Creating a Water-Soluble Resveratrol-Based Antioxidant by Site-Selective Enzymatic Glucosylation

The phytochemical resveratrol (trans‐3,5,4′‐trihydroxystilbene) has drawn great interest as health‐promoting food ingredient and potential therapeutic agent. However, resveratrol shows vanishingly low water solubility; this limits its uptake and complicates the development of effective therapeutic forms. Glycosylation should be useful to enhance resveratrol solubility, with the caveat that unselective attachment of sugars could destroy the molecule's antioxidant activity. UGT71A15 (a uridine 5′‐diphosphate α‐D‐glucose‐dependent glucosyltransferase from apple) was used to synthesize resveratrol 3,5‐β‐D‐diglucoside; this was about 1700‐fold more water‐soluble than the unglucosylated molecule (∼0.18 mM), yet retained most of the antioxidant activity. Resveratrol 3‐β‐D‐glucoside, which is the naturally abundant form of resveratrol, was a practical substrate for perfect site‐selective conversion into the target diglucoside in quantitative yield (g L−1 concentration). Site‐selective 5‐O‐β‐D‐glucosylation of the naturally abundant piceid by an UDP‐glucose‐dependent apple glucosyltransferase was used to prepare the highly water‐soluble resveratrol 3,5‐β‐D‐diglucoside in high yield. The diglucoside was shown to exhibit antioxidant activity similar to that of the unglucosylated resveratrol, which is barely soluble in water.