GB966099A - Novel cyclopentanophenanthrene compounds and a process for the production thereof - Google Patents

Abstract

The invention comprises 6,19-lactones of the general formulae: <FORM:0966099/C1/1> and <FORM:0966099/C1/2> (in which R represents keto, b -hydroxy or b -acyloxy and R1 represents keto, <FORM:0966099/C1/3> R2 being hydrogen or a saturated or unsaturated aliphatic hydrocarbon group of up to 8 carbon atoms), and also the 6,19-lactone of 3, 17-diketo-D 1,4-androstadien-6b -ol-19-oic acid, together with the process of preparing 19-nor-D 4-androstene-3, 17-dione by reacting a 3b , 17b -diacyloxy-6b -hydroxyandrostane with lead tetraacetate, oxidising the thus-formed 6b -, 19-oxido-3b , 17b -diacyloxyandrostane with chromium trioxide to form the lactone of 3b , 17b -diacyloxyandrostan-6b -ol-19-oic acid, treating the latter with a saponifying agent and then with a mineral acid, reacting the thus-formed 6,19-lactone of 3b , 6b , 17b -triol-19-oic acid with dihydropyran to form the 3,17-bis-tetrahydropyranyl ether of 6,19-lactone which is treated with an alkali metal hydroxide and a di-lower alkyl sulphate to form the lower alkyl ester, dehydrating the last named compound to give the ester of 3b , 17b -bis-tetrahydropyranyloxy - D 5-androsten-19-oic acid, hydrolysing the ether groups with acid, treating the product with an aluminium alkoxide in the presence of a ketone hydrogen acceptor, hydrolysing the resulting lower alkyl ester of 3,17-diketo-D 4-androsten-19-oic acid with an alkali metal hydroxide and decarboxylating the product to form 19-nor-D 4-androstene-3,17-dione. The 6,19-lactone of 3, 17-diketo-6b -hydroxy-D 1,4-androstadien-19-oic acid is prepared by dehydrogenation of the Ring A saturated analogue, e.g. with 2,3-dichloro-5,6-dicyano-1, 4-benzoquinone. The various modifications of the substitutents at C17 are achieved by standard procedures. The invention is illustrated by twenty-three detailed examples. The 3,17-diacetate of androstane-3b , 6b , 17b -triol is prepared from the 3,17-diacetate of D 5-androstene-3b , 17b -diol by treatment with perchloric acid and then N-bromo-acetamide, oxidation of the resulting 3,17-diacetate of 5a -bromoandrostane-3b , 6b , 17b -triol, debromination of the 6-keto compound produced, and finally hydrogenation of the keto group to the 6b -ol derivative. Specification 966,100 is referred to.