Divergent and Efficient Syntheses of the Lycopodium Alkaloids (-)-Lycojaponicumin C, (-)-8-Deoxyserratinine, (+)-Fawcettimine, and (+)-Fawcettidine
Divergent and Efficient Syntheses of the Lycopodium Alkaloids (-)-Lycojaponicumin C, (-)-8-Deoxyserratinine, (+)-Fawcettimine, and (+)-Fawcettidine
复制标题
石松生物碱 (α)-LycojaponicuminαC、(α)-8-脱氧舍拉汀、( )-Fawcettimine 和 ( )-Fawcettidine 的多样化高效合成
DOI：
10.1002/anie.201306369
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发表时间：
2013-10-18
影响因子：
16.6
通讯作者：
Zhang, Xiao-Ming
中科院分区：
文献类型：
--
作者：
Hou, Si-Hua;Tu, Yong-Qiang;Zhang, Xiao-Ming
The fawcettimine class of Lycopodium alkaloids are a class of structurally unique natural molecules with more than 80 members,[1] among which lycojaponicumin C (1),[2] 8-deoxyserratinine (2),[3] fawcettimine (3),[4] and fawcettidine (4)[5] are representative ones (Figure1). In particular, the alkaloid 1 isolated by Yu and co-workers from the traditional Chinese medicine (L. japonicum THUNB) possesses biological activity.[2] The structures of the alkaloids of the fawcettimine class feature the fused tetracyclic ABCD frameworks including two common AB rings and two differently-sized CD rings together with highly crowded quaternary stereocenters. Because of their wide-ranging biological activities and challenging structures, syntheses of these alkaloids have attracted great attention, and several total syntheses have been accomplished.[6, 7] Many of these strategies make use of the key 6/5/9 tricyclic intermediate 7 (Scheme 1), which is prepared at least in 10 steps from readily available material.[6f, i] Using a similar intermediate, we also have finished the total synthesis of sieboldine A.[7f] Our next attempt toward this subject is to explore a more efficient divergent strategy through designing a versatile common intermediate such as 8, which contains a 6/5/5 polycyclic system rather than the 6/5/9 system in 7 but contains an azido chain. We expect such an advanced intermediate allows access not only to the alkaloids 2–4 via subintermediate 6, but also to other important molecules. Here, we report the first asymmetric total synthesis of 1 and the improved total syntheses of 2–4 by using this proposal.
