Asymmetric synthesis of flavanols via Cu-catalyzed kinetic resolution of chromenes and their anti-inflammatory activity.

Abstract

Flavanols are privileged heterocyclic compounds in medicinal chemistry. It is notable to develop an efficient and straightforward protocol for accessing chiral flavanols with precise control of the stereocenters. Here, a highly efficient kinetic resolution of chromenes was reported via Cu-catalyzed asymmetric hydroboration. This previously unidentified approach features a one-step synthesis of chiral flavan-3-ols containing two vicinal stereogenic centers via a highly efficient kinetic resolution (s factor up to 1060, >99% ee for most products). In addition, the anti-inflammation effects of these diversified flavan-3-ols were studied by the in vitro experiments and RNA sequencing analysis. These flavan-3-ols showed inhibitory effects on the secretion of pro-inflammation cytokines including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor–α (TNF-α), as well as inhibiting the inflammation responses through down-regulating the gene transcriptions closely related to PI3K-Akt signaling pathway and TNF signaling pathway. The results suggested that these newly synthesized flavan-3-ols have the potential to be lead compounds for anti-inflammatory drugs.