Microbial transformations of natural antitumour agents. Part 15. Metabolism of bruceantin by Streptomyces griseus

Abstract

Microbial transformations were conducted with the quassinoid bruceantin (1). Screening studies with 193 micro-organisms provided several streptomycetes capable of accumulating bruceantin metabolites. Streptomyces griseus(ATCC 10137) totally metabolized bruceantin within 19 h, and a preparative-scale incubation using bruceantin provided bruceine C (4), bruceantin 4′,5′-epoxide (3), and bruceantin-5′-ol (5). Structures of metabolites were assigned based on their ¹H n.m.r. and mass spectral characteristics. Metabolites (3) and (5) are novel analogues of bruceantin, and are formed by an unusual pathway involving oxidation of bruceantin, probably through the unisolated 4′,5′-bruceantin olefin (2) to the epoxide (3), which serves as an obligatory precursor for bruceine C (4) and bruceantin-5′-ol (5).