Complementary\nStrategies for Installation of Thioimidates\ninto Peptide Backbones

Thioimidates are a precursor and synthetic branch point\nto access\neither thioamide or amidine isosteres of the native amide (peptide\nbond). Previous syntheses of thioimidate-containing peptides were\nprone to side reactivity and required slow, cumbersome steps that\nwere difficult to monitor. We describe a more efficient approach to\ndirectly couple thioimidates onto the growing peptide chain. This\nwork also outlines optimal conditions for thioimidate formation on\nsolid support and identifies potential off-target sites for alkylation\nthat impact the choice of protecting group.