title: Collective synthesis of Lycopodium alkaloids and tautomer locking strategy for the total synthesis of (-)-lycojapodine A.
abstract: The collective total synthesis of Lycopodium alkaloids (+)-fawcettimine (1), (+)-fawcettidine (2), (+)-alopecuridine (4), (-)-lycojapodine A (6), and (-)-8-deoxyserratinine (7) has been accomplished from a common precursor (15) based on a highly concise route inspired by the proposed biosynthesis of the fawcettimine- and serratinine-type alkaloids. An intramolecular C-alkylation enabled efficient installation of the challenging spiro quaternary carbon center and the aza-cyclononane ring. The preparation of the tricyclic skeleton as well as the establishment of the correct relative stereochemistry of the oxa-quaternary center were achieved by hydroxyl-directed SmI(2)-mediated pinacol couplings. An unprecedented tandem transannular N-alkylation and removal of a Boc group was discovered to realize a biosynthesis-inspired process to furnish the desired tetracyclic skeleton. Of particular note is the unique and crucial tautomer locking strategy employed to complete the enantioselective total synthesis of (-)-lycojapodine A (6). The central step in this synthesis is the late-stage hypervalent iodine oxidant (IBX or Dess-Martin periodinane)/TFA-mediated tandem process, which constructed the previously unknown carbinolamine lactone motif and enabled a biomimetic transformation to generate (-)-lycojapodine A (6) in a single operation.
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Houhua
authors.initials: H
authors.lastname: Li
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wang
authors.forename: Benke
authors.initials: B
authors.lastname: Hong
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Lei
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D001372:Aza Compounds / Q000737:chemistry; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry; D007783:Lactones / Q000737:chemistry; D032502:Lycopodium / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D001372:Aza Compounds; D006576:Heterocyclic Compounds, 4 or More Rings; D007783:Lactones; C559183:alopecuridine; C524731:fawcettimine; C539671:lycojapodine A