Synthesis and evaluation of pseudopeptide chiral stationary phases for enantioselective resolution

Poly(2-oxazoline)s are regarded as bioinspired polymers due to their structural relation to polypeptides. In this work, a new kind of poly(2-oxazoline)s containing dipeptide segments in the side chains was synthesized through a bottom-up protocol, which involves ring-opening copolymerization of 2-(N-Boc-l-2-pyrrolidinyl)-2-oxazoline (PyOX_Boc) with 2-(3-butenyl)-2-oxazoline (BuOX) followed by deprotection and amide coupling with N-protected L-proline. The resulting vinyl-functionalized polymers were subsequently immobilized onto mercaptopropylated silica bead matrices by means of thio-click chemistry and their potential as the chiral stationary phase (CSP) for high-performance liquid chromatography was preliminarily evaluated with a series of structurally different racemates. The results showed that this class of pseudopeptide CSPs is particularly adapted to the enantiomeric separation of 1,1'-bi-2-naphthol and acyloin compounds (such as benzoin) under normal-phase conditions. Moreover, an increase in the length of polymer main chains is beneficial to the enhancement of both enantioselectivity and resolution ability. The chiral discrimination of analytes by the polymeric selectors stems primarily from hydrogen bonding and π-π interactions as well as steric hindrance.