Patent GB-853735-A (GB)
Title: Carboxylic acid esters of 17-alkyl-19-nor-testosterones and the manufacture thereof
IPC: C07J75/00
Filed: 1957-04-02
Abstract: The invention comprises carboxylic acid esters of 17-alkyl-19-nor-testosterones, the term alkyl including saturated and unsaturated aliphatic radicals especially those containing up to 8 carbon atoms such as the methyl, ethyl, vinyl and ethinyl radicals, and the preparation thereof by reacting a 17-alkyl-19-nor-testosterone with the required carboxylic acid or derivative thereof e.g. aliphatic or cycloaliphatic carboxylic acid or a reactive derivative thereof containing up to 11 carbon atoms. The above process may be modified that a product containing a 17-unsaturated alkyl group may be hydrogenated to form a more saturated alkyl group e.g. a 17-ethinyl group may be hydrogenated to a 17-vinyl group.  During the hydrogenation reaction, the 3-keto group may be temporarily protected by conversion to a 3-ketal group, and may be regenerated by acid treatment.  The above process may be further modified in that a starting compound is employed containing in the molecule one or more groups and/or double bonds different from those required in the end product but capable of conversion thereinto, and, after esterification as specified, and, if desired, after hydrogenation of the alkyl group in the 17-position, a remaining desired molecular conversion is carried out to form the required carboxylic acid ester.  Thus a 3-alkyl ether of 17-ethinyl-\se2:5(10)-19-norandrostendiene-3: 17b -diol may be esterified and then, if desired after previous hydrogenation of the ester thus produced to convert the ethinyl group into a more saturated group such as the ethyl group, the alkyl ether group is subjected to acid splitting with the formation of the ketone, whereby at the same time the \se5(10)-double bond is displaced into the \se4-position; or a 3-alkyl ether of 17-alkyl-\se3:5-19-nor-androstadien-3:17b -diol is esterified and then the ester thus produced converted by mild acid p  treatment into the corresponding ester of 17-alkyl-19-testosterone; or 17a -ethinyl-4-esters-3 : 17-diol may be esterified, then the ester thus produced partially hydrolysed with removal of the ester group in the 3-position, whereupon the product is partially hydrogenated and oxidised by means of an oxidising agent suitable for the conversion of a nuclear secondary hydroxy group into a keto group with the formation of the 17-ethyl-19-nor-testosterone ester.  In the examples 17-methyl-19-nor-testosterone acetate is prepared by esterifying 17-methyl-19-nor-testosterone with acetic anhydride; 17-ethinyl-19-nor-testosterone acetate, n-butyrate, n-valerate, caproate, enanthate, caprylate, and undecylate are prepared by esterifying 17-ethinyl-19-nor-testosterone in the required manner to form the corresponding 3-enol ester 17-ester, and partially hydrolysing to regenerate the 3-keto group; and 17a -vinyl-19-nor-testosterone acetate and n-butyrate are prepared by hydrogenating the corresponding 17a -ethinyl compounds.ALSO:Therapeutic compositions for oral or parenteral administration comprise carboxylic acid esters of 17-alkyl-19-nor-testosterones (the term alkyl includes saturated and unsaturated aliphatic radicals) dissolved in customary solvents, e.g. vegetable oils such as sesame, castor, cotton seed, sunflower seed and olive oils, and synthetic solvents such as glycols and lactic acid esters.