Facile Synthesis of FimH Antagonist and Its Analogues: Simple Entry to Complex <i>C</i>-Mannoside Inhibitors of <i>E. coli</i> Adhesion

Synthesizing FimH antagonists is challenging because of their densely functionalized and stereochemically complex <i>C</i>-mannoside structures, resulting in low yields and lengthy processes. We present an efficient method for synthesizing <i>C</i>-mannoside FimH antagonists by nickel-catalyzed reductive coupling and stereocontrolled reduction, thereby significantly simplifying the process and enabling the synthesis of FimH antagonists in just four steps with an overall yield of 34-50%. This efficient synthesis holds significant potential for the rapid development of analogues targeting the treatment of urinary tract infections or Crohn's disease caused by <i>Escherichia coli</i> (<i>E. coli</i>).