title: 15 beta-hydroxysteroids (Part III). Steroids of the human perinatal period: the synthesis of 3 beta, 15 beta, 17 alpha-trihydroxy-5-pregnen-20-one. Application of n-butyl boronic acid protection of a 17,20-glycol.
abstract: We report the synthesis of 3 beta,15 beta,17 alpha-trihydroxy-5-pregnen-20- one (1) from 3 beta,15 beta-dihydroxy-5,16-pregnadien-20-one (11) in 7 steps using boronate derivatives as a means of protecting the 17,20-glycol side-chain of steroid intermediates. 16 alpha,17 alpha-Epoxy-3 beta,15 beta-dihydroxy-5- pregnen-20-one (12), an intermediate in the synthesis was prepared by epoxidation of 11 using a mixture of sodium hydroxide and hydrogen peroxide. Reduction of 12 with lithium aluminium hydride gave the two isomers of 5-pregnene-3 beta, 15 beta,17 alpha,20 (S+R)-tetrol (13a and 13b) which on subsequent reaction with n-butyl boronic acid gave 5-pregnene-3 beta,15 beta,17 alpha, 20(S+R)-tetrol 17 alpha,20-butyl boronate (15a and 15b). Acetylation with acetic anhydride and pyridine yielded 3 beta,15 beta-diacetoxy-5-pregnene-17 alpha,20(S+R)-diol 17 alpha,20(S+R)-butyl boronate (15c and 15d). Oxidative cleavage of the boronic ester using sodium hydroxide and hydrogen peroxide gave 3 beta,15 beta-diacetoxy-5-pregnene-17 alpha,20(S+R)-diol (13c and 13d). After isolation of these latter two products, dibromide protection of the C-5,6 olefin of 13d and oxidation with N-bromosuccinimide gave 3 beta,15 beta-diacetoxy-17 alpha-hydroxy-5-pregnen-20-one (16) which on deacetylation gave in good yield (35%) the desired product 3 beta,15 beta,17 alpha-trihydroxy-5-pregnen-20-one (1) in an overall yield of 24% from 11.
authors.affiliation: Department of Metabolic Mass Spectrometry, Royal Prince Alfred Hospital, Camperdown, New South Wales, Sydney, Australia.
authors.forename: G E
authors.initials: GE
authors.lastname: Joannou
authors.forename: A Y
authors.initials: AY
authors.lastname: Reeder
mesh_terms: D006907:17-alpha-Hydroxypregnenolone / Q000031:analogs & derivatives* / Q000378:metabolism; D001896:Boron Compounds / Q000737:chemistry*; D006018:Glycols / Q000737:chemistry*; D006801:Humans; D007231:Infant, Newborn; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods
chemical_list: D001896:Boron Compounds; D006018:Glycols; D006907:17-alpha-Hydroxypregnenolone; C030433:n-butylboronic acid; C032092:3 beta,15 beta,17 alpha-trihydroxy-5-pregnen-20-one