STEREOSPECIFIC REDUCTION OF VIRGINIAMYCIN M(1) AS THE VIRGINIAMYCIN RESISTANCE PATHWAY IN STREPTOMYCES-VIRGINIAE

In a cell extract of Streptomyces virginiae, virginiamycin M(1) was in activated in the presence of NADPH, while virginiamycin S remained int act, The inactivated product of virginiamycin M, was isolated, and str ucture analysis revealed that the inactivation involves reduction of a C-16 carbonyl group leading to the formation of 16-dihydrovirginiamyc in M(1). Acetonide and benzylidene acetal derivatives were synthesized from the two hydroxyl groups on C-14 and C-16, and the C-16 stereoche mistry was determined by C-13 nuclear magnetic resonance spectroscopy, Two methyl groups of the acetonide derivative gave C-13 signals of 20 .1 and 30.1 ppm, indicating that the relative stereochemistry of the C -14 and C-16 hydroxy groups is syn, Furthermore, irradiation of the be nzylidene methine proton gave clear nuclear Overhauser effect enhancem ent of the C-14 or C-16 methine protons, indicating that H-14 and H-16 were in an axial configuration, From the (14S) absolute configuration of natural virginiamycin M(1) and the syn relative configuration for the C-14 and C-16 hydroxyl groups of the inactivated product, the C-16 absolute configuration of the inactivated product was thus identified as R.