Synthesis of (19E)-3β,7α-dihydroxy-17-oxoandrost-5-en-19-al 19-( O-carboxymethyl)oxime, a new hapten for 7α-hydroxydehydroepiandrosterone(3β,7α-dihydroxyandrost-5-en-17-one)

Abstract

The title compound was prepared in 11 steps from 17,17-ethylenedioxy-19-hydroxyandrost-5-en-3β-yl acetate. After tert-butyldimethylsilyl protection of the 19-hydroxyl group, a 7-oxo group was introduced by oxidation with 3,5-dimethylpyrazole-chromium trioxide complex, and then selectively reduced with l-Selectride® to give a 7α-hydroxy derivative. This partially protected triol was acetylated and desilylated to 3,7-diacetate. Subsequent oxidation with pyridine-chromium trioxide complex gave 19-aldehyde, which was transformed into the corresponding protected 19-( O-carboxymethyl)oxime. Successive ketal cleavage, deacetylation, and methyl ester splitting gave the final (19E)-3β,7α-dihydroxy-17-oxoandrost-5-en-19-al 19-( O-carboxymethyl)oxime, designed as a hapten for 7α-hydroxydehydroepiandrosterone immunoassays.