Biosynthetic investigations of the v-type ATPase inhibitors bafilomycin A(1), B-1 and concanamycin A

Abstract

The plecomacrolides bafilornycin A(1) and B-1 (1, 2) and concanamycin A (3), produced by different Streptomyces species, show a unique macrolactone structure with characteristic side chains and exhibit striking biological activities including distinct V-type ATPase inhibition. The biosynthesis of 1 and 2 has been established by feeding experiments with C-13-labelled precursors. Both, bafilomycin (1, 2) and concanamycin. (3) feature an "unusual C-2 chain extension unit" of as yet unknown origin which was addressed by feeding labelled 2-hydroxy- and 2-methoxymalonyl-derivatives.