Combining Laccase-Mediated Dimerization of Resveratrol and Centrifugal Partition Chromatography: Optimization of E-Labruscol Production and Identification of New Resveratrol Dimers

Resveratroldimers are of great interest for pharmaceutical andcosmetic applications. Nevertheless, the yield of their bioproductionis limited by both the competition between the possible radical-radicalcoupling pathways and complex isolation procedures. Alternative organicsynthesis methods do not afford higher yields. Although enzymaticroutes can provide dimers in one step from resveratrol, biocatalysisoptimization is required to improve yields and orient radical-radicalcoupling selectivity toward a specific resveratrol dimer, E-labruscol herein. After a rapid study of the relativeimportance of the biocatalysis parameters, a design of experimentswas implemented to produce E-labruscol in high yieldby laccase-mediated dimerization of resveratrol. E-labruscol and & delta;-viniferin were identified and isolated byflash chromatography as major products in 21 and 52% yields, respectively.As an alternative to purification on silica gel, efficient separationof the aforementioned compounds was achieved by centrifugal partitionchromatography (CPC). This technology provided & delta;-viniferin in63.1% yield (90% purity) and labruscol isomers in 20.4% yield witha purity of 95% after a CPC polishing step, but it also revealed thepresence of E-labruscol diastereomers, leachianolF and leachianol G, as major reaction products, as well as less abundantproducts: pallidol, Z-labruscol, & epsilon;-viniferin,and two new resveratrol dimers named iso-& delta;-viniferin and iso-& epsilon;-viniferin. Challenging synthesis and purificationof the valuable dimerof resveratrol E-labruscol were optimized. Additionally,four new resveratrol dimers were identified.