Microbiological hydroxylation. Part XXI. Hydroxylations of 3-halogeno-17-oxo-, 3-halogeno-7-oxo-, and 17-halogeno-3-oxo-androstanes by the fungi Calonectria decora, Rhizopus nigricans, and Aspergillus ochraceus

Abstract

The hydroxylations set out in the title have been studied and the results compared with those (obtained in earlier work) of hydroxylating the parent 3-, 7-, and 17-ketones. The microbiological effect of a halogeno-substitutent depends on its nature, position, and configuration in the steroid nucleus. The 3α-fluoro-, 3α-chloro-, and 3α-bromo-5α-androstan-17-ones undergo 1β,6α-dihydroxylation with C.decora; while the 3β-chloro- and 3β-bromo-analogues are more reactive (and are also hydroxylated initially in this way), the 3β-fluoro-17-ketone is recovered essentially unchanged. Loss of halogen generally occurs during incubations of 3-halogeno-17-ketones with R.nigricans, the products being 3-oxo- and 3β-hydroxy-compounds. A.ochraceus converts the fluoro-ketones (but not the chloro-ketones) into their 11α-hydroxy- or 7β,11α-dihydroxy-derivatives; the former process has been utilised in the preparation of 3α- and 3β-fluoro-5α-androstane-11,17-dione.