Microbial Transformation of (+)- and (−)-Dehydrogriseofulvin by Streptomyces Species Analyzed by ²H Nuclear Magnetic Resonance Spectroscopy

To elucidate the stereochemical course of the microbial transformation of (+)-dehydrogriseofulvin (DGF) by Streptomyces species, (+)-[5′-²H]DGF, which was obtained by dehydrogenation of (+)-[5′ α,5′ β-²H]epigriseofulvin, was incubated with S. cinereocrocatus. The structure of the product was identified as (+)-[5′ α-²H]griseofulvin (GF) by ²H nuclear magnetic resonance spectroscopy. The results of incubations of (−)- and (+)-DGF with eight Streptomyces species (S. cinereocrocatus, S. roseochromogenus, S. bikiniensis, S. griseinus, S. durhamensis, S. californicus, S. fimbriatus, and S. cinereoruber) showed that (−)- and (+)-DGF were isomerized to each other and converted to (+)-GF as the main product, although some (−)-GF was also formed depending on the microorganisms used. In particular, incubation of (+)-DGF with S. cinereoruber yielded (−)-GF as the main product. In addition, (±)-DGF was transformed by S. cinereocrocatus to the naturally occurring (+)-GF in 48% yield. The enantiomer ratios of DGF and GF obtained by microbial transformation were calculated from the [α]_D values of corresponding enantiomer mixtures.