Synthesis and characterization by 1H and 13C nuclear magnetic resonance spectroscopy of 17α-hexanoic derivatives of 5α-dihydrotestosterone and testosterone

• Published in: Steroids Vol. 57; no. 3; pp. 122 - 134
• Main Authors: Mappus, Elisabeth, Renaud, Mélanie, de Ravel, Marc Rolland, Grenot, Catherine, Cuilleron, Claude Y.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.03.1992; Elsevier Science
• Subjects: 13C nuclear magnetic resonance; 17α-(5'-carboxypentyl)-5α-dihydrotestosterone; 17α-(5'-carboxypentyl)testosterone; 17α-alkynyl steroid derivatives; 1H nuclear magnetic resonance; Alicyclic compounds, terpenoids, prostaglandins, steroids; Caproates - chemical synthesis; Caproates - chemistry; Chemistry; Dihydrotestosterone - analogs & derivatives; Dihydrotestosterone - chemistry; Exact sciences and technology; Magnetic Resonance Spectroscopy; Molecular Conformation; Molecular Structure; Nandrolone - analogs & derivatives; Nandrolone - chemistry; nuclear magnetic resonance solvent effects; Organic chemistry; Preparations and properties; Steroids; Testosterone - analogs & derivatives; Testosterone - chemistry; 17α-(5'-carboxypentyl)-5α-dihydrotestosterone; 13C nuclear magnetic resonance; steroids; 17α-alkynyl steroid derivatives; nuclear magnetic resonance solvent effects; 1H nuclear magnetic resonance; 17α-(5'-carboxypentyl)testosterone; Steroid; Acetal; Aliphatic compound; Tertiary alcohol; Saturated compound; Ketone; Enone
• ISSN: 0039-128X; 1878-5867
• 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.