A novel synthesis of tetrahydrocortisone 3-glucuronide

Abstract

A new route for the synthesis of tetrahydrocortisone 3-glucuronide has been developed with cortisone acetate as a starting material. The key step was using lithium tri-tert-butoxyaluminum hydride to reduce the C-3 carbonyl group of 5β-dihydrocortisone acetate (8) to provide 3α-5β-tetrahydrocortisone acetate (5). Then, Koenig–Knorr method was used for glycosylation with glycosyl bromide as the donor, cadmium carbonate as promoter and 4Å molecular sieves as dehydrating agent to give high yield of the desired product. The new route is shorter and gives higher yield than that reported in the literature.