Facile entry to substituted decahydroquinoline alkaloids. Total synthesis of lepadins A-E and H
Facile entry to substituted decahydroquinoline alkaloids. Total synthesis of lepadins A-E and H
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DOI：
10.1021/jo061070c
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发表时间：
2006-08-18
影响因子：
3.6
通讯作者：
Ma, Dawei
中科院分区：
文献类型：
--
作者：
Pu, Xiaotao;Ma, Dawei
L-丙氨酸衍生的δ-溴-β-甲硅烷基氧基-丙胺与1，3-环己二酮缩合，然后烷基化环化产生双环烯酮。该烯酮在HOAc中的非对映选择性Pt/C催化氢化提供5-氧代-顺式-稠合十氢喹啉。该十氢喹啉的Wittig烯化和随后所得5-甲酰基中间体的差向异构化仅产生5-β-甲酰基十氢喹啉。在平行程序中，该十氢喹啉的彼得森反应和随后所产生的5-外-烯烃的氢化提供了主要具有5-α-取代基的十氢喹啉。对于这两个非对映选择性方法，使用没有N-保护的中间体作为底物是必要的，因为相应的N-Boc中间体给出差的非对映选择性。具有β-型侧链的中间体通过碳链延长进一步转化为lepadins A-C，而具有α-型侧链的中间体通过与由两个Sharpless环氧化产物产生的两个砜连接而转化为lepadins D、E和H以及相应的5 ′-差向异构体。通过旋光度和核磁共振数据的比较，将lepadins D、E和H的立体化学结构归属为2S，3R，4aS，5S，8aR，5 'R。
Condensation of a L-alanine derived delta-bromo-beta-silyloxy-propylamine with 1,3-cyclohexadione followed by alkylative cyclization produces a bicyclic enone. Diastereoselective Pt/C-catalyzed hydrogenation of this enone in HOAc provides a 5-oxo-cis-fused decahydroquinoline. Wittig olefination of this decahydroquinoline and subsequent epimerization of the resulting 5-formyl intermediate gives rise to a 5-beta-formyl decahydroquinoline exclusively. In a parallel procedure, Peterson reaction of this decahydroquinoline and subsequent hydrogenation of the generated 5-exo-olefin provides a decahydroquinoline with a 5-alpha-substituent predominantly. For these two diastereoselective processes, using the intermediates without N-protection as the substrates is essential because the corresponding N-Boc intermediates give poor diastereoselectivity. The intermediate with beta-form side chain is further converted into lepadins A-C via carbon chain elongation, while the intermediate with alpha-form side chain is transformed into lepadins D, E, and H and corresponding 5'-epimers via connection with two sulfones generated from two Sharpless epoxidation products. By comparison of the rotations and NMR data, the stereochemistry of lepadins D, E, and H is assigned as 2S, 3R, 4aS, 5S, 8aR, 5'R.