GB843218A - Production of pregnadienes - Google Patents

Abstract

An 11-hydroxylated derivative of 1,4-pregnadiene-17 a ,21-diol-3,20-dione or a 21-acyloxy ester thereof is prepared by subjecting 1,4-pregnadiene-17 a ,21-diol-3,20-dione or a 21-acyloxy ester thereof to the action of an enzyme of a micro-organism known to be capable of 11-hydroxylating a pregnene compound which is saturated and unsubstituted at the 11-position. The process may include an additional step of oxidising the resulting 11-hydroxy compound in the form of its 21-acloxy ester to an 11-keto compound. 1,4-Pregnadienes containing a 21-ester group prepared by the above process may be hydrolysed to the free 21-hydroxy compounds. The pregnadiene may be 11 a -hydroxylated e.g. by the action of any one of the micro-organisms Rhizopus urrhizus, R. delmar, R. nigricans, R. reflexus, Aspergillus niger or Phycomycers blakesleeanus, or may be 11b -hydroxylated e.g. by the action of the micro-organism Cunninghanella blakesleena or Curvularia lunata. A suitable 21-acyloxy ester is the 21-acetate but the acyloxy group may also be derived from propionic, butyric, valeric or succinic acid, or an aromatic acid such as benzoic, salicylic phthalic or veratric acid. The oxidation &c., may be carried out with chromic acid in pyridine. In the examples:-(1) 1,4-pregnadiene-11 a ,17 a ,21-triol-3,20-dione is prepared by the action of a culture of R. nigricans on 1,4-pregnadiene-17 a ,21-triol-3,20-dione, and is then acetylated to form the corresponding 21-acetate and the 21-acetate is oxidised and then hydrolysed to form 1-dehydrocortisone acetate and 1-dehydrocortisone respectively; (2) 1,4-pregnadiene-11 b ,17 a ,21-triol-3,20-dione is prepared by the action of a culture of C. lunata on 1,4-pregnadiene-17 a ,21-diol-3,20-dione and is oxidised as in (1).