Ro 22-5417, a new clavam antibiotic from Streptomyces clavuligerus. III. Absolute stereochemistry.

Abstract

The complete stereostructure of the new antibiotic Ro 22-5417 has been established as 3-[(3S,5S)-7-oxo-1-aza-4-oxabicyclo[3.2.O]hept-3-yl]-L-alanine. This result together with the synthesis of an (3R,5R)-L-analog allowed us to postulate that clavams require the R-configuration at the ring juncture for beta-lactamase inhibitory activity, while the opposite S-stereochemistry is essential for antifungal activity.