Axial chirality in biaryl N,N‐dialkylaminopyridine derivatives bearing an internal carboxy group

Abstract

Axial chirality in N,N-dimethylaminopyridines as well as N,Ndipropylaminopyridines bearing an internal carboxy group were evaluated based on their racemization barriers and circular dichroism spectra. The halflife of racemization of N,N-dipropylaminopyridine derivative 2 was estimated to be 19.7 days at 20 C. Its enantiomers isolated as optically active forms showed positive-negative and negative-positive Cotton effects for (+)-2 and (−)-2, respectively, from 310 to 210 nm. Furthermore, (−)-2 was applied as a chiral nucleophilic catalyst and exhibited asymmetric induction in acylative kinetic resolution of 1-(1-naphthyl)ethane-1-ol. K E Y W O R D Saxial chirality, circular dichroism acylative kinetic resolution, DMAP derivative

A nonneglectable stereochemical factor in drug development: Atropisomerism

“…Studies on atropisomers in drug discovery date back to 1983 41 . With the increasing attention on atropisomerism, research on various aspects of the asymmetric synthesis, resolution, and biological evaluation of atropisomers is substantially increasing 4,30,42–50 . Herein, we focus on the biological activities and pharmacokinetic and toxicity properties of various atropisomers and highlight the role of atropisomerism in drug design.…”