GB883500A - Improvements in a microbiological process for the preparation of steroids and ketones - Google Patents

Abstract

Steroid compounds or aliphatic ketones are prepared by separating spores from vegetative growth material and nutrient containing fermentation medium in which the mould is grown and subjecting steroids or fatty acids to the microbiological process with the separated spores in a substantially vegetative growth material-free and nutrient-free aqueous medium, if necessary, with aeration or addition of oxygen or oxidizable material such as glucose, acetic acid or lactic acid, to form steroids which are hydroxylated or dehydrogenated in the nucleus or side chain or in which secondary alcoholic groups are dehydrogenated to keto groups or keto groups are reduced to hydroxy groups, or to form aliphatic ketones respectively. The process is particularly suitable for the preparation of an oxygenated steroid. The spores used in the above process may be obtained from vegetative cells which have been allowed to grow in submerged culture with aeration or by surface culture-particularly in the case where the organism does not sporulate or sporulate well in submerged culture, e.g. in the case of a fungus of the order Mucorales such as Rhizopus nigricans, and then the spores are harvested by first straining through cheese cloth and then through glass wool. The spores in the filtrate are recovered by centrifuging and washing with water. In the examples the following conversions are carried out using separated spores of the micro-organisms indicated: 11a -hydroxyprogesterone from progesterone using Aspergillus ochraceus; 3,20 - diketo - 17a ,21 - dihydroxy - 1,4-pregnadiene from 17a -hydroxydesoxy-corticosterone using Septomyxa affinis; and methyl vinyl ketone, methyl propyl ketone, methyl hexyl ketone and methyl heptyl ketone from octanoic hexanoic, nononoic and decanoic acids respectively using Penicillum roqueforti. The following conversions on steroids involving reduction of keto to hydroxy, dehydrogenation of secondary alcoholic groups, hydroxylation at positions 1, 2, 6, 7, 10, 11 and 12, introduction of a 1,2-double bond and side chain degradation using separated spores of the micro-organism indicated are also referred to:4-pregnene-20b -ol-3-one from progesterone using Streptomyces lavendulae; testosterone from 5-androstene-3b ,17b -diol using Proactinomyces erythropolis; estrone from estradiol using Streptomyces albus; 4-androstene-1a -ol-3,17-dione from 4-androstene-3,17-dione using Penicillium; 4-pregnene-2b ,17a ,21-triol-3,20 - dione from 4 - pregnene - 17a ,21 - diol - 3,20-dione using Streptomyces sp; 4-pregnene-6b -ol-3,20-dione from progesterone using Streptomyces aureofaciens, Aspergillus niger and Rhizopus arrhizus; 4-pregnene-7a -ol-3,20-dione from progesterone using Phycomyces blakesleanus and Peziza; 10-hydroxy-19-norprogesterone from 19-norprogesterone using Rhizopus nigricans; 4-pregnene-11a -ol-3,20-dione from progesterone using Rhizopus arrhizus; hydrocortisone from 4 - pregnene - 17a ,21 - diol using Cunninghamella blakesleeana, Curvularia lunata, Trichothecium roseum and Coniothyrium helleborine; 4-pregnene-12b -ol-3,20-dione and 4-pregnene-12b ,15b -diol from progesterone using Calnectria decora; dehydro-hydrocortisone from hydrocortisone using Streptomyces lavendulae; and 1,4-androstadiene-3,20-dione from progesterone using Streptomyces lavendulae, Fusarium solani and Fusarium caucasicum.