Paper
Chemical conversion of corticosteroids to 3 alpha,5 alpha-tetrahydro derivatives. Synthesis of allotetrahydrocortisol glucuronides and allotetrahydrocortisone glucuronides.
Published Jul 1, 1990 · H. Hosoda, K. Osanai, I. Fukasawa
Chemical & pharmaceutical bulletin
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Abstract
The synthesis of the 3- and 21-glucuronides of allotetrahydrocortisol (allo-THF) and allotetrahydrocortisone (allo-THE) is described. 5 alpha-Dihydrocortisol (5) was prepared by selective hydrogenation of 21-acetoxy-3, 11 beta, 17 alpha-trihydroxy-3,5-pregnadien-20-one 3-ethyl ether (3), followed by acid hydrolysis and saponification. When 5 alpha-dihydrocortisol 21-tetrahydropyranyl ether (6) was treated with potassium tri-sec-butylborohydride in tetrahydrofuran under mild conditions, regioselective and stereoselective reduction at C-3 took place to give allo-THF 21-tetrahydropyranyl either (7). This compound was converted into the 3- and 21-monoacetates of allo-THF and allo-THE, key intermediates. Introduction of the glucuronyl residue at C-3 or C-21 was carried out by means of the Koenigs-Knorr reaction. Prior to saponification yielding the 3-glucuronides (20,23), the alkali-sensitive ketol side chain at C-17 was protected as 20-semicarbazones.
This study presents a method for synthesis of 3- and 21-glucuronides of allotetrahydrocortisol and allotetrahydrocortisone, which can be used for the selective conversion of corticosteroids to their tetrahydro derivatives.
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