Potential bile acid metabolites. 24. An efficient synthesis of carboxyl-linked glucosides and their chemical properties

A facile and efficient synthesis of the carboxyl-linked glucosides of bile acids is described. Direct esterification of unprotected bile acids with 2,3,4,6-tetra-O-benzyl-D-glucopyranose in pyridine in the presence of 2-chloro-1,3,5-trinitrobenzene as a coupling agent afforded a mixture of the α- and β-anomers (ca. 1:3) of the 1-O-acyl-D-glucoside benzyl ethers of bile acids, which was separated effectively on a C₁₈ reversed-phase chromatography column (isolated yields of α- and β-anomers are 4-9% and 12-19%, respectively). Subsequent hydrogenolysis of the α- and β-acyl glucoside benzyl ethers on a 10% Pd-C catalyst in acetic acid/methanol/EtOAc (1:2:2, by vol) at 35°C under atmospheric pressure gave the corresponding free esters in good yields (79-89%). Chemical specificities such as facile hydrolysis and transesterification of the acyl glucosides in various solvents were also discussed.