Chiral resolution of the enantiomers of 7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide using high-performance liquid chromatography on cellulose-based chiral stationary phases

Analytical high-performance liquid chromatography (HPLC) methods using deri vatized cellulose chiral stationary phases (CSPs) were developed for the se paration of the enantiomers of 7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzo thiadiazine 1,1-dioxide ((+/-) IDRA21). in previous studies, (+/-) IDRA21 h as been found to have an interesting inhibitory effect on the desensitizati on of alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid (AMP A) receptor and improve cognition in animals. This compound posses one chir al carbon atom, but very little information has been reported on the stereo selectivity of his activity. Therefore resolution of the enantiomers of thi s compound and subsequent identification of stereospecifity in his pharmaco logical actions are clearly matters of interest. The resolution were made u nder normal- and reversed-phase conditions using a mobile phase consisting of n-hexane:2-propanol (70/30, v/v) and water:acetonitrile (60/40, v/v) res pectively, and a CSP of silica-based cellulose tris-3,5-dimethyl-phenylcarb ammate (Chiralcel OD and Chiracel OD-R). The enantiomeric nature of eluates was confirmed by circular dichroism (CD) spectra. A baseline separation (R -s > 1.5) was obtained in both cases. Furthemore the isolation of optical i somers of (+/-) IDRA21 was perfomed using a semipreparative column packed w ith the same cellulose OD CSP. (C) 2000 Elsevier Science B.V. All rights re served.