Enzymatic Synthesis of α‐Glucosides of Resveratrol with Surfactant Activity

Abstract

Abstract:We report the synthesis of a series of aglucosyl derivatives of resveratrol (3,5,4'-trihydroxy-A C H T U N G T R E N N U N G stilbene) by a transglycosylation reaction catalyzed by the enzyme cyclodextrin glucanotransferase (CGTase) using starch as glucosyl donor. Several reaction parameters (temperature, solvent composition, enzyme concentration and starch/resveratrol ratio) were optimized. The yield of a-glucosylated products reached 50% in 24 h. The structures of the derivatives were determined by a combination of amyloglucosidase-hydrolysis tests, MS and 2D-NMR. Three families of products were obtained: glucosylated at 3-OH, at 4'-OH and at both 3-OH and 4'-OH. The bonds between glucoses were basically aA C H T U N G T R E N N U N G (1!4). Interestingly, the water solubilities of the a-glucosylated derivatives were at least 65-and 5-fold higher than those of resveratrol and the natural b-glucosylated derivative (piceid), respectively. In contrast with piceid, the synthesized a-glucosylated compounds exhibited surfactant activity, with critical micelle concentration (CMC) values in the range 0.5-3.6 mM. Although the incorporation of a glucosyl moiety caused a loss of antioxidant activity (more pronounced in the position 3-OH compared with 4'-OH), the fact that the glycosides need to be converted into the aglycones before they are absorbed minimizes such an effect. In contrast, the modification of physicochemical properties such as solubility and partition coefficient by glycosylation could exert a positive influence on the bioavailability of resveratrol.

Acceptor-induced modification of regioselectivity in CGTase-catalyzed glycosylations of p-nitrophenyl-glucopyranosides

“…With the corresponding a-anomer, p-nitrophenyl-a-glucopyranoside as acceptor, the formation of a(1?4)-glycosidic linkages was exclusively observed, indicating the importance of the anomeric configuration of the aglycon in position C-1. These results contribute to the understanding of side products formation observed previously by other groups 9,21 and indicate the importance of analyzing whole progress curves rather than conversions after short incubation times. In fact, the promiscuous selectivity of CGTases observed here as a side activity, can actually be used in the regioselective glycosylation synthesis at three different positions of the glucosyl moiety of the acceptor, as demonstrated here.…”

“…The coupling activity (i.e., the opening of cyclodextrin rings with subsequent transfer to acceptor molecules) and the disproportionation activity (transfer of linear malto-oligosaccharides to suitable acceptors) of CGTases represent a valuable tool for the intermolecular glycosylation of acceptor molecules. Among them, sugars 3,4 and glycosides [4][5][6] have been successfully glucosylated, but also non sugar-acceptors such as sugar alcohols, 7 polyols, 8 polyphenols, 9 flavonoides, 10 saponins, 11 or vitamins. 12 The hydrolytic activity (H 2 O as acceptor) of CGTases has been reported to be negligible for most CGTases.…”

Using Evaporation-Induced Self-Assembly for the Direct Drug Templating of Therapeutic Vectors with High Loading Fractions, Tunable Drug Release, and Controlled Degradation

“…A mix of (3-OH)-α-glucosylated resveratrol and (4'-OH)-α-glucosylated resveratrol was synthesized by scaling-up the enzymatic reaction described in reference (Torres 2011). Thin films were made by sol-gel process.…”

Resveratrol Functionalized Carboxymethyl-β-Cyclodextrin: Synthesis, Characterization, and Photostability

“…Recently, Marié's group demonstrated the authentically successful O-glycosylation of trans-resveratrol to overcome its low water solubility and stability by enzymatic synthesis of resveratrol α-glycosides from β-cyclodextrin-resveratrol complex in water [19]. Torres's group reported the synthesis of a series of α-glucosyl derivatives of resveratrol by a trans-glycosylation reaction catalyzed by the enzyme cyclodextrin glucanotransferase (CGTase) using starch as glucosyl donor [20].…”