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

Org Biomol Chem. 2021 Apr 28;19(16):3589-3594. doi: 10.1039/d1ob00296a.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkylation
  • Animals
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / metabolism
  • Catalysis
  • Immunosuppressive Agents / chemical synthesis
  • Immunosuppressive Agents / chemistry
  • Immunosuppressive Agents / pharmacology*
  • Macrocyclic Compounds / chemical synthesis
  • Macrocyclic Compounds / chemistry
  • Macrocyclic Compounds / pharmacology*
  • Mice
  • Molecular Structure
  • Receptors, Antigen, B-Cell / metabolism
  • Rhodium / chemistry*
  • Signal Transduction
  • Toll-Like Receptors / metabolism

Substances

  • Immunosuppressive Agents
  • Macrocyclic Compounds
  • Receptors, Antigen, B-Cell
  • Toll-Like Receptors
  • Rhodium