Palladium(II)‐Catalyzed Site‐Selective C(sp³)−H Alkynylation of Oligopeptides: A Linchpin Approach for Oligopeptide–Drug Conjugation

The palladium(II)-catalyzed C(sp³ )-H alkynylation of oligopeptides was developed with tetrabutylammonium acetate as a key additive. Through molecular design, the acetylene motif served as a linchpin to introduce a broad range of carbonyl-containing pharmacophores onto oligopeptides, thus providing a chemical tool for the synthesis and modification of novel oligopeptide-pharmacophore conjugates by C-H functionalization. Dipeptide conjugates with coprostanol and estradiol were synthesized by this method for potential application in targeted drug delivery to tumor cells with overexpressed nuclear hormone receptors.