The squalestatins, novel inhibitors of squalene synthase produced by a species of Phoma. II. Structure elucidation.

Abstract

Three novel fungal metabolites 1-3 isolated from cultures of a Phoma sp. C2932, are potent and selective inhibitors of squalene synthase. Their structures have been determined by a combination of spectroscopic, X-ray crystallographic and chemical methods; these natural products incorporate the highly functionalised bicyclic core, [1S-(1 alpha, 3 alpha, 4 beta, 5 alpha, 6 alpha, 7 beta]-4,6,7-trihydroxy- 2,8-dioxabicyclo-[3.2.1]octane-3,4,5-tricarboxylic acid.