GB991473A - New steroid compounds, processes for their production and their conversion into therapeutically-valuable substances - Google Patents

Abstract

The invention comprises 3b ,20b -dihydroxy-8b - methyl - 5a - pregn - 9(11) - en - 7 - one and its 3b - and/or 20b -esters and processes for the preparation thereof in which a 20b -aroyloxy-pregn-4-ene-3,11-dion of the formula <FORM:0991473/C2/1> (where RO designates an aroyloxy group) is esterified in enol form at the 3-position by reaction with an acylating agent derived from a lower organic carboxylic acid (1-6 carbon atoms) to form the corresponding 3-acyloxy-20b - aroyloxy - pregna - 3,5 - dien - 11 - one which is then reduced and saponified at the 3-position to form the corresponding 20b -aroyloxy - 3b - hydroxy - pregn - 5 - en - 11 - one, which compound is then re-esterified at the 3-position by reaction with an acylating agent derived from a lower organic carboxylic acid to form the corresponding 3-acyloxy-20b -aroyloxy - pregn - 5 - ene - 11 - one, which is then reacted with an oxidizing agent for steroids and thus oxidized at the 7-position yielding the corresponding 3b -acyloxy-20b -aroyloxy - pregn - 5 - en - 7,11 - dione, which is catalytically hydrogenated forming the corresponding 3b - acyloxy - 20b - aroyloxy - 5a - pregn-7,11-dione, which after protection of the 7-keto group is reduced at the 11-position forming the corresponding 7-ketal of a 3b -acyloxy - 20b - aroyloxy - 11b - hydroxy - 5a -pregnan-7-one which is then dehydrated, thus forming the corresponding 7-ketal of a 3b -acyloxy - 20b - aroyloxy - 5a - pregn - 9(11)-en-7-one the protected 7-keto group of which is then liberated to form the corresponding 3b -acyloxy - 20b - aroyloxy - 5a - pregn - 9(11) - en-7-one, which compound is then reacted with a methylating agent, resulting in the introduction of an 8b -methyl group and yielding the corresponding 3b - acyloxy - 20b - aroyloxy - 8b -methyl - 5a - pregn - 9(11) - en - 7 - one. The reduction and saponification may be effected with sodium borohydride, the oxidation with a chromic ester, the catalytic hydrogenation using palladinized charcoal, the dehydration with methane sulphonyl chloride in pyridine and the methylation with methyl iodide in the presence of potassium tert-butylate in tert-butanol. Subsequently 8b -methyl-D 1-cortisone may be obtained in a process in which 3b ,20b -dihydroxy - 8b - methyl - 5a - pregn - 9(11)-en-7-one is reduced at 7-position by treatment with anhydrous hydrazine resulting in the formation of 3b ,20b -dihydroxy-8b -methyl-5a -pregn-9(11)-ene, which is then hydroxylated at the 11a -position by reacting it with diborane in the presence of ether for a limited time followed by oxidation, resulting in the formation of 3b ,11a ,20b -trihydroxy-8b -methyl-5a -pregnane, which is then oxidized to form 8b - methyl - 5a - pregnan - 3,11,20 - trione, the 3-keto group of which is protected by ketalization resulting in the formation of a 3-ketal of 8b - methyl - 5a - pregna - 3,11,20 - trione, which is then reacted with oxygen in the presence of an alkali metal alcoholate, thus forming a 17a -hydroperoxy derivative which is reduced and hydrolysed to form the 17a -hydroxy - 8b - methyl - 5a - pregna - 3,11,20-trione, into which by successive bromination and dehydrobromination there are then introduced double bonds at the 1- and 4-positions forming 17a - hydroxy - 8b - methyl - pregna-1,4-diene-3,11,20 -trione which is then reacted with iodine in alkaline medium and the resultant compound is then acyloxylated to form the corresponding 21-acyloxy-17a -hydroxy-8b -methyl - pregna - 1,4 - dien - 3,11,20 - trione which if desired, is saponified at the 21-position and optionally re-esterified. Specifications 991,474, 991,475 and 991,476 are referred to.