C_(19)-二萜生物碱官能化A/E双环的不对称合成  

Asymmetric synthesis of the functionalized A/E bicyclic fragment of the C_(19)-diterpenoid alkaloids

作　　者：陈家骏 侯文龙 季久健 刘小宇[1] 秦勇[1] Jiajun Chen;Wenlong Hou;Jiujian Ji;Xiao-Yu Liu;Yong Qin(Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province,Sichuan Engineering Laboratory for Plant-Sourced Drug,Sichuan Research Center for Drug Precision Industrial Technology,West China School of Pharmacy,Sichuan University,Chengdu 610041,China)

机构地区：[1]四川大学华西药学院,靶向药物与释药系统教育部重点实验室,四川省植物来源药物工程实验室,四川省小分子药物精准化工程技术研究中心,成都610041

出　　处：《中国科学：化学》2023年第3期550-557,共8页SCIENTIA SINICA Chimica

基　　金：国家自然科学基金(编号:22071161,21871189)资助项目。

摘　　要：C_(19)-二萜生物碱是一类具有重要生物活性的天然产物,在结构上以复杂的笼状骨架和稠密的取代基团为特点.相似的A/E氮杂桥环体系普遍存在于C_(19)-二萜生物碱中,其高效制备是合成相应天然产物的重要基础.本研究从非手性前体出发,通过去对称化、立体选择性烯丙基化、Aldol羟甲基化及还原胺化反应等关键步骤,完成了C_(19)-二萜生物碱官能化A/E双环的不对称合成.The C_(19)-diterpenoid alkaloids belong to a class of natural products with significant biological activities.These molecules are structurally characterized by complex cage-like skeletons and dense functional substituents.The efficient preparation of the A/E aza-bridged ring system,which is ubiquitous in C_(19)-diterpenoid alkaloids,would lay an important foundation for their total synthesis.This paper reports a new asymmetric synthesis of the functionalized A/E bicyclic fragment of the C_(19)-diterpenoid alkaloids,featuring desymmetrization,diastereoselective allylaltion,aldol hydroxymethylation,and reductive amination as key steps.

关 键 词：二萜生物碱 全合成 不对称合成 A/E双环 

分 类 号：O629.3[理学—有机化学]