GB1182257A - 03-Alkyl-21-Hydroxy-18,19-Dinorpregn-4-Ene-3,20-Diones and Derivatives Thereof - Google Patents

Abstract

1,182,257. 13 - Alkyl - 21 - hydroxy - 18,19- dinorpregn - 4 - ene - 3,20 - diones. H. SMITH. 16 May, 1967 [19 May, 1966], No. 22342/66 Heading C2U. Novel steroids of the formula (wherein R<SP>1</SP> is C 2-4 n-alkyl; R is H or acyl; and X is acyloxymethylene, hydroxymethylene or carbonyl), alone or in admixture with their 13α-entantiomers, are prepared (1) from the corresponding 17-acetyl or -halocarbonyl steroids by standard procedures; or (2) from corresponding steroids containing in ring A a protected 3-keto group together with appropriate double bonds by hydrolysis. Process (1) may be effected (a) by converting a 17-halo. carbonyl steroid to the 21-diazo-pregnen-20-one and hydrolysing or acylolysing this to the required 20-on-21-ol or its acylate, the halocarbonyl steroid being prepared in turn by converting by a Wittig reaction the corresponding 3 - alkoxy - gona - 1,3,5(10) - trien - 17 - one to the corresponding 17-methylene compound, hydroborating this to the 17-hydroxy-methyl compound, oxidizing this to the 17-carboxy compound, reducing in ring A by the Birch method to give the corresponding gona-2,5(10)- diene and hydrolysing this to the gon-4-en-3- one, and halogenating the 17-carboxy group; or (b) by converting a 17-acetyl steroid to the haloacetyl compound and acylolysing to give the required 21-acyloxy-pregnen-20-one; or (c) by converting the 17-acetyl steroid to the 21-ethoxalyl derivative, halogenating this and acylolysing the product to give a product as in (b). Starting materials for process (2) are desirably 3-alkoxy-pregna-2,5(10)-dienes, prepared by Birch reduction of the pregna-1,3,5(10)- triene-20,21-diols or 20-on-21-ols or mono- or di-acylates thereof, the 20,21-diols being in turn prepared by ethoxyethynylating the appropriate gona- 1,3,5(10)-trien-17-ones, either hydrogenating and acid treating the thus-produced 21- ethoxy - 17α - pregna - 1,3,5(10) - trien - 20 - ynols to give the corresponding pregna-1,3,5(10), 17(20)-tetraen-21-ones and reducing these to the 21-ols or acid treating the 21-ethoxy-20-yn-ols to give 17-carboxymethylene compounds and reducing these to the 21-ols, and then tetrahydropyranylating these and hydroborating the products. The starting materials for process (2) may also be prepared by methods similar to those detailed under (a), (b) and (c) above. 17-Hydroxy or acyloxy-acetyl products may be reduced to the 21-ols and any of these compounds may be acylated or hydrolysed as appropriate. Specification 1,115,635 is referred to. The steroids of the invention, which have mineralo-corticoid or other steroid hormone activity, may be made up into pharmaceutical compositions with suitable carriers.