Synthesis of Cortol 3-Glucuronides and Cortolone 3-Glucuronides

The synthesis of the 3-glucuronides of 20α-cortolone and their 20β-epimers is described. The cortol 20, 21-diacetates (3, 10) and cortolone 20, 21-diacetates (6, 12) were the key intermediates. Sodium borohydride reduction of the carbonyl group at C-20 in 21-acetoxy-3α, 11β, 17α-trihydroxy-5β-pregnan-20-one 3-tert-butyldimethylsilyl ether (1) or its 11-oxo derivative (4) followed by acetylation of the product with acetic anhydride gave the silyl ether-acetates (2, 5), which, on removal of the protecting group at C-3 with sulfuric acid, were converted into the desired 20β-intermediates (3, 6). On the other hand, the 20α-acetates, 10 and 12, were synthesized from methyl 20α-acetoxy-3α-tert-butyldimethylsilyloxy-17α-hydroxy-11-oxo-5β-pregnan-21-oate (7). Introduction of the glucuronyl residue at the C-3 position was carried out by means of the Koenigs-Knorr reaction.