单萜吲哚生物碱钩吻素子的全合成研究

Gelsemium alkaloids attract remarkable attention due to their diverse and intricate molecular structures as well as significant biological activities. Koumine is a skeletal unique member in this class of natural products; only one total synthesis has been accomplished to date. The applicant proposed a concise route toward the total synthesis of koumine, employing a transition metal catalyzed eneyne cycloisomerization for the construction of the highly functionalized piperidine motif, a iridium catalyzed allylic substitution to forge the tetracyclic scaffold, and an indole dearomatizing cyclization for the assembly of the spirocyclic system. This work would found a basis for further synthetic studies of related Gelsemium alkaloids of great biological interest.

钩吻类生物碱因复杂多变的分子结构和显著的生物活性而受到人们的关注。钩吻素子koumine是一个环系独特的单萜吲哚生物碱，到目前为止只有一例全合成报道。申请人计划利用过渡金属催化的烯炔环化异构化反应来合成多取代的哌啶环，利用铱催化的环化反应构建钩吻素子koumine的四环核心，使用吲哚N1位和C3位选择性亲核进攻反应来构建螺环季碳中心，并将它们作为关键步骤来实现钩吻素子koumine的全合成。并为后续的其他活性钩吻生物碱的合成研究打下基础。

《单萜吲哚生物碱钩吻素子的全合成研究》对具有生理和临床价值的一类单贴生物碱koumine展开合成研究。本项目主要：1)发展了吲哚烯炔体系的六员环化方法；2)吲哚选择性烯丙基化反应的探索。同时，还针对吲哚4-位苄位的活性，与中科院合作完成了天然产物epoxyeujindole A的全合成工作。上述成果，为今后相关钩吻家族生物碱的合成开辟了一条新颖的道路。