Cyclic peptides represent a privileged class of scaffolds in drug discovery owing to their unique balance between structural rigidity and functional diversity. Herein, we disclose an indium(III)-catalyzed intramolecular dithiane-alkyne metathesis (DAM) that facilitates the efficient construction of Trp(C2)-alkene-cross-linked cyclic peptides with exclusive E-selectivity. This protocol directly transforms linear peptide precursors into diverse macrocycles with broad substrate scope, high atom economy, and operational simplicity. These features establish DAM as a mechanistically distinct and practical peptide stapling strategy.
Li et al. (Tue,) studied this question.