Patent GB-785018-A (GB)
Title: Hydroxyl compounds of the steroid series and the preparation thereof
IPC: A61M15/06
Filed: 1953-01-16
Abstract: The invention comprises 7,8,9,11-tetrahydroxy-steroids having at rings B and C the structure: <FORM:0785018/IV (a)/1> and 7-keto-9,11-dihydroxy-steroids having at rings B and C the structure: <FORM:0785018/IV (a)/2> and processes for the preparation thereof by treating 7,11-dihydroxy-8,9-oxido-steroids having at rings B and C the structure: <FORM:0785018/IV (a)/3> in a substantially non-anhydrous medium with an acidic agent of the Lewis type to form a 7-keto-9,11-dihydroxy steroid having the above structure or with an inorganic in a medium containing a substantial amount of water in order to hydrolyse the oxido group to form a 7,8,9,11-tetrahydroxy-steroid having the above structure and, if desired, this compound may be treated with an acidic agent of the Lewis type to form a 7-keto-9,11-dihydroxy-steroid having the above structure.  The acidic agent of the Lewis type may be an inorganic acid as well as a compound which does not have a hydrogen atom replaceable by a metallic ion, e.g. boron trifluoride and zinc chloride-preferably used in an anhydrous organic solvent.  These acidic agents may be used in an anhydrous medium, but if inorganic acids such as hydrobromic acid of high concentration are used, small amounts of water relative to the amount of acid present do not alter the course of the reaction. It is preferable to use concentrated hydrobromic acid in glacial acetic acid.  Dilute inorganic acids such as dilute sulphuric acid in an organic solvent are preferred for the formation of the 7,8,9,11-tetrahydroxy-steroids.  The 7,11-dihydroxy-8,9-oxido-steroid reactant may be an ergostane, cholestane, coprostane, sitostane, stigmastane, spirostane, cholane, allocholane, pregnane, androstane or aetiocholane derivative.  In addition, the reactant may be substituted in the nucleus or in the side chain, particularly in the 3-, 5-, 6-, 17-, 20- and/or 21-positions by free or functionally converted hydroxyl or oxo groups, e.g. acyloxy groups such as acetoxy, propionyloxy, benzoyloxy and tosyloxy groups, alkoxy groups such as methoxy and ethoxy groups, and acetalized oxo groups, by free or functionally converted carboxyl groups such as nitrile and esterified carboxyl groups and a lactone group as exemplified by the butenolide group.  The preferred compounds of the invention are 7,8,9,11-tetrahydroxysteroids having the above structure and having in position 3 a free or functionally converted hydroxyl or oxo group.  In the examples: (1) D 22:23 - 3b - acetoxy -7,8,9,11 - tetrahydroxyergostene is prepared by treating D 22:23-3b  - acetoxy - 7,11 - dihydroxy - 8,9 - oxidoergostene with a mixture of glacial acetic acid, dioxane and a small quantity of dilute sulphuric acid; (2) D 22:23 - 3b  - acetoxy - 7 - keto - 9,11 - dihydroxy-ergostene is prepared by treating D 22:23 - 3b  - acetoxy - 7,11 - dihydroxy - 8,9-oxido - ergostene with boron trifluoride - ether complex in benzene; the semicarbazone and the 3b ,11-diacetoxy derivatives of the D 22:23-3b  - acetoxy - 7 - keto - 9,11 - dihydroxyergostene are also prepared; (3) D 22:23-3b -acetoxy - 7 - keto - 9,11 - dihydroxy - ergostene is prepared by treating D 22,23 - 3b  - acetoxy-7,11 - dihydroxy - 8,9 - oxido - ergostene with glacial acetic acid and dilute sulphuric acid and with glacial acetic acid and concentrated hydrobromic acid; (4) D 22:23 - 3b  - acetoxy-7 - keto - 9,11 - dihydroxy - ergostene is prepared by treating D 22:23 - 3b  - acetoxy-7,8,9,11 - tetrahydroxy - ergostene with glacial acetic acid and concentrated hydrobromic acid; (5) 3b ,17b  - diacetoxy - 7 - keto - 9,11 - dihydroxy-androstane is prepared by treating 3b ,17b - diacetoxy - 7,11 - dihydroxy - 8,9-oxido - androstane as in (2). The 7 - keto-9,11-dihydroxy-steroids having the above structure may be converted into D 8:9 - 7 - keto - 11 - hydroxy-steroids by the action of alkali, and in the examples D 8:9,22:23-3b ,11-dihydroxy-7-ketoergostadiene is prepared from D 22:23-3b -acetoxy - 9,11 - dihydroxy - 7 - keto - ergostene, D 8:9,22:23 - diacetoxy - 7 - keto - ergostadiene is prepared from D 22:23-3b -acetoxy-7-keto-9,11-dihydroxy - ergostene, and D 8:9-3b ,11a ,17b -trihydroxy - 7 - ketoandrostene is prepared from 3b ,17b  - diacetoxy - 7 - keto - 9,11 - dihydroxy-androstane and is converted into D 8:9-3b ,11a ,17b  - triacetoxy - 7 - keto - androstene Starting compounds.  7,11-Dihydroxy-8,9-oxido-steroids having the above structure are prepared by treating D 8:9-unsaturated steroids, which contain in positions 7 and 11 free or functionally converted hydroxy groups, with oxidizing agents, e.g. chromium trioxide or organic or inorganic peracids.  In the examples: D 22:23-3b  - acetoxy - 7,11 - dihydroxy - 8,9 - oxido ergostene is prepared by treating D 8:9,22:23-3b  - acetoxy - 7,11 - dihydroxy - ergostadiene with monoperphthalic acid or with chromium trioxide in glacial acetic acid, and 3b ,17b -diacetoxy - 7,11 - dihydroxy - 8,9 - oxido - androstane is prepared by treating D 8:9-3b ,17b -diacetoxy - 7,11 - dihydroxy - androstene with monoperphthalic acid.