Chemical Conversion of Corticosteriods to 3α, 5α-Tetrahydro Derivatives. Synthesis of 5α-Cortol 3-Glucuronides and 5α-Cortolone 3-Glucuronides

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The synthesis of the 3-glucuronides of 5α-cortol-20α, 5α-cortolone-20α and their 20β-epimers is described. The 5α-cortol 20, 21-diacetates (12, 17) and 5α-cortolone 20, 21-diacetates (14, 19) were the key intermediates. Sodium borohydride reduction of the carbonyl group at C-20 in 5α-tetrahydrocortisol 3-tert-butyldimethylsilyl ether 17, 21-acetonide (8) gate the 20α-hydroxy-acetonide (9). Selective removal of the acetonide ring was successful when the 20α-acetoxy-17α, 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 20α-intermediate (12). The 11-ketone (14) was prepared from 11 by oxidation with pyridinium chlorochromate, followed by desilylation. The 20β-acetates (17, 19) were synthesized from 21-acetoxy-3α-11β, 17α-trihydroxy-5α-pregnan-20-one 3-tert-butyldimethylsily ether (15). Introduction of the glucuronyl residue at C-3 was carried out by means of the Koenigs-Knorr reaction.