Flavan‐3‐ol C‐glycosides – Preparation and model experiments mimicking their human intestinal transit

Abstract

In order to study the human intestinal transit of flavan-3-ol C-glycosides, several C-glycosyl derivatives were prepared by non-enzymatic reaction of (+)-catechin with α-D-glucose, α-D-galactose and α-D-rhamnose, respectively. In contrast to literature data, we propose that the reaction mechanism proceeds in analogy to the rearrangement of flavan-3-ols during epimerization under alkaline conditions. Four of the 12 synthesized flavan-3-ol C-glycosides were incubated under aerobic conditions at 37°C using saliva (2 min) and simulated gastric juice (3 h). To simulate human intestine, the C-glycosides were also incubated under anaerobic conditions at 37°C both in human ileostomy fluid (10 h) and colostomy fluid (24 h), respectively. The flavan-3-ol C-glycosides under study, i.e. (+)-epicatechin 8-C-β-D-glucopyranoside (1a), (+)-epicatechin 6-C-β-D-glucopyranoside (1d), (+)-catechin 6-C-β-D-galactopyranoside (2b), (+)-catechin 6-C-β-D-rhamnopyranoside (3b) were analyzed in the incubation samples by HPLC-DAD and HPLC-DAD-MS/MS. They were found to be stable in the course of incubation in saliva, simulated gastric juice and ileostomy fluid and underwent degradation in colostomy fluid. While the 6-C-β-D-glucopyranoside 1d was completely metabolized between 2 and 4 h, decomposition of the 6-C-β-D-galactopyranoside 2b reached only 16 ± 2% within 4 h of incubation. Linear degradation rates of 1d and 2b in colostomy fluid differed significantly. As microbial metabolism of flavan-3-ols is known not to be influenced by the stereochemistry of the aglycon, varying degradation rates are ascribed to the effect of the sugar moiety. Based on these results we assume that flavan-3-ol C-glycosides pass through the upper gastrointestinal tract (oral cavity, stomach and small intestine) unmodified and are then metabolized by the colonic microflora.