Theoretical studies about the influence of different ring substituents on the nucleophilic ring opening of three-membered heterocycles and possible implications for the mechanisms of cysteine protease inhibitors

Epoxides, aziridines, and thiiranes are electrophilic building blocks that are widely used in synthetic organic chemistry and also as electrophilic 'warheads' for irreversible peptidic or peptidomimetic cysteine protease inhibitors. The experimental results concerning variations in the reactivities and the regioselectivities and also the different reasons for the increased inhibition potency of three-membered heterocycles containing an acidic substituent are discussed