Patent GB-1045856-A (GB)
Title: 10ª-steroids and process for their manufacture
IPC: C07J75/00
Filed: 1963-07-08
Abstract: D 4-, D 1,4- and D 5-3-oxo-10a -methyl -steroids are prepared by (a) hydrogenating D 3-2-oxo -1,5b -cyclo-10a -methyl-steroids to give the corresponding 3,4-saturated steroids; (b) treating these with a strong acid in presence of an acylating agent to form the enol-acylates of the corresponding 5a aacyloxy-2-ketones (D 1-2,5a -diacyloxy-10a -methyl-steroids), or (c) treating the products of (a) with a strong acid in the absence of an acylating agent to form the corresponding D 5-2-ketones; (d) hydrolysing the products of (b) with an aqueous acid to form the corresponding 5a -acyloxy-2-ketones, or(e) oxidizing the products of (b) with selenious acid or a derivative thereof to form the corresponding D 4 - 2 - acyloxy - 3 - oxo - 10a  - methyl-steroids; (f) or (g) reacting the products of (c) or (d) with a lead tetra-acylate in a solvent in the presence of a strong acid to form the products of (e); (h) heating these last-named products with zinc in a solvent to give the required 2 - unsubstituted D 4 - 3 - oxo - 10a  -methyl-steroids; and, if desired, (i) converting these into the corresponding D 5-steroids by irradiation with ultra-violet light in an inert solvent or dehydrogenating them in the 1,2-position to give the corresponding D 1,4-steroids by known methods and/or liberating any esterified hydroxyl groups and/or oxidizing any free hydroxyl groups to keto groups. Products of the pregnene and androstene series are novel steroids, and products of other series, e.g. the cholene, cholestane, spirostane and cardanolide series, may be converted to them by known methods.  All the above-mentioned starting materials, intermediates and final products are stated to have the "normal" configurations in the 8- and 9- positions, i.e. 8b  and 9a . Strong acids for use in (b) or (c) include anhydrous mineral acids, sulphonic acids, and Lewis acids, process (c) is preferably effected in solution in a lower aliphatic carboxylic acid, and process (b) is advantageously effected with anhydrides or halides of lower aliphatic carboxylic acids. Aqueous acids for use in step (d) are preferably mixtures of lower aliphatic carboxylic acids with water in the presence of small amounts of mineral acids. Saponification of the products of (e) gives D 4-2-hydroxy-3-oxo-10a -methyl-steroids. 17 - Oxo - androstane products may, after the D 4-3-oxo group has been protected, be converted to the corresponding 17a -(alkyl, alkenyl or alkynyl)-17b -hydroxy products.  The starting materials may contain in one or more of positions 7, 8, 9, 11, 12, 14, 15, 16 and 17 and in the 17-side chain lower alkyl groups, halogen atoms, free, esterified or etherified hydroxyl groups and/or carbalkoxy groups.  D 3 - 2 - oxo - 1,5b  -cyclo - 10a  - methyl -steroids are prepared by irradiation of D 1,4-3-oxo-steroids with ultra-violet light followed by chromatographic separation.  The novel 10a -methyl steroids referred to above, which are stated variously to exhibit anti-androgenic, ovulation-inhibiting and gestagenic activity, may be made up into pharmaceutical compositions suitable for parenteral, enteral or topical administration with suitable carriers.  The compositions may contain preserving, stabilizing, wetting or emulsifying agents, salts for regulating the osmotic pressure, or buffers.