Enantiomerization of chiral 2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c][1,2,4] benzothiadiazine 5,5-dioxide by stopped-flow multidimensional HPLC.
An on-column stopped-flow multidimensional HPLC (sfMDHPLC) procedure using two chiral stationary phases (CSPs) and one achiral C18 column was developed for the determination of rate constants and free energy barriers of enantiomerization of (+/-)(R,S)-2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c][1,2,4]benzothiadiazine 5,5-dioxide. Moreover, a stopped-flow HPLC (sfHPLC) method previously developed was applied to the determination of kinetic parameters of enantiomerization of the above compound in the presence of a CSP. The individual enantiomers of the studied compound were isolated in parallel by preparative HPLC and the rate constants and free energy barriers of enantiomerization were determined in different solvents (off-column method). The data obtained by sfMDHPLC, sfHPLC and off-column methods were compared. The (S) enantiomer of the studied compound (S18986) was prepared by asymmetric synthesis and subsequently purified by preparative HPLC, followed by the determination of rate constants and free energy barriers of enantiomerization in different buffer solutions at pH 2-9.3.
Cannazza
Giuseppe
G
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Modena e Reggio Emilia, Via Campi 183, 4100 Modena, Italy. cannazza.giuseppe@unimore.it
Carrozzo
Marina M
MM
Braghiroli
Daniela
D
Parenti
Carlo
C
D001581:Benzothiadiazines / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D010087:Oxides / Q000737:chemistry*; D013237:Stereoisomerism
C538975:2,3,3a,4-tetrahydro-1H-pyrrolo(2,1-c)(1,2,4) benzothiadiazine 5,5-dioxide; D001581:Benzothiadiazines; D010087:Oxides