Terpenoids produced by actinomycetes: isolation, structural elucidation and biosynthesis of new diterpenes, gifhornenolones A and B from Verrucosispora gifhornensis YM28-088

Abstract

New terpenoids named gifhornenolones A (1) and B (2) were isolated from the culture broth of Verrucosispora gifhornensis YM28-088, and their structures were established as hydroxylated isopimaradiene derivatives on the basis of extensive NMR and MS spectral analyses. In addition, a known sesquiterpene compound cyperusol C (3) was isolated. The absolute configuration of 1 was determined by nuclear Overhauser effect spectroscopy (NOESY) and CD spectra as 4R, 5S, 9R, 10S, 13R, and that of 2 was determined by NOESY experiments as 3R, 4R, 5R, 9R, 10S, 13R. Labeling experiments with [1-(13)C]glucose and [U-(13)C(6)]glucose confirmed that the MEP (2-C-methyl-D-erythritol-4-phosphate) pathway was used for the biosynthesis of terpenoids in this organism. 1 showed potent inhibitory activity to the androgen receptor with an IC(50) of 2.8 microg ml(-1).