The microbiological hydroxylation of steroids and related compounds.

The factors which determine the specific positions at which steroids are hydroxylated by micro-organisms are being investigated, using mono-ketones or keto-alcohols of the androstane series as substrates and infra-red and n.m.r. spectroscopy to determine the structures of the products. Whereas the major product of the hydroxylation of 5o-androstan-3-one by cultures of Calonectria decora is 123,l5x-dihydroxy-5eL-androstan-3-one, by contrast, with the 17ketone as substrate, I I,6oc-dihydroxylation occurs. The hydroxyl groups introduced are on centres about 4 A apart and at distances from the carbonyl 'directing' group which are approximately comparable. With a range of other substrates and with several other organisms results of a similar nature are obtained, revealing the dependence of the substitution pattern on the position of the oxygen function(s) of the substrate. The regio-specific reactions of organic compounds are usually associated with the presence of functional groups. Substitution is facilitated by bond polarization, i.e. the presence of a good leaving group or of adjacent activat.ion. Substitution at remote sites can only be achieved by transmitting these effects by appropriate means. The organic chemist has become very ingenious at this, constructing scaffolding enabling him to activate remote positions. In recent years, however, we have seen developments in what is now referred to as 'the functionalization of unactivated carbon'. The first instance was the quite unexpected transannular substitutions1 observed independently in medium-sized rings by Cope and Prelog. The Barton reaction2, initially demonstrated with steroidal 20-nitrites, is both of great practical value and of theoretical interest. It made aldosterone (II) available in just three steps from the relatively accessible corticosterone (I) and, in my view,