NOVEL MICROBIAL HYDROXYLATION OF YDROXY-18,19-DINOR-17-ALPHA-PREGN-4-EN-20-YN-3-ONE

The microbial transformation of the dl and the d-enantiomer of 13-ethy l-17 beta-hydroxy-18, 19-dinor-17 alpha-pregn-4-en-20-yn-3-one (1) wer e investigated. Poor yields and poor resolutions were usually obtained for the hydroxylation reactions. Transformation of 1 by Cunninghamell a blakesleeana gave 6 beta-, 7 beta-, 10 beta-, 15 alpha-hydroxy deriv atives 4, 5, 6, 7, and 6 beta, 10 beta-dihydroxy derivative 8; transfo rmation of 1 by Cunninghamella echinulata afforded 5, 6, and 8. Biotra nsformation of the dl-1 by Cunnighamella species usually gave 10 beta- hydroxy product with the low enantiometric excess or as racemic form. However, C. echinulata was able to efficiently differentiate the two e nantiomers of 1 in the course of 6 beta, 10 beta-dihydroxylation react ions. The d-enantiomer of the dl-1 was the better substrate for this t ype hydroxylation. The 7 beta and 15 alpha-hydroxylations of 1 by mirc obial cultures was unusual for 19-nor type steroids, and these hydroxy lation reactions were presumably due to the presence of 17 alpha-ethyn yl group. (C) 1998 by Elsevier Science Inc.