Patent GB-1014054-A (GB)
Title: New oxido-steroids
IPC: C07J71/00
Filed: 1962-09-11
Abstract: The invention comprises 2b ,19-oxido-5a -steroids of the partial formula <FORM:1014054/C2/1> (wherein R1 is two hydrogen atoms, a hydrogen atom together with a free, esterified or etherified hydroxyl group, or a free or ketalized oxo group, and R2 is a hydrogen or halogen atom or a free, esterified or etherified hydroxyl group, or R1 and R2 together represent a 3-hydrogen atom and the bivalent radical of a dibasic mineral acid, of carbonic acid or of an alkylene diol of at most 5 carbon atoms; and X is two hydrogen atoms, a hydrogen together with an iodine atom or a free or esterified hydroxyl group, or an oxo group) and the preparation thereof by treating a 2b -hydroxy-5a -steroid of the partial formula <FORM:1014054/C2/2> with a compound capable of generating monovalent positive iodine and, if desired, oxidizing a resulting 19-unsubstituted, 19-iodo or free or esterified 19-hydroxy steroid to the 2b ,19-lactone of a 2b -hydroxy-19-acid, and/or, if desired, hydrolysing any acyloxy or acetal group and/or, if desired, oxidizing any free hydroxy group to an oxo group.  The steroids may be of the androstane, pregnane, cholane, cholestane, stigmastane, spirostane or cardanolide series and may contain free, ketalized or enolized oxo groups, esterified or etherified hydroxyl groups, alkyl, alkenyl or alkynyl groups and/or halogen atoms in the nucleus or 17-side chain, or double bonds or oxido groups e.g. in positions 9 (11) or 16 (17). Iodine containing reagents are N-iodo-carboxylic acid amides or imides, iodine halides, alkyl hypoiodites prepared for example from iodine and alcohols with heavy metal oxides, and acyl hypoiodites, prepared for example from iodine and heavy metal salts of carboxylic acids e.g. iodine and lead tetra-acylates.  Resulting 19-iodo steroids may be converted to 19-unsubstituted 2b ,19-oxido steroids by treatment with bases, and these on drastic oxidation yield 2b ,19 - lactones of 2b  - hydroxy - steroid 19-acids. Other transformations which may be effected in the products of the present process are as follows: 1a -halogeno-2b ,19-oxido-17-oxo-androstanes may be reacted with hydrocarbon metal compounds to give the corresponding 17b -hydroxy-17a -hydrocarbyl compounds; a 17a - and/or 21-hydroxy group may be introduced into a 2b ,19-oxido-2p-oxo-pregnane by known methods e.g. by enol-acetylation to form the D 17(20)-20-acetate followed by peroxidation and hydrolysis to the 17a -hydroxy-20-ketone; 2b ,19-oxides containing no halogen in positions 1 and 3 may be opened hydrolytically or arylolytically e.g. with an acylating agent in presence of an acid catalyst to give 2b ,19 - diacyloxy compounds or D 1 - and D 2-19-acyloxy steroids, which may be converted into D 1-3-oxo-steroids; 2b ,19-oxides may be converted into 1a -halogeno-19-acyloxy steroids with acid halides, and the products may be converted into 1-unsubstituted D 1-compounds, particularly the 3-oxo compounds formed by hydrolysis and oxidation of 3-acyloxy compounds which may then be converted to 19-nor-steroids in known manner, if desired via 19-oxo and -carboxy steroids; 1a -halogeno-2b ,19-oxides may be opened under reducing conditions e.g. with metals and liquid ammonia or amines or with zinc in alcohol or an acid, to give D 1-19-hydroxy-steroids, and, similarly, the 19-hydroxy compounds and 2,19-lactones give D 1-19-oxo-steroids or D 1-steroid-19-acids, which, in the case of 3-oxo-steroids give, on dehydrogenation, D 1,4-3,19-dioxo-steroids or the corresponding 19-acids, which are easily decarboxylated to ring A aromatic steroids; and the acetonides or cyclic carbonates of 1a ,3a  - dihydroxy - 2b ,19 - oxidosteroids may be hydrolysed and oxidized to 1a -hydroxy - 3 - oxo - 2b ,19 - oxides, which under reductive cleavage give 19-oxygenated D -3-ketones, which may be converted to 19-nor-D 1-3-ketones. Examples are given.  1a  - chloro - 2b  - hydroxy - 3b  - acyloxy-steroid starting materials are prepared by reduction of the corresponding D 1-3-oxo-steroids, acylation of the hydroxyl group and addition of hypochlorous acid.  Cyclic 1,3-carbonate and 1,3-acetonide starting materials are prepared by reducing D 1-3-oxo-steroids to D 1-3b -hydroxy-steroids, benzoylating these, converting the benzoates by chromatography on aluminium oxide into D 1-3a -hydroxy-steroids, epoxidizing these, hydrolysing the crude epoxides with acid to 1a ,2b ,3a -trihydroxy-compounds and treating these with phosgene or acetone.  3 - Unsubstituted - 2b  - hydroxy - steroid starting materials are prepared by reduction of the 2-oxo-compounds, prepared from 3-oxo-steroids by conversion to 2-bromo-3-ketones, heating these with pyridine to give 2-pyridinium salts, oxidation of these to 2-nitrones, hydrolysis of these to 2,3-dioxo-steroids, treatment of these with tosyl chloride in pyridine to give 2-oxo-3-enol tosylates, and hydrogenation of these. Specification 994,750 is referred to.