C-19-substituted Steroids

Steroids substituted at C-10 with carbon chains have been prepared by an apparently completely stereospecific Diels-Alder addition of but-l-en-3-one to 

3-methoxy-3,5(10)-dienes (358). The major initial adduct is the em/o-isomer (359), separable by chromatography from the minor exo-isomer, with which it can be equilibrated. Grignard reaction of the adduct with methyl magnesium iodide and subsequent treatment with acid gives the C-10 pentene (360) whilst direct treatment of the adduct with acid affords the butanone (361). 

The C-10 vinyl steroid (362) obtained by Wittig reaction on the 19-aldehyde has been converted to the 5a-bromo-6) -hydroxy-derivative which, on oxidation with lead tetra-acetate, produced the 19-methylene-6, 19-oxide which was then reduced quantitatively by zinc-acetic acid to the 10j8-acetyl compound (363). An analogous 10) -acetyl compound (364), whose formation involves a 1,5-hydride shift, was obtained along with some of the desired 19-hydroxy-19-methyl steroid on attempted base hydrolysis of the 19/ -19-acetoxy-19-methyl-androstanedione (343). The main product of the reaction however, was the ketal (365), or, if the reaction mixture was neutralised before work up, the hemi-acetal 

Similar treatment of the methanesulphonate (367 R = OMs) afforded only the products of substitution (367 R = OAc) and (369) in equal amounts. 

19-epoxydienone (372) has been prepared by the action of acid or base upon either the fluoro- or chloro-19-acetates (371), which were obtained by halogenation of the oxalyl derivative of (370) and subsequent cleavage of the 6/5,19-oxide ring with acetic anhydride-toluene-p-sulphonic acid. 

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N.m.r. has been used for assignment of configuration to 5a-cholest-8(14)-ene-3/3,7a,15a-triol and related compounds with allylic hydroxy-groups/ and H n.m.r. studies have been applied to some C-19 substituted steroids and b/S-CHaX-substituted 19-nor-5(10)-enes, to evaluate a-, p, 7-, and 5-substi-tuent effects and obtain information on the rotameric populations of substituted methyl groups. Other authors report shift data for some 19-hydroxy-, 5,6-epoxy-, A -3-oxo-, and 24-ethyl steroids. The incorporation of and from labelled ethanol into cholic acid in rats has been studied by high-resolution mass spectrometry and n.m.r, ... 

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