title: 15 beta-hydroxysteroids (Part IV). Steroids of the human perinatal period: the synthesis of 3 alpha,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one and its A/B-ring configurational isomers.
abstract: In recent years several 15 beta-hydroxysteroids have emerged pathognomonic of adrenal disorders in human neonates of which 3 alpha,15 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one (2) was the first to be identified in the urine of newborn infants affected with congenital adrenal hyperplasia. In this investigation we report the synthesis of the three remaining 3 xi,5 xi-isomers, namely 3 alpha,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one (3), 3 beta,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one (7) and 3 beta,15 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one (8) for their definitive identification in pathological conditions in human neonates. 3 beta,15 beta-Diacetoxy-17 alpha-hydroxy-5-pregnen-20-one (11), a product of chemical synthesis was converted to the isomeric 3 and 7, while conversion of 15 beta,17 alpha-dihydroxy-4-pregnen-3,20-dione (4), a product of microbiological transformation, resulted in the preparation of 8. In brief, selective acetate hydrolysis of 11 gave 15 beta-acetoxy-3 beta,17 alpha-dihydroxy-5-pregnen-20-one (12) which on catalytic hydrogenation gave 15 beta-acetoxy-3 beta,17 alpha-dihydroxy-5 alpha-pregnan-20-one (13) a common intermediate for the synthesis of the 3 beta(and alpha),5 alpha-isomers. Hydrolysis of the 15 beta-acetate gave 7, whereas oxidation with pyridinium chlorochromate gave 15 beta-acetoxy-17 alpha-hydroxy-5 alpha-pregnan-3,20-dione (14) which on reduction with L-Selectride and hydrolysis of the 15 beta-acetate gave 3. Finally, hydrogenation of 4 gave 15 beta, 17 alpha-dihydroxy-5 beta-pregnan-3,20-dione (10) which on reduction with L-Selectride gave 8.
authors.affiliation: Department of Metabolic Mass Spectrometry, Royal Prince Alfred Hospital, Camperdown, NSW, Sydney, Australia.
authors.forename: A Y
authors.initials: AY
authors.lastname: Reeder
authors.forename: G E
authors.initials: GE
authors.lastname: Joannou
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006914:Hydroxysteroids / Q000138:chemical synthesis*; D007231:Infant, Newborn; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011279:Pregnanetriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D006914:Hydroxysteroids; D011279:Pregnanetriol; C032093:3,15,17-trihydroxypregnan-20-one