Synthesis and characterization by1H and13C nuclear magnetic resonance spectroscopy of 17α-hexanoic derivatives of 5α-dihydrotestosterone and testosterone

Article abstract of DOI:10.1016/0039-128X(92)90070-P

The synthesis and characterisation of 17α-(6′-hexanoic acid) derivatives of 5α-dihydrotestosterone and testosterone, useful as ligands for affinity chromatography purification or as precursors for affinitylabeling of androgen-binding proteins, is described. Alkynylation of 3-ethylenedioxy-, 3β-hydroxy-, and 3β,5-dihydroxy-5α-androstan-17-one precursors with the potassium derivative of 5-hexyn-1-ol led to the corresponding 17α-(6′-hydroxyhex-1′-ynyl) derivatives, which were hydrogenated over 10% Pt-C catalyst to give 17α-(6′-hydroxyhexyl) derivatives. Chromic acid oxidation of the primary hydroxy group of the 3-ethylenedioxy-17-hexyl intermediate into carboxylic acid followed by acid cleavage of the 3-ketal group gave 17α-(5′-carboxypentyl)-5α-dihydrotestosterone, which was also obtained directly by chromic acid oxidation of the 3β-hydroxy intermediate. Chromic acid oxidation of the primary hydroxy group of the 3β,5α-dihydroxy precursor resulted in a 5α-hydroxy-3-oxo intermediate, which was dehydrated to give 17α-(5′-carboxypentyl)testosterone. The 17α configuration of these derivatives and of synthetic precursors was established by comparing their molecular rotations and their ¹H and ¹³C nuclear magnetic resonance (NMR) spectra including solvent effects, with data reported for 17α- or 17β-substituted steroid analogs as well as with ¹H and ¹³C NMR reference data recorded in this work for 17α-ethynyltesfosterone, 17α-ethynyl-19-nortestosterone, 17α-ethyl-19-nortestosterone, 17αmethyltestosterone, and 17α-methyl-5α-dihydrotestosterone.