title: Chemical conversion of corticosteroids to 3 alpha,5 alpha-tetrahydro derivatives. Synthesis of 5 alpha-cortol 3-glucuronides and 5 alpha-cortolone 3-glucuronides.
abstract: The synthesis of the 3-glucuronides of 5 alpha-cortol-20 alpha, 5 alpha-cortolone-20 alpha and their 20 beta-epimers is described. The 5 alpha-cortol 20,21-diacetates (12, 17) and 5 alpha-cortolone 20,21-diacetates (14, 19) were the key intermediates. Sodium borohydride reduction of the carbonyl group at C-20 in 5 alpha-tetrahydrocortisol 3-tert-butyldimethylsilyl ether 17,21-acetonide (8) gave the 20 alpha-hydroxy-acetonide (9). Selective removal of the acetonide ring was successful when the 20 alpha-acetoxy-17 alpha,21-acetonide (10) was treated with 50% acetic acid. Subsequent acetylation with acetic anhydride in pyridine, followed by removal of the protecting group at C-3 in the silyl ether-acetate (11) gave the desired 20 alpha-intermediate (12). The 11-ketone (14) was prepared from 11 by oxidation with pyridinium chlorochromate, followed by desilylation. The 20 beta-acetates (17, 19) were synthesized from 21-acetoxy-3 alpha,11 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one 3-tert-butyldimethylsilyl ether (15). Introduction of the glucuronyl residue at C-3 was carried out by means of the Koenigs-Knorr reaction.
authors.affiliation: Pharmaceutical Institute, Tohoku University, Sendai, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hosoda
authors.forename: K
authors.initials: K
authors.lastname: Osanai
authors.forename: T
authors.initials: T
authors.lastname: Nambara
mesh_terms: D000305:Adrenal Cortex Hormones / Q000737:chemistry*; D005965:Glucuronates / Q000138:chemical synthesis; D011278:Pregnanes / Q000138:chemical synthesis*
chemical_list: D000305:Adrenal Cortex Hormones; D005965:Glucuronates; D011278:Pregnanes; C003545:cortolone; C003544:cortol