天然产物Arborisidine四环骨架的不对称合成
收稿日期: 2018-05-10
修回日期: 2018-06-04
网络出版日期: 2018-06-15
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
Received date: 2018-05-10
Revised date: 2018-06-04
Online published: 2018-06-15
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
陈志涛 , 肖涛 , 宋颢 , 秦勇 . 天然产物Arborisidine四环骨架的不对称合成[J]. 有机化学, 2018 , 38(9) : 2427 -2434 . DOI: 10.6023/cjoc201805025
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.
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