Chemical conversion of corticosteroids to 3 alpha,5 alpha-tetrahydro derivatives. Synthesis of allotetrahydrocortisol glucuronides and allotetrahydrocortisone glucuronides.
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.
Hosoda
H
H
Pharmaceutical Institute, Tohoku University, Sendai, Japan.
Osanai
K
K
Fukasawa
I
I
Nambara
T
T
D000305:Adrenal Cortex Hormones / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D008401:Gas Chromatography-Mass Spectrometry; D005965:Glucuronates / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D013760:Tetrahydrocortisol / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D013761:Tetrahydrocortisone / Q000031:analogs & derivatives* / Q000138:chemical synthesis
D000305:Adrenal Cortex Hormones; D005965:Glucuronates; D013761:Tetrahydrocortisone; D013760:Tetrahydrocortisol