GB931009A - 6-methyl-19-nor-steroids - Google Patents

Abstract

The invention comprises 6a -methyl-19-norsteroids of the general formula <FORM:0931009/IV(a)/1> wherein R1 represents a hydroxy or acyloxy group, R2 represents hydrogen or a saturated or unsaturated group with 1 to 4 carbon atoms, or R1 and R2 together represent a keto group, and the preparation thereof by splitting off the 3-keto group of a D 4-3-keto-6a -methyl-19-nor-androstene substituted in the 17-position by a hydroxy or acyloxy group and a p hydrogen atom, or by a hydroxy or acyloxy group and the aliphatic hydrocarbon residue by converting the 3-keto group to a 3-thioketal group, e.g. a thioketal group derived from a thiol or a dithiol, and then removing the thioketal by reacting with an alkali metal in the presence of ammonia, or by reducing the 3-keto group to a 3-hydroxy group, esterifying or etherifying the 3-hydroxy group, and removing the resulting 3-ester or 3-ether by reacting with an alkali metal in the presence of liquid ammonia or an aliphatic primary amine. The grouping at the 17-position may be varied before or after the removal of the 3-keto group, for example, a hydroxy group at the 17-position may be esterified to form an acyloxy group such as a carboxylic acyl group, or a compound substituted solely by a hydroxy group at the 17-position may be oxidised to form a 17-keto group, and the 17-keto group may be alkylated to form compounds having the hydrocarbon group and a hydroxy group attached to the 17-position. 3-Thioketals of D 4-3-keto-6a -methyl-19-norandrostenes substituted in the 17-position by a b -hydroxy or acyloxy group and a hydrogen atom, or by a b -hydroxy or acyloxy group and a saturated or unsaturated aliphatic hydrocarbon group containing 1 to 4 carbon atoms are prepared by reacting the required free 3-keto compounds with a thiol or dithiol such as ethyl, propyl and benzyl thiol, thiophenol, and ethane, propane and butane dithiol, preferably in the presence of zinc chloride or hydrochloric acid and a dehydrating agent such as sodium sulphate, or in the presence of p-toluenesulphonic acid and an organic solvent and removing the water of reaction; by an exchange reaction; or by reacting the required free 3-ketosteroid, preferably dissolved in glacial acetic acid, with the required thiol in the presence of a Lewis acid such as boron trifluoride. Specifications 847,713 and 884,412 are referred to.