Enantioselective Route to Platensimycin: An Intramolecular Robinson Annulation Approach

Abstract

An enantioselective route to the tetracyclic core structure of the novel antibiotic lead compound platensimycin is accomplished in 10 steps from simple commercially available starting materials. Highlights of this synthesis include (1) a regio- and enantioselective Diels−Alder reaction between methyl acrylate and methyl cyclopentadiene to give adduct 2 with essentially complete regio-, diastereo-, and enantiocontrol; (2) oxidative decarboxylation of ester 2 using nitrosobenzene; (3) a one-pot reductive cyanation of lactone 4; (4) a stereoselective intramolecular Michael addition between an α-branched aldehyde moiety and a β-substituted enone part of 8, followed by aldol dehydration in one pot to give the Robinson annulation product 9.