Convenient syntheses of trans-resveratrol 3-O and 4′-O-β-d-glucuronides and a study of their aqueous stability

• Published in: Organic chemistry frontiers an international journal of organic chemistry 2024-05, Vol.11 (10), p.2720-2726
• Main Authors: Fraser, Megan K, Gorecka, Aleksandra, Yates, Edwin A, Iggo, Jonathan A, Baj, Krzysztof, Stachulski, Andrew V
• Format: Article
• Language: English
• Subjects: Acetates; Acetic acid; Aqueous solutions; Deacetylation; Isomerization; Phenolic compounds; Phenols; Piperazine; Reagents; Resveratrol; Stability; Stilbene
• ISSN: 2052-4110; 2052-4110
• DOI: 10.1039/d3qo01736b

The two isomeric monoglucuronides of the stilbene triol derivative, resveratrol, are thought to have potentially valuable biological activities, including possible antiproliferative properties, in common with resveratrol itself. In connection with a wider interest in naturally occurring phenolic glucuronides, we sought access to both of these conjugates from readily available resveratrol triesters. Selective monodeacylation using either chemical or enzymatic hydrolyses afforded the required diesters: subsequent glucuronidation using the trichloroacetimidate procedure, then mild hydrolysis, afforded the desired products. We also discovered a very mild, effective method for the anomeric deacetylation of the readily available methyl glucuronate β-tetraacetate using N-Me piperazine en route to the imidate. This reagent appears to have wider value in the deprotection of relatively activated acetates. We further studied the stability of the glucuronides in aqueous solution, and found remarkable differences in their properties, especially in the ready E/Z isomerisation of the 3-glucuronide.