Chiral recognition of (18-crown-6)-tetracarboxylic acid as a chiral selector determined by NMR spectroscopy

The Development and Application of Chirotechnology Using Chiral Crown Ethers for Enantiomer Separation

“…11). 이외에도 NMR spectroscopy 분석기기를 이용하여 (+)-18-C-6-TA를 키랄선택자로 하여 PG와 alanine 그리고 그들의 ester 유도체 뿐만 아니라 thrombin inhibitor의 저해제의 키 랄 선구물질로 사용되는 diphenylalanine의 chiral solvating agent와 관련된 광학분리 연구가 보고되었다 [31][32][33]. H NMR spectra of Phe-ME and Phe-ME/18-C-6-TA complex with equimolar mixtures (20 mM each); (a) (L)-Phe-ME with 18-C-6-TA, (b) racemic Phe-ME with 18-C-6-TA, (c) racemic Phe-ME.…”

Noncovalent Interactions between ([18]Crown‐6)‐Tetracarboxylic Acid and Amino Acids: Electrospray‐Ionization Mass Spectrometry Investigation of the Chiral‐Recognition Processes

“…[9] In a search for the origin of the chiral recognition of a-amino acids in the presence of 18C6TA as a chiral selector, the interactions responsible for the differential affinities towards enantiomers were investigated for the specific case of phenylglycine by NMR spectroscopy and molecular dynamics calculations. [10] It was revealed that the polyether ring forms a bowl that is shaped by intramolecular hydrogen bonding involving the carboxylic groups located under the plane of the ring and situated on carbon atoms 3 and 12 of the polyether ring (Scheme 2). As a consequence, the upper face is open to allow intermolecular hydrogen bonding between the hydrogen atoms of the ammonium group and three oxygen atoms of the crown ether.…”

“…The key features for enantiomeric discrimination are 1) the three + NH···O hydrogen bonds in a tripod arrangement between polyether oxygen atoms and the ammonium moiety of the l or d enantiomer, 2) a hydrophobic interaction between the polyether ring of the host molecule and the phenyl moiety of the enantiomers, and 3) a hydrogen bond between the carboxylic acid of the crown ether and the carbonyl oxygen atom for the d enantiomer only. [10] This additional hydrogen bond is considered to be crucial for effective chiral discrimination because, as a consequence, the d isomer of phenylglycine would form a more favorable complex with chiral (+)-18C6TA than the l isomer. [10] Chiral discrimination requires the cooperative interaction of several weak forces, such as dipole-dipole, hydrophobic, electrostatic, van der Waals, and hydrogen-bonding interactions.…”

Chiral Separation for Enantiomeric Determination in the Pharmaceutical Industry

“…A different type of crown ether used to separate enantiomers is derived from 18-crown-6 tetracarboxylic acid, covalently immobilised on silica gel via the reaction between 18-crown-6 tetracarboxylic acid and amino propyl silica gel [51,52]. NMR spectroscopy of the complex between the 18-crown-6 tetracarboxylic acid and phenylglycine or phenylglycine methyl ester showed for the chiral recognition of the more stable complex the following interactions: 1) three -NH … O hydrogen bonds in a tripod arrangement between the polyether oxygens of 18-crown-6-tetra carboxylic acid and the ammonium moiety of the enantiomer; 2) a hydrophobic interaction between the polyether ring of 18-crown-6-crown ether and the phenyl ring of the enantiomer; 3) hydrogen bonding between the carboxylic acid of the crown ether and the carbonyl oxygen of the enantiomer [53]; 4) if the analyte contains an aromatic moiety, in some instances CH - interactions are possible from the carbon adjacent to the carboxyl group and the aromatic moiety. Table 6.4 gives the HPLC mobile phase composition for the enantiomeric separation of selected compounds on the CSP containing (+/-)-18-crown-6 ether.…”