软坚散结中药海藻有效成分卡英酸合成方法研究进展

Kainic Acid Synthesis Research of Traditional Chinese Medicine Seaweed Active Ingredients

简述了肿瘤药物海藻中有效成分卡英酸结构确定,其结构为2-羧酸-3-羧甲基-4-异丙烯基吡咯烷;综述了卡英酸尤其是(-)-?-Kainic acid全合成及其方法学研究;详细说明了卡英酸吡咯烷环骨架及相连的三取代手性中心的构建途径,构建途径分为单一碳碳键的连接和多个碳碳键的连接及其他途径,其中单一碳碳键途径包括aldol reaction策略、以Zn为载体的钯催化ene-cyclizations策略和铹催化ene-cycloisomerization策略,多个碳碳键途径包括对甲烯基环丙烷扩环策略、[3+2]环化策略和串联michael addition-cyclization策略;最后展望了卡英酸全合成的今后发展。

The Kainic acid structure was introduced briefly which was 2-carboxylic acid-3-carboxy methyl-4-isopropenyl pyrrolidine. It was summarized the ways of synthesis and methodology of Kainic acid, especially （-）-alpha Kainic acid. This artical detailed the constructio approach to the Kainic acid pyrrolidine ring skeleton and substituted chiral centre, and those synthetic ways could be divided into ＂single bond connections＂ and ＂multiple bond connections＂. On one hand, ＂single bond connections＂ included enantioselective aldol reaction strategy, Zn-Mediated ene cyclizations strategy and diastereoselective Rhodium-catalyzed ene-cycloisomerization reactions and so on. On the other hand, synthetic strategy of ＂multiple bond connections＂ contained diastereoselective methyleecyclopropane ringexpansion, diastereoselective intrarnolecular [3＋2] cycloaddition reaction and Cu-catalyzed Michael addition-cyclization reaction strategy. Finally the prospect of synthetic ways of he Kainic acid in the future was discussed.