title: The discovery of a novel route to highly substituted α-tropolones enables expedient entry to the core of the gukulenins.
abstract: A simple and general method for the synthesis of highly substituted α-tropolone ethers that allows rapid access to the bis(tropolone) core of the antiproliferative metabolites (-)-gukulenins A and F (3, 4) is described. The reaction proceeds by thermolytic opening of gem-dibromobicyclo[4.1.0]heptane intermediates, which are readily accessed from simple starting materials. Mechanistic studies suggest the reaction proceeds via an autocatalytic process mediated by methyl hypobromite. This synthetic sequence allows access to a broad array of highly substituted α-tropolones.
authors.affiliation: Department of Chemistry, Yale University, New Haven, Connecticut 06520, United States.
authors.forename: Roman
authors.initials: R
authors.lastname: Kats-Kagan
authors.affiliation: Department of Chemistry, Yale University, New Haven, Connecticut 06520, United States.
authors.forename: Seth B
authors.initials: SB
authors.lastname: Herzon
mesh_terms: D004987:Ethers / Q000138:chemical synthesis / Q000737:chemistry; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism; D013729:Terpenes / Q000138:chemical synthesis* / Q000737:chemistry; D014334:Tropolone / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D004987:Ethers; D006576:Heterocyclic Compounds, 4 or More Rings; D013729:Terpenes; C549725:gukulenin A; D014334:Tropolone