Steroids

Abstract

The numerous patents listed in Table I issued during 1962 indicated increasing sophistication in carrying out steroid transformations by using such techniques as cell-free enzyme systems, simultaneous and consecutive use of more than one microorganism, and the use of mold spores in a nongerminating environment. These techniques undoubtedly are being used in some commercial applications. The entire field of microbial transformations of steroids was surveyed32 in a review with 172 refs. 1,2-DehydrogenationMycobacterium jlavum was the fastest dehydrogenating strain of 248 strains from the genera Fusarium, Streptonayces, Nocardia, and Mycobacterium examined.* Further examination indicated that 17a-hydroxylation with side-chain cleavage at this position also occurred.? Other reports of 1,2-dehydrogenation include A4;3-0x0 steroids by Volutella ciliata, Ramularia robusta, and Hypomyces solani39 and 11/3,21-dihydroxy-4,17(2O)-pregnadiene-3-one by Septonzyxa a f l n i~.~~" A kinetic study of the dehydrogenation using enzymes isolated from Septomyxa aflnis indicated that the reaction was product inhibited.12 Dehydrogenation of 16&methyl-5a-dehydrocortisone to 16B-methyl prednisolone was carried out by Corynebacterium simple^.^^^ Compound S was dehydrogenated by Stereunz fasciaturn to yield 17a,20/3,21-trihydroxy-l,4-pregnadiene-3-one, and 17a-methyl-testosterone was also converted to its corresponding 1,2dehydrogenated deri~ative.6~ An Actinoplanes species converted dehydroepiandrosterone to androsta-1,4-diene-3,17-dione and prolonged contact was followed by 6a-and GP-hydro~ylation.~~ -HydroxyIationA process for 1 l-hydroxlation of 17 a-hydroxycortexone using Absidia orchidis and the separation of both ll-epimers was described.2fiFifty per cent conversion yields of Compound S to hydrocortisone by Curvularia lunata were reported for pilot scale studies.YO A variety of hallucinogenic fungi were shown capable of 11 a-hydroxylating Compound S when grown submerged.'* In a study of the progesterone transforming characteristics of 191 strains of Penicillium, 11 a-hydroxylation, 15P-hydroxyIation, and side-chain cleavage were the three main transformations indicated.6