27 MICROBIAL TRANSFORMATION OF (-)- AND (+)-DEHYDROGRISEOFULVIN BY STREPTOMYCES SPECIES
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The microbial transformation of (-)-dehydrogriseofulvin (1a) to (+)-griseofulvin (2a) was initially investigated by Andres et al. using Streptomyces cinereocrocatus NRRL 3443. Since then, by means of ^2H NMR we showed the stereo-chemical course of the microbial hydrogenation of natural (-)-[5'-^2H]dehydrogriseofulvin (1b) into natural (+)-[5'α-^2H]griseofulvin (2b) by the same microorganism. We now proved that in the microbial transformation by S. cinereocrocatus (+)-[5'-^2H]dehydrogriseofulvin (3b) is transformed to (+)-[5'α-^2H]griseofulvin (2d). Further, (-)- and (+)-dehydrogriseofulvin (1a and 3a) were subjected to the microbial transformation by seven Streptomyces species (S. roseocromogenus, S. bikiniensis, S. griseinus, S. durhamensis, S. californicus, S. fimbriatus, and S. cinereoruber), respectively, as in the case of S. cinereocrocatus and it was found that the recovered dehydrogriseofulvin is a mixture of (-)- and (+)-enantiomer as a result of isomerization and the product, griseofulvin, is mainly compose of (+)-enantiomer, except for (-)-enantiomer in the case of the fermentation of (+)-dehydrogriseofulvin by S. cinereoruber. Our results also showed that the microbial systems are effective to produce natural (+)-griseofulvin from racemic (±)-dehydrogriseofulvin, which would be a candidate as intermediates in a practical synthesis.
