Patent GB-1014657-A (GB)
Title: Process for the manufacture of new oxido-steroids
IPC: C07J75/00
Filed: 1962-09-24
Abstract: 4b ,19-oxido-steroids are prepared by oxidizing 19-unsubstituted 4b -hydroxy-5a -steroids with lead tetra-acylate in a solvent and, if desired, the products are oxidized to 4b ,19-lactones of 4b -hydroxy-steroid 19-acids and/or any acyloxy groups present in the products are hydrolysed, and, if desired, resulting hydroxy compounds are oxidized to the corresponding ketones.  The starting material, which may be of the pregnane, androstane, cholane, cholestane, stigmastane, spirostane or cardanolide series, may contain in the 3-position two hydrogen atoms, a hydrogen atom and an etherified or esterified hydroxyl group or a ketalized oxo group and in the 5-position a hydrogen or halogen atom or an etherified or esterified hydroxyl group or the radical of a dibasic acid or of a lower aliphatic or araliphatic diol attached to the 3- and 5-positions, e.g. cyclic carbonates, sulphites, acetonides and benzal compounds, as well as free, ketalized or enolized oxo groups, esterified or etherified hydroxyl groups, alkyl or alkenyl groups or halogen atoms, double bonds, and oxido groups at other positions of the steroid nucleus or 17-side chain.  4a ,9a -oxido-5b -steroids may be obtained as by-products, and separated by chromatography.  In examples: (1) D 4 - 17b  - propionyloxy - androstene is nitrated to D 4 - 4 - nitro - 17b  - propionyloxyandrostene this is reduced to 4-oxo-17b -propionyloxy - 5a  - androstane, this is hydrogenated to 4b -hydroxy-17b -propionyloxy-5a -androstane, and this is oxidized by the process of the invention to the 4-oxo-compound (10%), 4a ,9a  - oxido - 17b  - propionyloxy - 5b  - androstane (15%) and the required 4b ,19-oxido-17b -propionyloxy - 5a  - androstane; (2) D 4 - 3 - oxo-20b  - acetoxy - pregnene is converted to the 3-thioketal, this is acetylated, desulphurized and reacted with N-bromosuccinimide to give 4b -hydroxy - 5a  - bromo -20b  - acetoxy - pregnane, this is oxidized by the process of the invention to 4 - oxo - 5a  - bromo - 20b  - acetoxy - pregnane (5%) and the required 4b ,19-oxido-5a -bromo-20b -acetoxy-pregnane which on reduction gives D 4 - 19 - hydroxy - 20b  - acetoxy - pregnene, which by oxidation, hydrolysis and further oxidation gives 19-nor-progesterone; (3) the product of (1) is oxidized to the 4b ,19-lactone of 4b -hydroxy-17b  - propionyloxy - 5a  - androstane 19 - acid; and (4) 3b ,17b  - diacetoxy - 4b  - hydroxy - 5a  - chloro - androstane is oxidized by the process of the invention to 3b ,17b -diacetoxy-4b ,19-oxido-5a -chloro -androstane, this is hydrolysed to the corresponding diol, this is oxidized to the corresponding dione, and this is reduced to D 4 - 3,17 - dioxo - 19 - hydroxy - androstene; also, the product of (1) is reacted with acetic anhydride and p-toluene-sulphonic acid to give D 4 - 19 - acetoxy - 17b  - propionyloxy-androstene, this is converted to D 4 - 17b ,19 - dihydroxy - androstene, this is oxidized to D 4 - 17 - oxo-androstene-19-acid and this on slow vacuum distillation yields D 5(10)- 17 - oxo - 19 - nor - androstene, used for the preparation of the corresponding 17b  - hydroxy - 17a  - hydrocarbon compounds.  Some of these processes are referred to in more general terms, and the preparation of 4b -hydroxy steroids by hydrolytic cleavage of 4,5-epoxides is also mentioned.