Discovery, Isolation, and Structure Elucidation of a Family of Structurally Unique, Fermentation-Derived Tetracyclic Macrolides

Abstract

Screening of fermentation broths for mosquito larvicidal activity yielded an active culture denoted as A83543. Nine active, structurally-related factors were isolated and purified by extractive and chromatographic procedures. Their structures were elucidated by a combination of spectroscopic (NMR, MS, UV, IR) and X-ray crystallographic methods. Each factor possessed the core structure of a 5,6,5-cis-anti-trans-tricyclic ring system fused to a 12-membered lactone. In addition, an aminosugar (forosamine) and a neutral sugar (2,3,4-tri-O-methylrhamnose) were glycosidically linked to the tetracyclic framework. Absolute stereochemistry was established by comparing samples of forosamine obtained from acidic hydrolyses of A83543A and spiramycin. The novel tetracyclic structure of A83543 suggests that unique features are involved in its biosynthesis. The purified factors exhibited potent mosquito larvicidal activity, but lacked antibiotic activity.