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

Abstract

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 alpha- and beta-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 alpha- and beta-anomers are 4-9% and 12-19%, respectively). Subsequent hydrogenolysis of the alpha- and beta-acyl glucoside benzyl ethers on a 10% Pd-C catalyst in acetic acid/methanol/EtOAc (1:2:2, by vol) at 35 degrees 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.

1H and 13C NMR signal assignments of carboxyl‐linked glucosides of bile acids

“…As has been pointed out previously, 3,6 the free ester glycosides of bile acids undergo relatively rapid transesterification in a protic solvent such as methanol to give the corresponding methyl esters. In order to prevent such chemical transformation and/or decomposition of the substrates dissolved in CD 3 OD solvent, a series of all of the 1D and 2D NMR spectra were measured within a few days after the preparation of the sample solutions.…”

“…1) examined in this study have recently been synthesized in our laboratories. 6 The following trivial names and abbreviations are used in this paper:…”

“…6 This paper describes the complete 1 H and 13 C resonance assignments of the ester glucosides of bile acids and the results were compared with those of the analogous 3-ether glucosides of bile acids.…”

Direct capillary gas chromatographic analysis and thermal stability of bile acid esters of glucose

“…We have recently prepared a series of both the ct and fl anomers at C-24 of bile acid esters (1 14) of glucose as authentic reference standards, to examine their chemical, physicochemical, and biological properties and their chromatographic behavior [13]. We also revealed the chemical specificity of the bile acid esters, which are susceptible both to hydrolysis and to transesterification, particularly in protonic solvents such as methanol, to give, readily, the corresponding C-24 free acids and/or the methyl esters.…”

“…All the ~ and/? anomers of bile acid esters (1 14) and ethers (15 20) of glucose were from our collection, and were recently synthesized in these laboratories [13]. The silylating reagents, hexamethyldisilazane (HMDS) and trimethylchlorosilane (TMCS), were obtained from Tokyo Kasei Kogyo (Tokyo, Japan).…”