High-performance liquid chromatographic determination of α-aminonitrile enantiomers after derivatization with o-phthalaldehyde and chiral thiols

• Published in: Journal of Chromatography A Vol. 1055; no. 1; pp. 235 - 239
• Main Authors: Duchateau, A.L.L., Boesten, J.M.M., Christis, B., Eijnthoven, F., Henderickx, H.J.W.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 05.11.2004; Elsevier
• Subjects: Analysis; Analytical biochemistry: general aspects, technics, instrumentation; Analytical chemistry; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Chemistry; Chromatographic methods and physical methods associated with chromatography; Chromatography, High Pressure Liquid - methods; Derivatization,LC; Enantiomer separation; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; General pharmacology; Mass Spectrometry; Medical sciences; Molecular modelling; Nitriles - analysis; o-Phthalaldehyde - chemistry; Other chromatographic methods; Pharmacology. Drug treatments; Spectrophotometry, Ultraviolet; Stereoisomerism; Sulfhydryl Compounds - chemistry; α-Aminonitrile; Molecular modelling; α-Aminonitrile; Derivatization,LC; Enantiomer separation; Thiol; Separation; Optical resolution; Enantiomer; LC; α-Aminonitrile; HPLC chromatography; Enantiomer separation; Molecular modelling; Derivatization; Liquid chromatography; Determination; Aminonitrile; Derivatization; Modeling
• ISSN: 0021-9673
• DOI: 10.1016/j.chroma.2004.08.132

o-Phthalaldehyde in combination with chiral thiols is described as a chiral reagent for the resolution of the enantiomers of α-H-α-aminonitriles and α-alkyl-α-aminonitriles. Separation of the resulting diastereomers was carried out by reversed-phase chromatography and the derivatives were detected at UV 340 nm. The identity of the diastereomeric derivatives was confirmed by LC–MS. Among the chiral thiols tested, N-acetyl- d-penicillamine and β-mercaptoisobutyric acid gave the best resolution for the α-aminonitriles studied. For quantitative enantiomeric excess determination, β-mercaptoisobutyric acid was chosen as this thiol could be obtained in high enantiomeric purity from a commercial source. The rate of the reaction of various α-aminonitriles with o-phthalaldehyde and β-mercaptoisobutyric acid was studied. The accuracy of the method was investigated by a comparison of theoretical and measured enantiomeric excess.