title: Synthesis of alkaloid (-)-205B via stereoselective reductive cross-coupling and intramolecular [3+2] cycloaddition.
abstract: An asymmetric synthesis of alkaloid (-)-205B, a tricyclic member of the architecturally diverse family of natural products isolated from the skin of neotropical poison frogs, is described that proceeds through two recently developed stereoselective synthetic methods: (1) Ti-mediated allylic alcohol-imine reductive cross-coupling and (2) intramolecular [3+2] cycloaddition of a glyoxylate-based homoallylic nitrone. The utility of this latter cycloaddition process for the assembly of the stereochemically dense piperidine core of 205B is noteworthy, as this method enables direct [3+2] cycloaddition of an intermediate homoallylic (E)-nitrone via a pathway that is stereochemically unscathed by competitive [3,3]-sigmatropic rearrangement processes. Overall, the synthesis is asymmetric, concise, and highly stereoselective-features which point to the potential future utility of these chemical methods in natural product synthesis and medicinal chemistry.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458, USA.
authors.forename: Dexi
authors.initials: D
authors.lastname: Yang
authors.forename: Glenn C
authors.initials: GC
authors.lastname: Micalizio
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids