Ck. Lee et al., STEREOSPECIFIC REDUCTION OF VIRGINIAMYCIN M(1) AS THE VIRGINIAMYCIN RESISTANCE PATHWAY IN STREPTOMYCES-VIRGINIAE, Antimicrobial agents and chemotherapy, 40(3), 1996, pp. 595-601
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.