C-N Atropisomerism and Anti-MRSA Activity in 3-(2-Hydroxyphenyl)quinazolin-4-one Derivatives

Both atropisomers of 3-(2-hydroxyphenyl)quinazolin-4-one derivatives were prepared through optical resolution based on the formation of diastereomers with (S)-lactoyl chiral pool. Their rotational stabilities in solution depended to a considerable extent on which solvent was used. In alcohol and DMSO solvents, higher rotational stability was observed. This fact can be attributed to relatively strong solvation through an intermolecular hydrogen bond over an intramolecular hydrogen bond between the hydroxy hydrogen and the carbonyl oxygen. Furthermore, it was revealed that the anti-MRSA activity of the (P)-atropisomer is 16-fold more potent than that of the (M)-atropisomer.