A 13C NMR approach to categorizing potential limitations of α,β-unsaturated carbonyl systems in drug-like molecules

Compounds that contain an α,β-unsaturated carbonyl moiety are often flagged as potential Michael acceptors. All α,β-unsaturated carbonyl moieties are not equivalent, however, and we sought to better understand this system and its potential implications in drug-like molecules. Measurement of the 13C NMR shift of the β-carbon and correlation to in vitro results allowed compounds in our collection to be categorized as potential Michael acceptors, potential substrates for NADPH, or as photoisomerizable. Compounds that contain an α,β-unsaturated carbonyl moiety are often flagged as potential Michael acceptors. All α,β-unsaturated carbonyl moieties are not equivalent, however, and we sought to better understand this system and its potential implications in drug-like molecules. Measurement of the 13C NMR shift of the β-carbon and correlation to in vitro results allowed compounds in our collection to be categorized as potential Michael acceptors, potential substrates for NADPH, or as photoisomerizable.