On-line racemization by high-performance liquid chromatography.
An on-column stopped-flow bidimensional recycling HPLC procedure was developed to obtain an enantiomeric enrichment starting from a racemic mixture. The method developed was applied to two chiral compounds of pharmaceutical interest, (+/-)(R,S)-2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c][1,2,4]benzothiadiazine 5,5-dioxide (1) and (+/-)-7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide ((+/-)IDRA21, (2)), since the pharmacological activity of the two benzothiadiazine derivatives investigated has been ascribed to only one enantiomer. Starting from a racemic mixture it was possible to obtain about 95% of pure enantiomer. The procedure was applied both in reverse-phase mode and in normal-phase mode. The scaled up and automatization of the novel analytical HPLC procedure represents a powerful tool to obtain pure enantiomer starting from racemic compounds without cumbersome stereoselective synthesis or expensive enantiopurification processes.
Cannazza
Giuseppe
G
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Modena e Reggio Emilia, 4100 Modena, Italy. giuseppe.cannazza@unimore.it
Carrozzo
Marina M
MM
Battisti
Umberto
U
Braghiroli
Daniela
D
Parenti
Carlo
C
D001581:Benzothiadiazines / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D009862:Online Systems; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D013237:Stereoisomerism
D001581:Benzothiadiazines; D004364:Pharmaceutical Preparations