An efficient synthesis of 5alpha-androst-1-ene-3,17-dione.
5alpha-Androst-1-ene-3,17-dione (5) as a prodrug of 1-testosterone (4) was prepared in four steps from 17beta-Acetoxy-5alpha-androstan-3-one (stanolone acetate) (1) in high yield. Thus, stanolone acetate (1) was brominated in the presence of hydrogen chloride in acetic acid to give 17beta-acetoxy-2-bromo-5alpha-androstan-3-one (2), which underwent dehydrobromination using lithium carbonate as base with lithium bromide as an additive to give 17beta-acetoxy-5alpha-androst-1-en-3-one (3) in almost quantitative yield with 97% of purity. Compound (3) was hydrolyzed with sodium hydroxide to give 17beta-hydroxy-5alpha-androst-1-en-3-one (4,1-testosterone), which was oxidized with chromium trioxide to afford 5alpha-androst-1-ene-3,17-dione (5). The overall yield of 5 was 78.2% with purity of 99%. In this method, the formation of 4-ene was diminished when 1-ene was introduced, and its mechanism was also discussed.
Zhang
Huyue
H
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 200032, China.
Qiu
Zhuibai
Z
D000735:Androstenedione / Q000138:chemical synthesis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013056:Spectrophotometry, Ultraviolet
D000735:Androstenedione; C003528:5-androstene-3,17-dione