Synthesis of (15E)-3 beta-hydroxyandrost-5-ene-15,17-dione 15-(O-carboxymethyl)oxime; The new hapten for 3 beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone, DHEA)

From 17 beta-hydroxy-15 beta-[(4-methoxyphenyl)methoxy]androst-5-en-3 beta-yl acetate (1) by acetylation, removal of (4-methoxyphenyl)methyl group, and oxidation with Jones reagent, 15-oxoandrost-5-ene-3 beta,17 beta-diyl 3,17-diacetate (4) was prepared. (O-Carboxymethyl)hydroxylamine treatment and subsequent diazomethane methylation gave methyl ester of corresponding 15-(O-carboxymethyl)oxime derivative. Partial acid hydrolysis gave 3-acetate as a minor product, therefore the major 17-acetate was transformed in two steps into the 3-benzoate. Oxidation at position 17 and subsequent deprotection gave for both products final (15E)-3 beta-hydroxyandrost-5-ene-15,17-dione 15-(O-carboxymethyl)oxime (14), but for 3-acetyl derivative the whole synthesis is shorter and gave higher yield.