Stereochemistry of microbial transformation of (+)- and (-)-2'-demethoxydehydrogriseofulvin by Streptomyces cinereocrocatus.

Abstract

To elucidate the stereochemistry of microbial hydrogenation of (+)- and (-)-2'-demethoxydehydrogriseofulvin (1 and 2) by Streptomyces cinereocrocatus NRRL 3443, deuterated substrates (1a, 1b, 2a, and 2b) were synthesized from (+) -griseofulvin (9) and subjected to microbial transformation. The 41.41 MHz 2H nuclear magnetic resonance (NMR) and 400 MHz 1H NMR studies clearly revealed that the microbial hydrogenations of (+)- and (-)-2'-demethoxydehydrogriseofulvin (1 and 2) proceed stereospecifically with an anti-addition of hydrogens at the 2' and 3' positions. Further, the microbial transformation of 1 to (+) -2'-demethoxy-2', 3'-dihydrodehydrogriseofulvin (5) indicates an isomerization by the microorganism of 1 to the enantiomer, (-)-2'-demethoxydehydrogriseofulvin (2), which is further hydrogenated to afford 5.