有机化学 ›› 2018, Vol. 38 ›› Issue (9): 2427-2434.DOI: 10.6023/cjoc201805025 上一篇    下一篇

所属专题: 合成科学

研究论文

天然产物Arborisidine四环骨架的不对称合成

陈志涛a, 肖涛a, 宋颢b, 秦勇b   

  1. a 重庆大学药学院 重庆 401331;
    b 四川大学华西药学院 成都 610041
  • 收稿日期:2018-05-10 修回日期:2018-06-04 出版日期:2018-09-25 发布日期:2018-06-15
  • 通讯作者: 宋颢, 秦勇 E-mail:songhao@scu.edu.cn;yongqin@scu.edu.cn
  • 基金资助:

    国家自然科学基金(Nos.21572140,21732005)资助项目.

Asymmetric Synthesis of the Tetracyclic Skeleton of Natural Product Arborisidine

Chen Zhitaoa, Xiao Taoa, Song Haob, Qin Yongb   

  1. a School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331;
    b West China School of Pharmacy, Sichuan University, Chengdu 610041
  • Received:2018-05-10 Revised:2018-06-04 Online:2018-09-25 Published:2018-06-15
  • Contact: 10.6023/cjoc201805025 E-mail:songhao@scu.edu.cn;yongqin@scu.edu.cn
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos. 21572140, 21732005).

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.

关键词: 吲哚生物碱, arborisidine, Saegusa氧化, 氮杂Michael加成, 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(4S,8R)-6-hydroxy-7,8-dihydro-9H-8a,4b-(epiminoethano)carbazole-5,9,10-tricar-boxylate (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.

Key words: indole alkaloid, arborisidine, Saegusa oxidation, aaz-Michael addition, asymmetric synthesis