Enantiomeric Separation of Racemic 4‐Aryl‐1,4‐Dihydropyridines and 4‐Aryl‐1,2,3,4‐Tetrahydropyrimidines on a Chiral Tetraproline Stationary Phase

Abstract

The chromatographic chiral resolution of 4-aryl-1,4-dihydropyridines (1-32), 4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidines (33-38), and 4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidines (39-41) was studied on a tetraproline-immobilized chiral column synthesized in our lab. This tetraproline chiral stationary phase can resolve most of these compounds. The 4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidines (33-38) and 4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidines (39-41) were more efficiently resolved than the racemic 4-aryl-1,4-dihydropyridines on the tetraproline chiralstationary phase. Analytes with 5,5-dimethyl groups (39-41) were less efficiently resolved than analytes without 5,5-dimethyl substituents (1-16). The 4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidines (39-41) without a sulfur atom were much more efficiently resolved than 4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidines (33-38). No obvious electronic effects on the resolution of any of these analytes (1-41) were observed on the tetraproline chiral stationary phase. The tetraproline chiral stationary phase separated enantiomers mainly via hydrogen bonding interactions.

Enantiomeric Separation and Simulation Studies of Pheniramine, Oxybutynin, Cetirizine, and Brinzolamide Chiral Drugs on Amylose‐Based Columns

“…Various factors such as drug concentration, pH, ionic concentration, temperature, etc., are responsible for controlling the racemization process . It is a well‐known fact that one of the enantiomers is pharmaceutically active while the other may be inactive or toxic or ballast, leading to various side effects, toxicity, and problems in the human body . US‐FDA, European Committee for Proprietary Medicinal Products, Health Canada, and Pharmaceutical and Medical Devices Agencies of Japan have banned the marketing of all racemic drugs .…”

“…4 It is a well-known fact that one of the enantiomers is pharmaceutically active while the other may be inactive or toxic or ballast, leading to various side effects, toxicity, and problems in the human body. 5,6 US-FDA, European Committee for Proprietary Medicinal Products, Health Canada, and Pharmaceutical and Medical Devices Agencies of Japan have banned the marketing of all racemic drugs. [7][8][9] The enantiomeric differences at the pharmacokinetic level are mainly because of stereoselective drugs binding, absorption, clearance, excretion, etc.…”

Liquid Chromatographic Resolution of Racemic 2‐Oxazolidinones and their Analogs on Seven Pirkle‐Type Chiral Stationary Phases

“…[2][3][4][5] The chiral separation of nonoxazolidinone samples has been previously reported. [6][7][8][9][10][11][12][13][14] Separation of DUP-105, ZTR-5, and 3-amino-2-oxazolidinone derivatives was performed on polysaccharide columns; 4,5,15 4-benzyl-2-oxazolidinone, 5,5-dimethyl-4-phenyl-2-oxazolidinone, 4-benzyl-5,5-dimethyl-2-oxazolidinone, 4-diphenylmethyl-2-oxazolidinone, cis-4,5-diphenyl-2-oxazolidinone, 4-methyl-5-phenyl-2-oxazolidinone, and 4-benzyl-3-propionyl-2-oxazolidinone were resolved on glycopeptide columns; 16,17…”