊二烯酸雙[三(羥甲基)氨基甲烷]鹽。
17.(2Z),(4Z)-3-甲基-4-(3-羧苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2,4-戊二烯酸的雙(N-甲基葡糖胺)鹽。
18.(2Z),(4Z)-3-甲基-4-(3-羧苯基)-5-(5,6,7,8-四氫-5,5,8,8-四甲基-2-蒽基)-2,4-戊二烯酸的雙(L-賴氨酸)鹽。
19.制備結(jié)構(gòu)式IA化合物的方法,它包括以下步驟
20.一種藥物組合物,它含有消炎有效量的至少一種權(quán)利要求1的化合物和適當(dāng)量的至少一種藥用載體。
21.權(quán)利要求20的組合物,其中權(quán)利要求1化合物的含量為約0.005-10.0wt%。
22.權(quán)利要求21的組合物,它為表面劑量形式。
23.權(quán)利要求21的組合物,它為口服劑量形式。
24.治療炎癥的方法,它包括給患者服用消炎有效量的權(quán)利要求1化合物。
25.治療炎癥的方法,它包括給患者服用消炎有效量的權(quán)利要求2化合物。
26.權(quán)利要求25的方法,其中化合物是通過表面配方給藥。
27.權(quán)利要求25的方法,其中化合物是通過口服配方給藥。
全文摘要
本發(fā)明涉及一類新的脂環(huán)族化合物,它們是磷脂酶A
文檔編號(hào)C07C219/10GK1099380SQ94106460
公開日1995年3月1日 申請(qǐng)日期1994年6月15日 優(yōu)先權(quán)日1993年6月16日
發(fā)明者J·J·布朗森, F·I·卡羅爾, K·M·格林, A·盧因, M·M·曼蘇里, S·V·丹德里 申請(qǐng)人:布里斯托爾-米爾斯·斯奎布公司