Rational Tuning of the Reactivity of Three-Membered Heterocycle Ring Openings via S_N 2 Reactions.

ABSTRACT: The development of small-molecule covalent inhibitors and probes continuously pushes the rapidly evolving field of chemical biology forward. A key element in these molecular tool compounds is the "electrophilic trap" that allows a covalent linkage with the target enzyme. The reactivity of this entity needs to be well balanced to effectively trap the desired enzyme, while not being attacked by off-target nucleophiles. Here we investigate the intrinsic reactivity of substrates containing a class of widely used electrophilic traps, the three-membered heterocycles with a nitrogen (aziridine), phosphorus (phosphirane), oxygen (epoxide) or sulfur atom (thiirane) as heteroatom. Using quantum chemical approaches, we studied the conformational flexibility and nucleophilic ring opening of a series o

SUBMITTER: Hansen T 

PROVIDER: S-EPMC9804865 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature