A Scalable Biomimetic Synthesis of Resveratrol Dimers and Systematic Evaluation of their Antioxidant Activities

• Published in: Angewandte Chemie International Edition 2015-03, Vol.54 (12), p.3754-3757
• Main Authors: Matsuura, Bryan S., Keylor, Mitchell H., Li, Bo, Lin, YuXuan, Allison, Shelby, Pratt, Derek A., Stephenson, Corey R. J.
• Format: Article
• Language: English
• Subjects: Antioxidants; Antioxidants - chemical synthesis; Antioxidants - chemistry; Antioxidants - metabolism; Biological; Biological Products - chemical synthesis; Biological Products - chemistry; biomimetic synthesis; Biomimetics; Cell Line; Dimerization; Dimers; Humans; Indolequinones - chemistry; Oligomers; Oxidation-Reduction; Polycyclic Compounds - chemical synthesis; Polycyclic Compounds - chemistry; Polycyclic Compounds - metabolism; Precursors; quinone methides; Quinones; Radicals; resveratrol; Stereoisomerism; Stilbenes - chemical synthesis; Stilbenes - chemistry; Stilbenes - metabolism; Synthesis; total synthesis
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201409773

An efficient synthetic route to the resveratrol oligomers quadrangularin A and pallidol is reported. It features a scalable biomimetic oxidative dimerization that proceeds in excellent yield and with complete regioselectivity. A systematic evaluation of the natural products and their synthetic precursors as radical‐trapping antioxidants has revealed that, contrary to popular belief, this mode of action is unlikely to account for their observed biological activity. Persistence pays off: A concise synthesis of the resveratrol oligomers quadrangularin A and pallidol was achieved by leveraging the persistence of 2,6‐di‐tert‐butyl phenol derived radical and quinone methide intermediates. Evaluation of these compounds as radical‐trapping antioxidants is presented and the results demonstrate that this mode of action is unlikely to account for the observed biological activity.