Novel microbial hydroxylation of 13-ethyl-17 beta-hydroxy-18,19-dinor-17 alpha-pregn-4-en-20-yn-3-one

The microbial transformation of the dl and the d-enantiomer of 13-ethyl-17 beta-hydroxy-18,19-dinor-17 alpha-pregn-4-en-20-yn-3-one (1) were investigated. Poor yields and poor resolutions were usually obtained for the hydroxylation reactions. Transformation of 1 by Cunninghamella blakesleeana gave 6 beta-, 7 beta-, 10 beta-, 15 alpha-hydroxy derivatives 4, 5, 6, 7, and 6 beta,10 beta-dihydroxy derivative 8; transformation of 1 by Cunninghamella echinulata afforded 5, 6, and 8. Biotransformation of dl-1 by Cunninghamella species usually gave 10 beta-hydroxy product with the low enanitomeric excess or as the racemic form. However, C. echinulata was able to efficiently differentiate the two enantiomers of 1 in the course of 6 beta,10 beta-dihydroxylation reactions. The d-enantiomer of the dl-1 was the better substrate for this type hydroxylation. The 7 beta and 15 alpha-hydroxylations of 1 by microbial cultures was unusual for 19-nor type steroids, and these hydroxylation reactions were presumably due to the presence of 17 alpha-ethynyl group.