A rhodium-catalyzed [4 + 2] annulation strategy to synthesize pyranone-mounted tyrosines with anti-neuroinflammatory activity

Abstract

Rh(III)-catalyzed [4 + 2] annulation of C3_Ar-formyl tyrosine ester with internal alkynes furnished di-substituted pyranone-mounted tyrosine-based unnatural amino acids in high yields. Selected compounds exhibited intrinsic viscosity-responsive fluorescence and favorable biocompatibility in microglial and neuroblastoma cells. Of these, one of the products showed efficient cellular uptake, preserved mitochondrial health, reduced ROS levels, and suppressed nitrite production in LPS-activated microglia, underscoring its potential as a bioactive fluorescent probe for modulating neuroinflammatory responses.