GB994747A - 19-oxygenated steroids and process for their manufacture - Google Patents

Abstract

The invention comprises D 5-3-hydroxy- or -acyloxy-steroids of the androstane, pregnane or spirostane series containing in the 10-position a hydroxymethyl, acyloxymethyl, formyl, carboxy or carbalkoxy group; and a process for the preparation of any steroid containing a D 5-double bond and the aforementioned 3- and 10-substituents wherein a 5a -halogeno-6b , 19-steroid, a 19,6b -lactone of a 5a - halogeno - 6b - hydroxy - steroid 19 - acid or a 19,6b -cyclohemiacetal of a 10-formyl-5a -halogeno - 6b - hydroxy - steroid is treated with a reducing agent and, if desired, any hydroxy or 10-carboxy compound obtained is esterified or any hydroxy or 10-formyl compound obtained is oxidized and/or any ester obtained is hydrolysed. The starting material may belong to any of the steroid series mentioned above or to the cholane, cholestane, stigmastane or cardanolide series, and may contain free, ketalized or enolized oxo groups, esterified or etherified hydroxyl groups, alkyl groups of at most 7 carbon atoms or halogen atoms in one or more positions of the steroid nucleus or 17-side chain. They may also contain double bonds and oxido groups. When alkali or alkaline earth metals in liquid ammonia are used as reducing agents D 5-19-hydroxy-steroids are formed, and this may be accompanied by the reduction of other oxido groups or of oxo groups unless they have previously been protected. 19,6b -hemiacetals of 5a -halogeno-6b -hydroxy - 19 - oxo - steroids and 19,6b - lactones of the corresponding 19-acids can be reduced under mild conditions e.g. the use of zinc and an alcohol or an acid, to yield, respectively, D 5-19-oxo-steroids and D 5-steroid-19-acids. These may also be prepared by oxidation of the 19-hydroxy-steroids. The steroids of the invention may further be converted to 19-oxygenated D 4 - 3 - oxo - steroids and these may then be heated with an alkali metal hydroxide in an anhydrous or aqueous solution to give 19-nor - D 4 - 3 - oxo - steroids. Examples are given and an extensive list of esterifying acids is provided. The 19,6b - lactone of 3b - acetoxy - 5a -chloro - 6b - hydroxy - 17 - oxo - androstane - 19-acid is prepared by chromic acid oxidation of the corresponding 6b ,19 - oxido compound. Specifications 994,764, 994,748 and 994,750 are referred to.