天然产物Arborisidine四环骨架的不对称合成  

Asymmetric Synthesis of the Tetracyclic Skeleton of Natural Product Arborisidine

作　　者：陈志涛[1] 肖涛[1] 宋颢[2] 秦勇[2] Chen Zhitao1,Xiao Tao1,Song Hao2,Qin Yong2(a School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331;b West China School of Pharmacy, Sichuan University, Chengdu 61004)

机构地区：[1]重庆大学药学院,重庆401331 [2]四川大学华西药学院,成都610041

出　　处：《有机化学》2018年第9期2427-2434,共8页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(Nos.21572140;21732005)资助项目~~

摘　　要：报道了吲哚生物碱arborisidine四环骨架的不对称合成研究.以本课题组前期报道的光学纯化合物10,9-二叔丁基-5-乙基(4S,8R)-7,8-二羟基-9H-8a,4b-(氨基乙醇氨基)-咔唑-5,9,10-三羧酸酯(11)为起始原料,经Krapcho反应脱羧转化为酮后,通过还原开环策略实现酮中间体四氢吡咯环的开环;随后经两次Saegusa氧化反应和Michael加成反应,实现了A/B/D三环中间C(15)-C(16)双键的构建和C(16)位甲基取代的引入.最后经分子内氮杂Michael加成反应一步实现arborisidine中哌啶C环和C(16)季碳中心的建立,高效完成目标分子A/B/C/D四环骨架的不对称合成.Asymmetric synthesis of the tetracyclic skeleton of arborisidine is reported. Starting from the enantiomerically pure compound 10,9-di-tert-butyl5-ethyl（4 S,8 R）-6-hydroxy-7,8-dihydro-9 H-8 a,4 b-（epiminoethano）carbazole-5,9,10-tricarboxylate（11） which was reported earlier by our group, a Krapcho decarboxylation reaction was used to afford the ketone, and then a reductive ring-opening method was applied to open the pyrrolidine ring of the substrate. The C（15）-C（16） double bond and the methyl group at C（16） of A/B/D tricyclic skeleton were introduced via Saegusa oxidation and Michael reaction, respectively. Finally, an intramolecular aza-Michael addition reaction was used as a key reaction to construct the C-ring and C（16） quaternary center, which led to the efficiently asymmetric synthesis of A/B/C/D tetracyclic skeleton of arborisidine.

关 键 词：吲哚生物碱 arborisidine Saegusa氧化 氮杂Michael加成 不对称合成 

分 类 号：O629.3[理学—有机化学]