title: Application of the Helquist annulation in Lycopodium alkaloid synthesis: unified total syntheses of (-)-8-deoxyserratinine, (+)-fawcettimine, and (+)-lycoflexine.
abstract: 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.
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, China. yangyurong@mail.kib.ac.cn
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Yang
authors.forename: Liang
authors.initials: L
authors.lastname: Shen
authors.forename: Jiu-Zhong
authors.initials: JZ
authors.lastname: Huang
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.forename: Kun
authors.initials: K
authors.lastname: Wei
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000737:chemistry; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000737:chemistry; D007212:Indolizines / Q000138:chemical synthesis / Q000737:chemistry; D032502:Lycopodium / Q000737:chemistry*
chemical_list: C553068:8-deoxyserratinine; D000470:Alkaloids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006576:Heterocyclic Compounds, 4 or More Rings; D007212:Indolizines; C559183:alopecuridine; C524731:fawcettimine; C555161:lycoflexine