Microbial hydroxylation of steroids. 8. Incubation of Cn halo- and other substituted steroids with Cn hydroxylating fungi

Abstract

A series of C-21 substituted progesterone derivatives (R = F, Cl, Br, CH3) has been prepared, and incubated the C-21 hydroxylating fungus A. niger. No biotransformation was observed where R = Cl, Br, or CH3, but a minor amount of hydroxylation occurred at an unidentified site where R = F. Two C-11β substituted progesterone derivatives (R = F, OH) were converted to the corresponding C-11 ketone by the C-11α hydroxylator R. stolonifer, but a C-11β hydroxylator (C. lunata) was unable to perform a similar transformation with a C-11α hydroxy substrate. C. lunata hydroxylated a C-11β fluoro substrate at C-14α and C-21 in low yield. C-7α and -7β-hydroxy androst-4-ene-3,17-diones were prepared and incubated with C-7β hydroxylating (R. stolonifer) and C-7α hydroxylating (M. griseocyanus) fungi respectively. No ketone formation was observed. Similarly, the C-6β hydroxylator R. arrhizus was unable to transform a C-6α-hydroxy substrate or C-6α- or C-6β-hydroxy-B-norsteroids. No oxidation at halogen was observed for any of the substrates used. 13C–19F coupling constants for 11β-fluoroprogesterone suggest the presence of through space interactions between fluorine and both C-18 and C-19.