Synthesis and characterization by 1H and 13C nuclear magnetic resonance spectroscopy of 17 alpha-cyano, 17 alpha-aminomethyl, and 17 alpha-alkylamidomethyl derivatives of 5 alpha-dihydrotestosterone and testosterone.
17 alpha-Aminomethyl, 17 alpha-acetamidomethyl, and 17 alpha-hemiglutaramidomethyl derivatives of dihydrotestosterone and testosterone have been prepared by hydrocyanation of 3,3'-(ethylenedioxy)-5 alpha-androstan-17-one and 3,3'-ethylenedioxyandrost-5-en-17-one, reduction of the corresponding acetylated 17 alpha-cyanohydrins with lithium aluminium hydride, and acylation of the resulting 17 alpha-aminomethyl derivatives with either acetic anhydride or the mono acid chloride of glutaric acid mono methyl ester. Saponification of the 17 alpha-hemiglutaramidomethyl methyl esters gave the corresponding hemiglutaramido derivatives, while acid hydrolysis of the 3-ethylene ketal group of 17 alpha-acetamidomethyl and 17 alpha-hemiglutaramidomethyl derivatives regenerated the 3-oxo and 3-oxo-4-ene functions. The 17 alpha-configuration of 17-substituted steroids was determined by 1H and 13C NMR and confirmed by comparing with NMR data for 17 alpha- and 17 beta-cyano-17-hydroxyandrost-4-en-3-one, 17 beta-cyano-3,3'-(ethylenedioxy)androst-5-en-17-ol, 17 alpha-alkynyl, and 17 alpha-hexanoic derivatives of dihydrotestosterone and testosterone, of known 17-configurations. Several ambiguous assignments of 13C NMR signals of 17 alpha-substituted steroids and unsubstituted 17 beta-hydroxy or 17-oxo precursors have been resolved using steroid analogs deuterated at positions C5-7, or C16 for androstane derivatives, and at positions C6-7, or C7 for androstene derivatives. 17 alpha-Aminomethyl and 17 alpha-alkylamidomethyl derivatives of dihydrotestosterone and testosterone are useful intermediates for the access to potential ligands of androgen-binding proteins necessary for affinity chromatography purification or affinity-labeling experiments.
Mappus
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Institut National de la Santé et de la Recherche Médicale U 329, Pathologie Hormonale et Moléculaire, Hôpital Debrousse, Lyon, France.
Chambon
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C
Rolland de Ravel
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Grenot
C
C
Cuilleron
C Y
CY
D000081:Acetamides / Q000737:chemistry; D000107:Acetylation; D000215:Acylation; D000345:Affinity Labels; D000588:Amines / Q000737:chemistry; D000727:Androgen-Binding Protein / Q000378:metabolism; D002846:Chromatography, Affinity; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000737:chemistry*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D008968:Molecular Conformation; D015394:Molecular Structure; D011190:Potassium Cyanide; D012738:Sex Hormone-Binding Globulin / Q000302:isolation & purification; D013739:Testosterone / Q000031:analogs & derivatives* / Q000737:chemistry*
D000081:Acetamides; D000345:Affinity Labels; D000588:Amines; D000727:Androgen-Binding Protein; D007202:Indicators and Reagents; D012738:Sex Hormone-Binding Globulin; D013196:Dihydrotestosterone; D013739:Testosterone; C030686:acetamide; D011190:Potassium Cyanide