Total Synthesis of Resveratrol and Stilbenes

Plants face many challenges during their life cycle, including injury, drought, heat, salt, UV light, cold, and attacks by various animals and phytopathogenic microbes. Thus, it has developed a complex defense system with inherent and active resistance mechanisms to withstand these pressures. Phytoalexins, which are low-molecular-weight secondary metabolite products with biocidal activity that plants create in response to stress, have been the focus of many investigations. Since the idea of phytoalexins, resveratrol is a naturally occurring polyphenolic, non-flavonoid substance that is a member of the stilbenoids, a group of molecules representative of various biological activities and widely recognized for its several health advantages, including its ability to prevent cancer and heart disease. Resveratrol may be found in a variety of plants, including berries, nuts, and grapes. The biosynthesis of stilbenes begins with the phenylpropanoid pathway, where phenylalanine is converted to cinnamic acid, followed by p-coumaric acid and pcoumaroyl-CoA. In the synthesis of resveratrol, stilbene synthase (STS) plays a crucial role which catalyzes the condensation of three molecules of malonyl-CoA synthesized from Acetyl-CoA and one molecule of coumaroyl-CoA to form the Stilbene backbone. Primary Resveratrol derivatives are produced by hydroxylation, glycosylation, O-methylation, and prenylation methods and also exhibit anti-inflammatory, anti-rheumatoid, and anti-neurodegenerative properties. For commercial use, resveratrol is isolated from Polygonum cuspidatum plants, and it is difficult to extract sufficient amounts of resveratrol as these plants produce it in response to stress management. Hence, there is a great need for highly effective synthetic methods for the large-scale preparation of these stilbenes. Currently, a number of synthetic approaches for resveratrol and its analogs have been developed through Heck, Wittig, Horner, and Emmons-Wadsworth reactions; the formation of a carbon-carbon double bond in trans-configuration is a crucial step in the synthetic reaction. While obtaining resveratrol and its derivatives, as well as oligomeric forms, in sufficient quantities to evaluate their activity through plant sourcing or total synthesis can be challenging, biocatalytic, enzymatic, and green chemistry methods may offer a competitive means of producing biologically active stilbenes on a large scale and at a low cost.