Premium
Structure–property relationship study of the HPLC enantioselective retention of neuroprotective 7‐[(1‐alkylpiperidin‐3‐yl)methoxy]coumarin derivatives on an amylose‐based chiral stationary phase
Author(s) -
Pisani Leonardo,
Rullo Mariagrazia,
Catto Marco,
Candia Modesto,
Carrieri Antonio,
Cellamare Saverio,
Altomare Cosimo Damiano
Publication year - 2018
Publication title -
journal of separation science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.72
H-Index - 102
eISSN - 1615-9314
pISSN - 1615-9306
DOI - 10.1002/jssc.201701442
Subject(s) - chemistry , substituent , enantiomer , enantioselective synthesis , hydrogen bond , chiral column chromatography , acceptor , chiral resolution , chiral derivatizing agent , chirality (physics) , combinatorial chemistry , stereochemistry , organic chemistry , molecule , physics , condensed matter physics , catalysis , nambu–jona lasinio model , chiral symmetry breaking , quantum mechanics , quark
The enantiomer separation of a number of racemic 7‐[(1‐alkylpiperidin‐3‐yl)methoxy]coumarin derivatives, some of which show outstanding in vitro multitarget neuroprotective activities, was successfully achieved on a polysaccharide‐based chiral stationary phase, bearing amylose tris(3,5‐dimethylphenylcarbamate) as a chiral selector, in normal polar mode (methanol and acetonitrile as the mobile phases). The majority of the screened selectands, especially those bearing 1‐(3‐X‐benzyl)piperidin‐3‐yl moieties, showed baseline enantiomer separations, and compound 8 (X = NO 2 ) was the best resolved ( α = 2.01; R S = 4.27). Linear free energy relationships, usefully complemented by molecular docking calculations, have the key role in enantioselective retention of aromatic interactions between π‐donor moieties in the chiral selector and π‐acceptor moieties in selectand, strengthened by hydrogen bond interaction between a hydrogen bond donor in the chiral selector and the hydrogen bond acceptor group(s) in the selectand. Statistically, reliable equations highlighted the importance of the substituent's size and substitution pattern ( meta better than para ) to affect the enantiorecognition of the title compounds. The chromatographic data support the scalability of the optimized experimental conditions for preparative purposes.