Glycosylated Stilbenes Biobased Production for Cosmetic Applications

Resveratrol and its derivatives, such as dimers, are of great interest for pharmaceutic and cosmetic applications. Nevertheless, bioproduction of dimers of resveratrol suffers from low yield – due to the competition of different radical-radical coupling patterns - and complex isolation procedures, whereas organic synthetic pathways remain long, fastidious without affording higher yield. Although enzymatic routes allow to synthesize dimers in one step from resveratrol, biocatalysis optimisation is required to improve yield and oriented radical-radical coupling selectivity toward a specific resveratrol dimer, E-Labruscol herein. Labruscol have demonstrated anticarcinogenic properties against two human skin malignant melanoma cancer cell lines. More investigations are required to decipher all its potential. Labruscol, was isolated from V. Labrusca L. cell suspensions culture. However, as 10 L of medium was required to recovered 41 mg of Labruscol, a new approach had to be considered to increase this yield. Although δ-viniferin was often reported as the major product present in the relatively complex mixture of oligomers obtained via the enzymatic dimerization of resveratrol, Ponzoni et al. have reported the presence of very small amount of E-Labruscol (≈5%) during laccase-mediated dimerization of resveratrol. Building on these findings, and having successfully achieved the quite challenging enzymatic synthesis of syringaresinol from sinapyl alcohol by reversing the initial selectivity of the enzyme for the β-O-4 dimer in a previous work, the aim of this study was to increase the yield of E-Labruscol by fine-tuning the biocatalysis conditions. After a rapid screening of conditions, the Design of Experiments (DoE) was implemented to access E-Labruscol through a laccase-mediated dimerization of resveratrol. Selected parameters – i.e., concentration in resveratrol, enzyme/substrate ratio, composition of the medium, addition rate of the enzymatic solution - were tested and included in the DoE to find the best conditions to yield E-Labruscol in large amounts. Two diastereomers of E-Labruscol, as well as δ-viniferin, were identified and isolated as major products (25% and 52% yields, respectively). Recovery of the target compounds from enzymatic solution was achieved through centrifugal partition chromatography (CPC), a technic that has already been proven efficient for the separation of grapevine cells culture and avoids the use of waste-generating silica gel chromatography. After CPC, fractions were submitted to 13C NMR dereplication workflow to identify compounds. When new structures were detected, preparative liquid chromatography was performed to isolate the targeted compounds. Then, structure elucidation of these compounds was achieved through NMR analysis (1D and 2D) and HRMS. This biocatalytic process was then successfully scaled-up (starting with 2 g of resveratrol) and provided 410 mg of E-Labruscol. This optimized laccase-mediated synthesis of E-Labruscol from resveratrol allows to, not only envisage subsequent (bio)chemical transformations of Labruscol to access novel compounds of interest, but also carry out biological activities assays. This dataset relates with the optimisation of an enzymatic-mediated oxidation of resveratrol toward Labruscol. It contains data about the activity of the enzyme, the design of experimented that has been performed and structural elucidation of new isolated dimers of resveratrol.