title: Total synthesis of manzamine A and related alkaloids.
abstract: Total syntheses of three structurally complex marine natural products, manzamine A, ircinol A, and ircinal A, are reported. The route pivoted on the construction of a late-stage protecting-group-free pentacyclic enol triflate coupling partner, from which all three family members were accessed divergently via palladium-catalyzed reactions. The rapid synthesis of this key pentacyclic enol triflate was achieved by a highly convergent union of five fragments through a stereoselective Michael addition, a three-component nitro-Mannich lactamization cascade, an unprecedented and highly stereoselective reductive nitro-Mannich cyclization cascade, a stereoselective organometallic addition, and a Z-selective alkene ring-closing metathesis. Altogether this chemistry has allowed the shortest synthetic route to date for manzamine A (18-step longest linear sequence) via a late-stage diversification point that is ideal for future manzamine A analogue synthesis.
authors.affiliation: Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK.
authors.forename: Pavol
authors.initials: P
authors.lastname: Jakubec
authors.forename: Alison
authors.initials: A
authors.lastname: Hawkins
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Felzmann
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Dixon
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D002227:Carbazoles; C078290:manzamine A