Asymmetric Synthesis of a Structurally Simplified Analogue of the Antibiotic Heptelidic Acid

Summary.

 A structurally simplified analogue of the antibiotic (+)-heptelidic acid was synthesized in ten steps with an overall yield of 9%. Key step was a conjugate addition of a silyl protected vinylcuprate to an asymmetrically shielded enoate, which gave an adduct as a single diastereomer. Transesterification in the presence of triethylamine allowed a selective cleavage of the chiral auxiliary and afforded an enantiomerically pure methyl ester. This easily enolizable β-ketoester was transformed to the trans configurated methylene derivative using a four-step reaction sequence. Finally, the desired epoxylactone was accessible from the methylene derivative by lactone ring formation and successive oxidation in four steps.