Synthesis of Cortoic Acid 3-Glucuronides

抄録

The synthesis of the 3-glucuronides of cortoic acids, metabolites of cortisol, is described. 20α-Cortolonic acid 3-glucuronide (11) and its 20β-epimer (12) were prepared starting from tetrahydrocortisone (1). The cortolonic acid 20-acetate methyl esters (7, 8) were the key intermediates. The 20-oxo-21-aldehyde (2) obtained from 1 by oxidation with cupric acetate was derivatized into 20-epimeric methyl cortolonates (3). When 3 was treated with tert-butyldimethylsilyl chloride and imidazole in dimethylformamide-pyridine, selective silylation of the hydroxyl group at C-3 took place. Subsequent acetylation with acetic anhydride in pyridine gave the separable 20-acetates (5, 6), which, on removal of the silyl group at C-3 with sulfuric acid, were converted into the desired intermediates. Introduction of the glucuronyl residue into the C-3 position was carried out by means of the Koenigs-Knorr reaction. The cortolic acid 3-glucuronides (21, 22) were synthesized from 5β-dihydrocortisol (13).