Hydrazine hydrate facilitates efficient synthesis of cyclodipeptides for antibacterial screening.

We report a facile and efficient strategy for synthesizing cyclodipeptides through hydrazine hydrate-mediated cyclization of dipeptide esters under exceptionally mild conditions (room temperature, ethanol). This operationally simple protocol enables the gram-scale construction of 33 diverse cyclodipeptides from Boc-protected precursors in good yields (53-91%), without requiring heating, column chromatography, or incurring racemization. Notably, antibacterial screening revealed that four newly reported cyclodipeptides exhibit activity against E. coli, underscoring the utility of this method for generating bioactive molecules.