Optimization and Green Metrics Analysis of the AgOAc-Mediated Dimerization of Piceid: Toward a High-Yielding and More Sustainable Access to δ-Viniferin and Synthesis of New Piceid Dimers

Abstract

Stilbenes are particularly studied for their biological properties. Among them, resveratrol and piceid, present in relatively large quantities in Nature, have already demonstrated interesting characteristics. Dimers and oligomers of resveratrol are also very promising, especially, δ-viniferin for which an elegant synthetic method based on the hydrolysis of piceid dimer has been reported. Nevertheless, while the hydrolysis is quantitative, to date, the synthesis of the piceid dimer has only been described in presence of laccase in toxic methanol and with a relatively average yield (46%). With a view to offering a greener and higher yielding dimerization of piceid, this study aims at (1) conducting the dimerization in presence of AgOAc in ethanol, (2) determining the influence of reaction parameters and the optimal conditions by using a Design of Experiment (DoE), (3) assessing the EcoScale and Process Mass Index (PMI) of the new procedure, and (4) comparing it with the laccase-mediated procedure. Data demonstrated that the AgOAc-mediated dimerization of piceid proceeds in higher yield (ca. 64% vs 46%), with a better EcoScale (68 vs 32), while being more economical (PMI score = 2.5 vs 71.4) and using a green solvent (EtOH).Moreover, through this novel route, we were able to identify and fully characterize new dimers that were not reported in the literature so far.