单刀根活性成分的研究及菲骈吲哚里西啶类生物碱手性全合成的初步研究
摘要
单刀根为豆科仪花属植物仪花(Lysidicie rhodostegia Hance)的根，分布于我国广西、广东、云南、贵州、台湾等地，资源丰富，为我国民间传统用药，主要用于治疗跌打损伤，风湿骨痛等症。该属植物的化学成分及药理活性的研究未见文献报道。
为寻找新型的作用于心脑血管的活性成分，我们采用活性跟踪的方法，利用现代色谱分离技术对单刀根的化学成分进行了较系统研究，从其乙酸乙酯和正丁醇部位中分离得到34个化合物，利用波谱和化学方法对分离得到的化合物进行了结构测定和鉴定，分别为仪花苷A(lysidiside A，1)、仪花苷B(lysidisideB，2)、仪花苷C(lysidiside C，3)、仪花苷D(lysidiside D，4)、mopanolchin(5)、7-O-mopanol-β-D-glucopyranoside(6)、(反)-4'，5-二羟基—二苯乙烯-3-O-[α-L-吡喃鼠李糖基]-(1→2)-β-D-木糖苷(E-4'，5-dihydroxy-stilbene-3-O-[α-L-rhamnopyranosyl]-(1→2)-β-D-xylcopyranoside，7)、(顺)-4'，5-二羟基—二苯乙烯-3-O-[α-L-吡喃鼠李糖基]-(1→2)-β-D-木糖苷(Z-4'，5-dihydroxy-stilbene-3-O--[α-L-rhamnopyranosyl]-(1→2)-β-D-xylcopyranoside，8)、2R，3R-表儿茶素-3-3'，5'-二甲氧基-没食子酸酯(2R，3R-epicatichin-3-3'，5'-di-methoxy-gallate，9)、仪花苷A_2(lysidiside A_2，10)、3'-甲基丁酰基-间苯三酚(3'-methylbutyryl-phloroglucinol 11)、虎杖苷(polydatin，12)、白藜芦醇-3-O-β-D-吡喃木糖苷(E-resveratrol-3-O-β-D-xylopyranoside，13)、白藜芦醇(resveratrol，14)、(-)-5'-methoxyisolariciresinol 3α-O-β-D-glucopyranoside(15)、(+)-5'-methoxyisolariciresinol 3α-O-β-D-glucopyranoside(16)、(-)-lyoniresinol 3α-O-β-D-glucopyranoside(17)、(+)mopanol(18)、(-)-epicatechin-3-O-gallte(19)、表儿茶素(epicatechin 20)、柚皮素(naringenin 21)、北美圣草素(eriodictyol 22)、木犀草素(luteolin 23)、3'，4'，7-三羟基黄酮(3'，4'，7-trihydroxyflavone 24)、(-)-robinetinidol(25)、羽扇豆醇(lupeol 26)、2-羟基羽扇豆醇(2-hydroxy-lupeol 27)、白桦酸(betulinic acid 28)、sitosteryl3β-glucoside 6'-O-palmitate(29)、二十一羧酸-3-谷甾醇酯(heneicosanic-3-O-β-sitosterolate 30)、胡萝卜苷(daucosterol 31)、β-谷甾醇(β-sitosterol 32)、没食子酸(gallic acid 33)和棕榈酸(palmitic acid 34)。其中化合物1～9为新化合物，化合物10为人工产物，其他化合物均为首次从该属植物中分离得到。
上述化合物分属不同的结构类型，包括间苯三酚、二苯乙烯、木脂素糖苷、黄酮、三萜等。利用内皮依赖性血管舒张剂模型对分离得到的化合物进行了活性筛选，筛选结果表明化合物1、2、3、6、11、12、13、18能在L-硝基精氨酸(NOS inhibitor)和吲哚美辛(COX inhibitor)的存在下使得乙酰胆碱对大鼠动脉血管扩张恢复到正常水平，因此具有类似NO的扩张血管活性。量效关系研究表明，化合物11在高、中、低剂量时均能使得乙酰胆碱的扩血管活性恢复到正常水平，因此值得进行治疗内皮功能障碍的深入研究。
论文同时对分离得到的化合物进行了抗氧化活性的筛选，抗氧化试验结果表明11、14、18、19、20具有较好的抗氧化活性，高、中、低浓度时其活性与阳性对照维生素E相当。
论文中分到四个间苯三酚类苷及其苷元，为此我们对间苯三酚类化合物的结构、生源及生物合成、生物活性和波谱特征进行了综述。
菲骈吲哚里西丁类生物碱是萝摩科娃儿藤属植物中主要生物碱成分，该类化合物被证明具有抗肿瘤活性，本试验室从三分丹和卵叶娃儿藤中分离得到的新天然产物(+)-13a-去氧娃儿藤宁(Deoxytylophorinine CAT-1)经药理筛选具有较强的抗肿瘤活性。本论文对化合物CAT-1进行了手性全合成的探索。利用对甲氧基苯甲醛与3，4-二甲氧基苯乙酸经Perking缩合得到(E)-2-(3，4-二甲氧苯基)-3-(4-甲氧苯基)-2-丙烯酸，该酸甲酯化后经Diels-Alder反应生成菲环结构3，6，7-三甲氧基-9-菲酸甲酯，该酯经还原胺化生成1-[3，6，7-三甲氧基-9-菲甲基]-四氢-2-吡咯酸甲酯，引入手性含氮五元环，再经还原生成β-胺基醇取代的菲环化合物[1-(3，6，7-三甲氧基-9-菲基)-甲基]-四氢-2-吡咯醇，该醇进行分子内傅克烷基化反应，试图得到手性保持的飞骈吲哚里西啶类骨架的产物，未能成功。
同时设计了进行了β-胺基醇取代二苯乙烯进行分子内亲核取代反应，试图得到手性保持的沙普溶型生物碱，再Diels-Alder反应构建菲骈吲哚里西啶类骨架。本路线采用对甲氧基苯甲醛和3，4-二甲氧基苯乙酸缩合得到(E)-2-(3，4-二甲氧苯基)-3-(4-甲氧苯基)-2-丙烯酸，该酸经酰氯与手性氨基酸(L-脯氨酸甲酯)反应，得到1-[(顺)-2-(3，4-二甲氧-苯基)-3-(4-甲氧-苯基)-2-丙烯酰基]-2-吡咯酸甲酯。产物经还原后得到1-[(顺)-2-(3，4-二甲氧-苯基)-3-(4-甲氧-苯基)-2-丙烯酰基]四氢-2-吡咯烷醇，将该醇的氮原子氧化后与甲磺酰氯反应生成相应的甲磺甲磺酸酯。论文试图由该酯在碱性条件下实现关环，得到菲骈吲哚里西啶类骨架，但未能成功。论文同时也用1-[(顺)-2-(3，4-二甲氧-苯基)-3-(4-甲氧-苯基)-2-丙烯酰基]四氢-2-吡咯烷醇进行了傅克反应，试图关环，未能成功。
在试验过程中得到由1-[(顺)-2-(3，4-二甲氧-苯基)-3-(4-甲氧-苯基)-2-丙烯酰基]四氢-2-吡咯烷醇进行甲磺酰化时未能得到相应的甲磺酰酯，而是得到羟基被氯代的产物2-氯甲基1-[(顺)-2-(3，4-二甲氧-苯基)-3-(4-甲氧-苯基)-2-丙烯酰基]四氢-2-吡咯烷，该氯代物在NaH／DMF条件下反应，得到N，N-二甲基-1-[(顺)-2-(3，4-二甲氧-苯基)-3-(4-甲氧-苯基)-2-丙烯酰基]-甲氨
Lysidice rhodostega Hance is a traditional medicine used in China for the treatment of trauma, acesodyne and fractures by local folks for long time. The plant is widely distributed in Guangxi, Guangdong, Yunnan, Guizhou and Taiwan provinces of China. To our knowledge, no phytochemical investigation about this plant has been described in literature up to now.Bioassay-directed separation of the ethanol extract of the roots of the title plant led to the isolation of ten new compounds l-10(compound 10 is artificial) and twenty-four known ones 11-34. On the basis of chemical and spectra analysises, these compounds were elucidated as lysidiside A (1), lysidiside B (2). lysidiside C (3) lysidiside D(4), mopanolchin (5), 7-O-mopanol-β-D-glucopyranoside (6), E-4',5-di-hydroxystilbene-3-O-[α-L-rhamnopyranosyl]-(1→2)-β-D-xylcopyranoside, (7) Z-4',5-dihydroxy-stilbene-3-O-[α-L-rhamnopyranosyl]-(1→2)-β-D-xylcopyranoside (8) 2R, 3R-epicatichin-3-3',5'-dimethoxy-gallate (9)n lysidiside A_2(10), 1-β-methylbutyryl) phloroglucinol (11), polydatin (12), E-resveratrol-3-O-β-D-xylopyranoside (13), resveratrol (14), (-)-5'-methoxyisolariciresinol 3α-O-β-D-glucopyranoside (15), (+)-5'-methoxyisolari-ciresinol-3α-O-β-D-glucopyranoside (16), (-)-lyoniresinol 3α-O-β-D-glucopyranoside (17), (+) mopanol (18), (-)-epicatechin -3-O- gallte (19), cpicatechin (20), naringenin (21), eriodictyol (22), luteolin (23), 3',4',7-trihydroxyflavone (24), (-)-robinetinidol (25), lupeol (26), 2-hydroxyl-lupeol (27), betulinic acid (28), sitosteryl 3β-glucoside 6'-O-palmitate (29), heneicosanic-3-O-β-sitosterolate (30), daucosterol (31),β-sitosterol (32), gallic acid (33) and palmitic acid (34). All of these compounds were isolated from the title plant for the first time.The Endothelium-dependent vasodilation of the isolated compounds were investigated. It was found that compound 1, 2, 3, 6, 11, 12, 13, 18 inhibited phenylepherine -induced vasoconstriction in the rat aortic rings in the presences of Indomethacin (COX inhibitor ) and N~ω-L-nitro-arginine (NOS inhibitor). Compound 11 was proved to be active at low, middle and high concentrations, which mean the compound was worthy of being further investigated for the treatment of endothelium malfunction.
Furthermo re, antioxyside activities of the isolated compounds were also investigated. It was showed that the inhibitor abilities of compounds 11, 14, 18, 19, 20 were almost equivalent as those of the positive control agent vitamin E at high, middile and low concentrations.
Four phloroglucinol glycosides and their aglycone had been isolated from this plant so that we reviewed the structures, bioresouces, biosynthesis, bioactivity and spectral character of this kind of compounds.
Phenanthroindolizidine alkaloids, which were the main alkaloid constituents of Tylophora, were proved to be cytotoxic. The new cytotoxic natural product deoxytylophorinine (CAT-1) was isolated from Tylophora overta by our group for the first time.
In this paper, the primary chiral total synthesis of the CAT-1 has been studied. Compound (E)-2-(3, 4-dimethoxyphenyl)-3-(4-methoxyphenyl)-2-propenoic acid, synthesized from 2-(3, 4-dimethoxyphenyl)-acetic acid and 4-methoxybenzaldehyde by Perking reaction, was methylated and than reducted to the corresponding alcohol. The alcohol was oxidated to afford the corresponding aldehyde. Compound 1-[(3, 6, 7 -trimethxyl-4b, 10-dihydro-9-phenathrenyl-methyl)-2-pyrrolidine carboxylate was later synthesized by N-deprotection-reduction form the above aldehyde and L- proline methl ester. The corresponding pyrrolidine carboxylate was further reducted to 1-[3, 6, 7-trimethoxy-9-phenanthryl]-tetrahydro-2-pyrrolyl]-methanol. Friedel- -Crafts reaction was used in order to obtain the asymmetric deoxytylophorinine form the above methanolic ramification but failed.
Another scheme was designed for deoxytylophorinine form chiral septicine by Diels-Alder reaction. In this scheme, compound methyl-1-[(E)-2-(3, 4-dimethoxyl- -phenyl)-3-(4-methoxylphenyl)-2-propenoyl]-2-pyrrolidine carboxylate, which was obtained from (E)-2-(3, 4-dimethoxyphenyl)-3-(4-methoxyphenyl)-2-pro- -penoic acid and L-proline methl ester, was designed. This carboxylate was than reducted to amino alcohol 1-[(E)-2-(3, 4-dimethoxyl phenyl)-3-(4-methoxylphenyl)- 2-propenoyl]-tetrahydro-2-pyrrolyl methanol. The amino alcohol was oxidated to N-oxide compound and further mesylated by methanesulfonyl chloride to afford the corresponding mesylate. We want to get chiral septicine alkaloid under base conditions from this mesylate but failed. The septicine alkaloid could not be synthesized using Friedel-crafts reaction from the amino alcohol or its N-oxide compound ether.
An unexpected compound 2-chloromethyl-1-[(E)-2-(3, 4-dimethoxylphenyl)-3- (4-methoxyl-phenyl)-2-propenoyl]-pyrrolidine was obtained during the mesylated by methanesulfonyl chloride from the 1-[(E)-2-(3, 4-dimethoxyl phenyl)-3-(4-methoxyl- -phenyl)-2-propenoyl]-tetrahydro-2-pyrrolyl methanol under standard mesylated conditions. To our surprise, this halide was tansported to N, N-dimethyl-1-[(E)-2-(3, 4- dimethoxyl-phenyl)-3-(4-methoxylphenyl)-2-propenoyl]-tetrahydro-2-pyrrolylmethane -mine in the presences of sodium hydride and anhydrous DMF.
为寻找新型的作用于心脑血管的活性成分，我们采用活性跟踪的方法，利用现代色谱分离技术对单刀根的化学成分进行了较系统研究，从其乙酸乙酯和正丁醇部位中分离得到34个化合物，利用波谱和化学方法对分离得到的化合物进行了结构测定和鉴定，分别为仪花苷A(lysidiside A，1)、仪花苷B(lysidisideB，2)、仪花苷C(lysidiside C，3)、仪花苷D(lysidiside D，4)、mopanolchin(5)、7-O-mopanol-β-D-glucopyranoside(6)、(反)-4'，5-二羟基—二苯乙烯-3-O-[α-L-吡喃鼠李糖基]-(1→2)-β-D-木糖苷(E-4'，5-dihydroxy-stilbene-3-O-[α-L-rhamnopyranosyl]-(1→2)-β-D-xylcopyranoside，7)、(顺)-4'，5-二羟基—二苯乙烯-3-O-[α-L-吡喃鼠李糖基]-(1→2)-β-D-木糖苷(Z-4'，5-dihydroxy-stilbene-3-O--[α-L-rhamnopyranosyl]-(1→2)-β-D-xylcopyranoside，8)、2R，3R-表儿茶素-3-3'，5'-二甲氧基-没食子酸酯(2R，3R-epicatichin-3-3'，5'-di-methoxy-gallate，9)、仪花苷A_2(lysidiside A_2，10)、3'-甲基丁酰基-间苯三酚(3'-methylbutyryl-phloroglucinol 11)、虎杖苷(polydatin，12)、白藜芦醇-3-O-β-D-吡喃木糖苷(E-resveratrol-3-O-β-D-xylopyranoside，13)、白藜芦醇(resveratrol，14)、(-)-5'-methoxyisolariciresinol 3α-O-β-D-glucopyranoside(15)、(+)-5'-methoxyisolariciresinol 3α-O-β-D-glucopyranoside(16)、(-)-lyoniresinol 3α-O-β-D-glucopyranoside(17)、(+)mopanol(18)、(-)-epicatechin-3-O-gallte(19)、表儿茶素(epicatechin 20)、柚皮素(naringenin 21)、北美圣草素(eriodictyol 22)、木犀草素(luteolin 23)、3'，4'，7-三羟基黄酮(3'，4'，7-trihydroxyflavone 24)、(-)-robinetinidol(25)、羽扇豆醇(lupeol 26)、2-羟基羽扇豆醇(2-hydroxy-lupeol 27)、白桦酸(betulinic acid 28)、sitosteryl3β-glucoside 6'-O-palmitate(29)、二十一羧酸-3-谷甾醇酯(heneicosanic-3-O-β-sitosterolate 30)、胡萝卜苷(daucosterol 31)、β-谷甾醇(β-sitosterol 32)、没食子酸(gallic acid 33)和棕榈酸(palmitic acid 34)。其中化合物1～9为新化合物，化合物10为人工产物，其他化合物均为首次从该属植物中分离得到。
上述化合物分属不同的结构类型，包括间苯三酚、二苯乙烯、木脂素糖苷、黄酮、三萜等。利用内皮依赖性血管舒张剂模型对分离得到的化合物进行了活性筛选，筛选结果表明化合物1、2、3、6、11、12、13、18能在L-硝基精氨酸(NOS inhibitor)和吲哚美辛(COX inhibitor)的存在下使得乙酰胆碱对大鼠动脉血管扩张恢复到正常水平，因此具有类似NO的扩张血管活性。量效关系研究表明，化合物11在高、中、低剂量时均能使得乙酰胆碱的扩血管活性恢复到正常水平，因此值得进行治疗内皮功能障碍的深入研究。
论文同时对分离得到的化合物进行了抗氧化活性的筛选，抗氧化试验结果表明11、14、18、19、20具有较好的抗氧化活性，高、中、低浓度时其活性与阳性对照维生素E相当。
论文中分到四个间苯三酚类苷及其苷元，为此我们对间苯三酚类化合物的结构、生源及生物合成、生物活性和波谱特征进行了综述。
菲骈吲哚里西丁类生物碱是萝摩科娃儿藤属植物中主要生物碱成分，该类化合物被证明具有抗肿瘤活性，本试验室从三分丹和卵叶娃儿藤中分离得到的新天然产物(+)-13a-去氧娃儿藤宁(Deoxytylophorinine CAT-1)经药理筛选具有较强的抗肿瘤活性。本论文对化合物CAT-1进行了手性全合成的探索。利用对甲氧基苯甲醛与3，4-二甲氧基苯乙酸经Perking缩合得到(E)-2-(3，4-二甲氧苯基)-3-(4-甲氧苯基)-2-丙烯酸，该酸甲酯化后经Diels-Alder反应生成菲环结构3，6，7-三甲氧基-9-菲酸甲酯，该酯经还原胺化生成1-[3，6，7-三甲氧基-9-菲甲基]-四氢-2-吡咯酸甲酯，引入手性含氮五元环，再经还原生成β-胺基醇取代的菲环化合物[1-(3，6，7-三甲氧基-9-菲基)-甲基]-四氢-2-吡咯醇，该醇进行分子内傅克烷基化反应，试图得到手性保持的飞骈吲哚里西啶类骨架的产物，未能成功。
同时设计了进行了β-胺基醇取代二苯乙烯进行分子内亲核取代反应，试图得到手性保持的沙普溶型生物碱，再Diels-Alder反应构建菲骈吲哚里西啶类骨架。本路线采用对甲氧基苯甲醛和3，4-二甲氧基苯乙酸缩合得到(E)-2-(3，4-二甲氧苯基)-3-(4-甲氧苯基)-2-丙烯酸，该酸经酰氯与手性氨基酸(L-脯氨酸甲酯)反应，得到1-[(顺)-2-(3，4-二甲氧-苯基)-3-(4-甲氧-苯基)-2-丙烯酰基]-2-吡咯酸甲酯。产物经还原后得到1-[(顺)-2-(3，4-二甲氧-苯基)-3-(4-甲氧-苯基)-2-丙烯酰基]四氢-2-吡咯烷醇，将该醇的氮原子氧化后与甲磺酰氯反应生成相应的甲磺甲磺酸酯。论文试图由该酯在碱性条件下实现关环，得到菲骈吲哚里西啶类骨架，但未能成功。论文同时也用1-[(顺)-2-(3，4-二甲氧-苯基)-3-(4-甲氧-苯基)-2-丙烯酰基]四氢-2-吡咯烷醇进行了傅克反应，试图关环，未能成功。
在试验过程中得到由1-[(顺)-2-(3，4-二甲氧-苯基)-3-(4-甲氧-苯基)-2-丙烯酰基]四氢-2-吡咯烷醇进行甲磺酰化时未能得到相应的甲磺酰酯，而是得到羟基被氯代的产物2-氯甲基1-[(顺)-2-(3，4-二甲氧-苯基)-3-(4-甲氧-苯基)-2-丙烯酰基]四氢-2-吡咯烷，该氯代物在NaH／DMF条件下反应，得到N，N-二甲基-1-[(顺)-2-(3，4-二甲氧-苯基)-3-(4-甲氧-苯基)-2-丙烯酰基]-甲氨
Lysidice rhodostega Hance is a traditional medicine used in China for the treatment of trauma, acesodyne and fractures by local folks for long time. The plant is widely distributed in Guangxi, Guangdong, Yunnan, Guizhou and Taiwan provinces of China. To our knowledge, no phytochemical investigation about this plant has been described in literature up to now.Bioassay-directed separation of the ethanol extract of the roots of the title plant led to the isolation of ten new compounds l-10(compound 10 is artificial) and twenty-four known ones 11-34. On the basis of chemical and spectra analysises, these compounds were elucidated as lysidiside A (1), lysidiside B (2). lysidiside C (3) lysidiside D(4), mopanolchin (5), 7-O-mopanol-β-D-glucopyranoside (6), E-4',5-di-hydroxystilbene-3-O-[α-L-rhamnopyranosyl]-(1→2)-β-D-xylcopyranoside, (7) Z-4',5-dihydroxy-stilbene-3-O-[α-L-rhamnopyranosyl]-(1→2)-β-D-xylcopyranoside (8) 2R, 3R-epicatichin-3-3',5'-dimethoxy-gallate (9)n lysidiside A_2(10), 1-β-methylbutyryl) phloroglucinol (11), polydatin (12), E-resveratrol-3-O-β-D-xylopyranoside (13), resveratrol (14), (-)-5'-methoxyisolariciresinol 3α-O-β-D-glucopyranoside (15), (+)-5'-methoxyisolari-ciresinol-3α-O-β-D-glucopyranoside (16), (-)-lyoniresinol 3α-O-β-D-glucopyranoside (17), (+) mopanol (18), (-)-epicatechin -3-O- gallte (19), cpicatechin (20), naringenin (21), eriodictyol (22), luteolin (23), 3',4',7-trihydroxyflavone (24), (-)-robinetinidol (25), lupeol (26), 2-hydroxyl-lupeol (27), betulinic acid (28), sitosteryl 3β-glucoside 6'-O-palmitate (29), heneicosanic-3-O-β-sitosterolate (30), daucosterol (31),β-sitosterol (32), gallic acid (33) and palmitic acid (34). All of these compounds were isolated from the title plant for the first time.The Endothelium-dependent vasodilation of the isolated compounds were investigated. It was found that compound 1, 2, 3, 6, 11, 12, 13, 18 inhibited phenylepherine -induced vasoconstriction in the rat aortic rings in the presences of Indomethacin (COX inhibitor ) and N~ω-L-nitro-arginine (NOS inhibitor). Compound 11 was proved to be active at low, middle and high concentrations, which mean the compound was worthy of being further investigated for the treatment of endothelium malfunction.
Furthermo re, antioxyside activities of the isolated compounds were also investigated. It was showed that the inhibitor abilities of compounds 11, 14, 18, 19, 20 were almost equivalent as those of the positive control agent vitamin E at high, middile and low concentrations.
Four phloroglucinol glycosides and their aglycone had been isolated from this plant so that we reviewed the structures, bioresouces, biosynthesis, bioactivity and spectral character of this kind of compounds.
Phenanthroindolizidine alkaloids, which were the main alkaloid constituents of Tylophora, were proved to be cytotoxic. The new cytotoxic natural product deoxytylophorinine (CAT-1) was isolated from Tylophora overta by our group for the first time.
In this paper, the primary chiral total synthesis of the CAT-1 has been studied. Compound (E)-2-(3, 4-dimethoxyphenyl)-3-(4-methoxyphenyl)-2-propenoic acid, synthesized from 2-(3, 4-dimethoxyphenyl)-acetic acid and 4-methoxybenzaldehyde by Perking reaction, was methylated and than reducted to the corresponding alcohol. The alcohol was oxidated to afford the corresponding aldehyde. Compound 1-[(3, 6, 7 -trimethxyl-4b, 10-dihydro-9-phenathrenyl-methyl)-2-pyrrolidine carboxylate was later synthesized by N-deprotection-reduction form the above aldehyde and L- proline methl ester. The corresponding pyrrolidine carboxylate was further reducted to 1-[3, 6, 7-trimethoxy-9-phenanthryl]-tetrahydro-2-pyrrolyl]-methanol. Friedel- -Crafts reaction was used in order to obtain the asymmetric deoxytylophorinine form the above methanolic ramification but failed.
Another scheme was designed for deoxytylophorinine form chiral septicine by Diels-Alder reaction. In this scheme, compound methyl-1-[(E)-2-(3, 4-dimethoxyl- -phenyl)-3-(4-methoxylphenyl)-2-propenoyl]-2-pyrrolidine carboxylate, which was obtained from (E)-2-(3, 4-dimethoxyphenyl)-3-(4-methoxyphenyl)-2-pro- -penoic acid and L-proline methl ester, was designed. This carboxylate was than reducted to amino alcohol 1-[(E)-2-(3, 4-dimethoxyl phenyl)-3-(4-methoxylphenyl)- 2-propenoyl]-tetrahydro-2-pyrrolyl methanol. The amino alcohol was oxidated to N-oxide compound and further mesylated by methanesulfonyl chloride to afford the corresponding mesylate. We want to get chiral septicine alkaloid under base conditions from this mesylate but failed. The septicine alkaloid could not be synthesized using Friedel-crafts reaction from the amino alcohol or its N-oxide compound ether.
An unexpected compound 2-chloromethyl-1-[(E)-2-(3, 4-dimethoxylphenyl)-3- (4-methoxyl-phenyl)-2-propenoyl]-pyrrolidine was obtained during the mesylated by methanesulfonyl chloride from the 1-[(E)-2-(3, 4-dimethoxyl phenyl)-3-(4-methoxyl- -phenyl)-2-propenoyl]-tetrahydro-2-pyrrolyl methanol under standard mesylated conditions. To our surprise, this halide was tansported to N, N-dimethyl-1-[(E)-2-(3, 4- dimethoxyl-phenyl)-3-(4-methoxylphenyl)-2-propenoyl]-tetrahydro-2-pyrrolylmethane -mine in the presences of sodium hydride and anhydrous DMF.
引文
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