Indirect enantioresolution of (R,S)-mexiletine by reversed-phase high-performance liquid chromatography via diastereomerization with [(S,S)-O,O'-di-p-toluoyl tartaric acid anhydride], (S)-naproxen and nine chiral reagents synthesized as variants of Marfey's reagent.
Eleven chiral derivatizing reagents (CDRs) were used for preparation of diastereomers of (R,S)-mexiletine containing a primary amino group in close proximity to the stereogenic center. One anhydride, namely [(S,S)-O,O'-di-p-toluoyl tartaric acid anhydride] was synthesized and (S)-naproxen was used as such as the chiral derivatizing reagent. The other nine CDRs were synthesized by substituting one of the fluorine atoms in 1,5-difluoro-2,4-dinitrobenzene with six amino acid amides and three amino acids. The diastereomers were separated by reversed-phase high-performance liquid chromatography. The method was validated for linearity, accuracy, limit of detection and limit of quantification. The limit of detection was found in the range of 10-30  pmol.
Bhushan
R
R
Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee, India. rbushfcy@iitr.ernet.in
Tanwar
Shivani
S
Dixit
Shuchi
S
D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D056148:Chromatography, Reverse-Phase / Q000379:methods*; D004136:Dinitrobenzenes / Q000737:chemistry*; D008801:Mexiletine / Q000737:chemistry / Q000302:isolation & purification*; D009288:Naproxen / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D013644:Tartrates / Q000737:chemistry*
D004136:Dinitrobenzenes; D013644:Tartrates; C422602:di-p-toluoyltartaric acid; D008801:Mexiletine; D009288:Naproxen; C047134:Marfey's reagent; D000409:Alanine