Rh-Catalyzed C–H alkylation enabling modular synthesis of CF3-substituted benzannulated macrocyclic inhibitors of B cell responses

Abstract

Inspired by aspirin and chalcone, herein, we describe a modular biomimetic strategy to achieve a new class of CF₃-bearing benzannulated macrolactams. The key to the success of macrolactams was the utilization of a highly chemoselective Rh(III)-catalyzed native carboxylic acid-directed C–H alkylation. Moreover, the unique CF₃-containing benzannulated macrocycles showed decent immunosuppressive effects on B cells in vitro, including proliferation, activation, and antibody production upon specific stimulation implicating TLR and BCR signaling.