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Evaluation of stereo and chemical stability of chiral compounds
Author(s) -
Cannazza Giuseppe,
Battisti Umberto,
Carrozzo Marina M.,
Brasili Livio,
Braghiroli Daniela,
Parenti Carlo
Publication year - 2011
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.20941
Subject(s) - chemistry , racemization , enantiomer , hydrolysis , aqueous solution , reaction rate constant , chirality (physics) , chiral column chromatography , chemical stability , chromatography , high performance liquid chromatography , analytical chemistry (journal) , organic chemistry , kinetics , physics , chiral symmetry breaking , quantum mechanics , nambu–jona lasinio model , quark
A stopped‐flow bidimensional recycle HPLC (sf‐BD‐rHPLC) configuration has been used to investigate simultaneously the stereo and chemical stability of labile chiral compounds. The single enantiomers of a racemate can be separated on chiral column (first dimension) and each one can be trapped in the achiral column (second dimension) that works as reactor.By filling the achiral column with the appropriate aqueous buffers it is possible to evaluate the stability of the trapped enantiomer toward aqueous buffer itself. It was possible to recycle the reaction products formed in the chiral column (first dimension) where they are separated by a second six valve port. The reaction rate constants were calculated for the different processes occurred in the achiral column by means of corresponding peak areas. The method was applied to a pharmacological active compound: (±)7‐chloro‐5‐ethyl‐3‐methyl‐3,4‐dihydro‐2H‐benzo[1,2,4]thiadiazine 1,1‐dioxide ((±)‐ 1 ) to evaluate enantiostability and hydrolysis in conditions similar to those of biological fluid. A classical batchwise kinetic method was used to calculate rate constants of hydrolysis and enantiomerization at the same temperature and in the same solvents used in sf‐BD‐rHPLC. The good agreement of the results obtained validate the novel procedure developed. Furthermore, the results generated off‐line were used to determine the influence of solvents on the racemization of (±)‐ 1 . Chirality, 2011. © 2011 Wiley‐Liss, Inc.