Improved synthesis of 16alpha-hydroxylated androgens: intermediates of estriol formation in pregnancy.
16alpha-Hydroxyandrostenedione (16alpha-hydroxyandrost-4-ene-3,17-dione), 16alpha-hydroxytestosterone (16alpha,17beta-dihydroxyandrost-4-en-3-one) and 16alpha-hydroxydehydroepiandrosterone 3-sulfate (3beta, 16alpha-dihydroxyandrost-5-en-17-one 3-monosulfate) were synthesized by a new chemical approach with much improved yield. 16alpha-Bromoandrostendione was converted to the hydrazone of 16alpha-hydroxyandrostenedione which gave 16alpha-hydroxyandrostenedione on acid hydrolysis in total 63% yield. Oxidation of 16alpha-hydroxydehydroepiandrosterone with Jones' reagent also selectively afforded 16alpha-hydroxyandrostenedione. 16alpha-Hydroxytestosterone was observed by selective reduction of 16alpha-hydroxyandrostenedione with sodium borohydride. Reaction of 16alpha-hydroxydehydroepiandrosterone with chlorosulfonic acid in pyridine selectively gave the 3-monosulfate. The structure of the sulfate was deduced from its solvolysis to the starting material, and its acetylation and subsequent solvolysis to 16alpha-hydroxydehydroepiandrosterone 16-acetate. All procedures are suitable for large scale synthesis without the use of microorganisms.
D000728:Androgens / Q000138:chemical synthesis* / Q000378:metabolism; D000735:Androstenedione / Q000031:analogs & derivatives; D000818:Animals; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism; D004964:Estriol / Q000096:biosynthesis*; D005260:Female; D006915:Hydroxytestosterones / Q000138:chemical synthesis / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008722:Methods; D010084:Oxidation-Reduction; D011247:Pregnancy; D013055:Spectrophotometry, Infrared
D000728:Androgens; D006915:Hydroxytestosterones; D000735:Androstenedione; D003687:Dehydroepiandrosterone; C018202:16-hydroxyandrost-4-en-3,17-dione; D004964:Estriol