Asymmetric synthesis of chiral (thio)chromanes and exploration on their structure–activity relationship in macrophages

Abstract

A CuCl/(R,R)-Ph-BPE-catalyzed enantioselective hydroallylation of 2H-chromenes and 2H-thiochromenes with allylic phosphate electrophiles is developed, which enables highly efficient and atom-economical asymmetric access to a series of 4-allyl chromanes and thiochromanes in high yields (up to 91%) with excellent enantioselectivities (up to 99% ee). These valuable chiral chromane and thiochromane products can serve as crucial intermediates for accessing bioactive compounds containing oxygen and sulfur atoms. In addition, the antioxidant and anti-inflammatory effects of various chromanes and thiochromanes were investigated in RAW 264.7 macrophages. The chromanes and thiochromanes exhibited significant inhibitory effects on the production of reactive oxygen species (ROS) and the secretion of pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). These findings indicate that the newly synthesized chromanes and thiochromanes hold promise as potential lead compounds for the development of antioxidant and anti-inflammatory drugs.