State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, China.
J Org Chem. 2011 May 20;76(10):3684-90. doi: 10.1021/jo1023188. Epub 2011 Apr 7.
A unified strategy for total synthesis of the Lycopodium alkaloids (-)-8-deoxyserratinine (7), (+)-fawcettimine (1), and (+)-lycoflexine (4) is detailed. The key features include a highly efficient Helquist annulation to assemble the cis-fused 6/5 bicycle, facile construction of the aza nine-membered ring system employing double N-alkylation strategy, providing access to the common tricyclic skeleton, asymmetric Shi epoxidation, delivering the desired β-epoxide stereospecifically to furnish (-)-8-deoxyserratinine (7), SmI(2) reduction of dihydroxylation derivative 35 to enable formation of (+)-fawcettimine (1), and a rapid biomimetic transformation of (+)-fawcettimine (1) into (+)-lycoflexine (4) via an intramolecular Mannich cyclization.
详细描述了将石松生物碱（-）-8-去氧蛇根精（7）、（+）-法考明（1）和（+）-石松宁（4）全合成的统一策略。关键特点包括高效的Helquist 稠环反应来组装顺式稠合的 6/5 双环，通过双 N-烷基化策略轻松构建氮杂九元环系统，提供常见的三环骨架，不对称 Shi 环氧化，特异性地提供所需的 β-环氧化物，得到（-）-8-去氧蛇根精（7），SmI（2）还原二羟基化衍生物 35 以形成（+）-法考明（1），以及通过分子内 Mannich 环化，快速仿生转化（+）-法考明（1）为（+）-石松宁（4）。
