Chemical synthesis of 24-β-d-galactopyranosides of bile acids: a new type of bile acid conjugates in human urine

A method is reported for the preparation of the C-24 carboxyl-linked β-d-galactopyranosides of lithocholic, deoxycholic, chenodeoxycholic, ursodeoxycholic, and cholic acids, two of which were recently identified as a novel type of the metabolites of bile acids excreted in human urine. Direct esterification (galactosidation) of the unprotected bile acids with 2,3,4,6-tetra-O-benzyl-d-galactopyranose in the presence of 2-chloro-1,3,5-trinitrobenzene as a coupling agent and subsequent hydrogenolysis of the resulting benzyloxy-protected bile acid 24-β-d-galactopyranosides over 10% palladium on charcoal under atmospheric pressure afforded the title compounds. The structures of the bile acid acyl galactosides were confirmed by measuring several 1H-1H and 1H-13C shift correlated 2D NMR.