A concise synthesis of the 3-O-beta-D- and 4'-O-beta-D-glucuronide conjugates of trans-resveratrol.
trans-Resveratrol ((E)-3,4',5-trihydroxystilbene, 1) is a phytoalexin produced naturally in plants and grape skins as a stress metabolite protecting against fungal attack. Widespread interest in this apparently structurally simple molecule and synthetic stilbene analogues has arisen in recent years due to the discovery of its antioxidant, antiinflammatory, and anti-carcinogenic activities, among others. Although O-conjugation with glucuronic acid in vivo is known to represent a significant metabolic pathway for polyphenolic compounds in general and 1 in particular, preclinical studies have been hampered by the lack of chemically pure, completely characterized reference standards of both regioisomeric 3-O-beta-d- and 4'-O-beta-d-glucuronide conjugates of 1 for adequate identification and quantification of these significant metabolites. The present work describes a concise, convergent synthesis of both 3-O-beta-d- and 4'-O-beta-d-glucuronide conjugates of 1 using a strategy based on a novel Heck coupling of iodoaryl-O-beta-d-glucuronate esters with appropriately substituted styrenes, such that highly pure multimilligram to gram quantities of both the 3-O-beta-d- and 4'-O-beta-d-glucuronide conjugates of 1 can now be conveniently synthesized.
Learmonth
David A
DA
Laboratory of Chemistry, Department of Research & Development, BIAL, A Avenida da Siderurgia Nacional, 4745-457 S. Mamede do Coronado, Portugal. david.learmonth@bial.com
D020719:Glucuronides / Q000737:chemistry*; D006001:Glycoconjugates / Q000138:chemical synthesis*; D012015:Reference Standards; D000077185:Resveratrol; D013237:Stereoisomerism; D013267:Stilbenes / Q000737:chemistry*; D014920:Wine / Q000032:analysis / Q000592:standards
D020719:Glucuronides; D006001:Glycoconjugates; D013267:Stilbenes; D000077185:Resveratrol