GB792803A - Oxidation products from compounds of the steroid series and process of making same - Google Patents

Abstract

The invention comprises a process for the manufacture of oxidation products from compounds of the steroid series, wherein saturated and unsaturated compounds of the pregnane or androstane series which contain in the 3,20- or 3,17-positions respectively a free or protected hydroxyl or oxo group, are brought into contact with enzymes produced by a culture of fungi of the species Fusarium solani, Fusarium caucasicum and Rhizopus suinus, and the saturated or unsaturated androstanes which contain in the 3- and 17-positions free or protected hydroxyl or oxo groups or saturated or unsaturated testolactones formed are isolated. The invention also comprises the compound 1:2-dihydrotestolactone <FORM:0792803/IV (b)/1> melting at 219 DEG to 220 DEG C. and having the specific rotation <FORM:0792803/IV (b)/2> (c=1.025 in chloroform); ultra-violet absorption maximum at 242 mm (log e =4.23). As starting materials there may be used, for example, progesterone, or 11-dehydro-, 11-keto- or 11-, 12-, or 14-hydroxyprogesterones, D 5- or D 4-pregnene-3-ol-20-ones, D 5-pregnene-3:20-diols, 11-desoxycorticosterone, corticosterone, 11-dehydro-corticosterone, D 4- or D 5-androstene-3:17-dione, testosterone, D 5-androstene-3-ol-17-one, adrenosterone, pregnane-3:20-dione, pregnane-3-ol-20-one, androstane - 3:17 - dione, allopregnane - 3:20 - dione, 3b - acetoxy - allopregnane - 20 - one and corresponding compounds with protected hydroxyl or oxo groups. There may also be present double bonds in the 4-, 5-, 6-, 7-, 8-, 9:11-, 11- or 14-position or additional substituents such as free or protected hydroxyl, oxo or carboxyl groups, or epoxy groups or halogen atoms, for example in the 4-, 5-, 6-, 7-, 8-, 9-, 11-, 12-, 14- or 21-position. In examples: (1) progesterone is added to a nutrient medium which has been previously inoculated with a culture of Fusarium solani and allowed to grow. After 48 hours further standing at 25 DEG C. and filtration there is recovered and purified by chromatography the compound D 1:4-androstadiene3:17-dione. Fusarium caucasicum may replace the Fusarium solani in a similar process. 11 - Desoxy - corticosterone or D 4- androstene-3:17-dione may be used in place of progesterone; (2) D 5-androstene-3b -ol-17-one is prepared by a similar process from D 5-pregnene-3b -ol-20-one; (3) D 1:4-androstadiene-3:17-dione is obtained, using a similar culture of Fusarium solani, from a neutral portion containing chiefly D 4-androstene-3:17-dione and progesterone obtained by the chromic acid oxidation of cholesteryl-acetate dibromide followed by debromination, hydrolysis and dehydrogenation by the method of Oppenauer; (4) D 1:4-androstadiene-3:17-dione is added to a previously prepared culture of Fusarium caucasicum and after 7 days incubation there is recovered from the filtrate 1:2-dehydro-testolactone. This compound can also be obtained from progesterone, D 5-pregnene-3:20-dione, D 4 - pregnene - 3b - ol - 20 - one, 11 - desoxy - corticosterone or D 4-androstene-3:17-dione, using conditions similar to those of Example (1) but extending the incubation period to 6 to 10 days; (5) to three separate cultures of Fusarium solani in nutrient medium there is added allopregnane-3:20-dione, the cultures then being incubated for 1, 2 and 7 days respectively. Extracts of the first two yield androstane-3:17-dione and that of the third yields D 1:4-androstadiene-3:17-dione. Treatment of 3b -acetoxy - allopregnene - 20 - one yields similar products. Similar treatment of androstane-3:17-dione yields unchanged starting material after 1 and 2 days and D 1:4-androstadiene-3:17-dione after 7 days; (6) 11-desoxy-corticosterone is added to a culture of Rhizopus suinus in nutrient medium and from the mixture after 6 days' incubation there is recovered testolactone; (7) progesterone is added to portions of the mycelia recovered from the growth of Fusarium solani in nutrient medium. After 36 hours incubation at 26 DEG C. 1:4-androstadiene-3:17-dione is recovered. After 7 days incubation the product is 1:2-dehydrotestolactone. Specification 724,094 is referred to.