Norsteroids by Total Synthesis

Steroids not readily accessible by modification of plant starting materials, for example, those possessing unusual substituents at the angular positions, are made available by total synthesis. 

It is probable, too, that intensive-process research development on the reactions involved in these syntheses may have made these routes commercially competitive with partial syntheses based on plant sterols. 

In the first of these sequences, often called the Torgov-Smith synthesis, the initial step consists in condensation of a 2-alkyl-cyclopentane-l,3-dione with the allyl alcohol obtained from 6-methoxy-l-tetralone and vinylmagnesium chloride. Although this reaction at first sight resembles a classic SN displacement, the reaction is actually carried out with only a trace of base. 

As with the other sex hormones, the first clinical use of Hiidrogens was for support therapy in individuals deficient in the endogenous hormone. The discovery that androgens exert an ana-hnlic effect greatly extended the indications for their use. 

Reaction of estrone methyl ether with methyl Grignard reagent followed by Birch reduction and hydrolysis of the intermediate enol ether affords the prototype orally active androgen in the 19-nor series, normethandrolone (69). ° (Note that here again the addition of the methyl group proceeded stereoselectively by approach from the least hindered side.) The preparation of the ethyl homolog starts by catalytic reduction of mestranol treatment of the intermediate, 70, under the conditions of the Birch reduction and subsequent hydrolysis of the intermediate enol ether yields norethandrolone (71).  

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