天然产物haouamine a的合成方法研究-study on the synthesis method of natural product hawuamine a.docx

 天然产物 Haouamine A 的合成方法研究 中 文 摘 要 目的：本文采用廉价易得的商业试剂通过简单的操作方法和普通的 实验条件，运用高效的合成策略人工合成 Haouamine A，并将这一合成策 略用以 Haouamine A 工业生产，从而缓解 Haouamine A 科研市场供不应 求的现状。 OH OH OH OH N H 图 1 Haouamine A 生物碱的结构 方法：（1）以间羟基苯乙酸为起始原料应用 Suzuki 交叉偶联反应等 几步反应合成联苯化合物。（2）以 3-氯丙酸为原料经历傅-克重排反应、 甲基化、Sharpless 不对称双羟化、氧化、还原胺化、分子内扩环重排反 应等 11 步反应合成茚并四氢吡啶环。（3）以 1,3-丙酮二羧酸二甲酯为原 料经缩合、甲基化、Birch 还原等 6 步反应合成环己烯酮化合物，再将 茚并四氢吡啶环与环己烯酮化合物连接起来合成化合物 52。 结果：合成了 42 个化合物，其中采用创新方法合成了 33 个化合物； 通过 11 步反应，??产率 8%（直线合成 7 步，总收率 16%）首次合成联 苯化合物；通过简单的 5 步反应以 18%总收率创造性的合成环己烯酮化 合物。最终获得由茚并四氢吡啶环与环己烯酮化合物连接起来的中间体 化合物 52。 结论：采用操作简单的方法高效合成了联苯化合物与环己烯酮化合 物这两个中间体，为有机合成及应用尤其是为联苯类化合物和环己烯酮  类化合物的合成研究具有实用的参考价值。同时为有机全合成 Haouamine A 合成研究提供了参考，并为推动有机合成的发展尤其是对新药研发打 下了坚实的合成基础。 关键词： Haouamine A，四氢吡啶环，对环芳烷，全合成，抗癌  Synthetic studies of Haouamine A ABSTRACT Objective: In this paper, an efficient synthetic strategy was complied to complete Haouamine A synthesis. This strategy was starting from commercial material and using simple operation procedure and common experimental conditions. It also can be adapted for Haouamine A industrial production to alleviate the present situation which was in short supply in market. Methods: (1)Starting from 3-Hydroxyphenylacetic acid and using Suzuki cross-coupling reaction, biphenyl compounds were synthesized. (2)Starting from 3-chloropropionic acid, indeno tetrahydropyridine was synthsized through 11 steps which includes Friedel -Crafts rearrangement methylation, Sharpless asymmetric dihydroxylation, oxidation, reduct amination, intramolecular ring expanding rearrangement etc. reactions. (3)Starting from dimethyl 1,3-acetonedicarboxylate, it took 6 steps which includes condensation, methylation, Birch reduction etc. to synthesize cyclohexene ketone compounds. Then the indeno tetrahydropyridine was coupled with cyclohexene ketone compound to synthesize 52. Results: Total 42 compounds were successfully synthesized in which 33 compounds were through innovative approach. Biphenyl compounds were synthesized for the