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Preparative Enantioseparation of ( RS )‐Baclofen: Determination of Molecular Dissymmetry
Author(s) -
Vashistha Vinod Kumar,
Bhushan Ravi
Publication year - 2015
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.22428
Subject(s) - diastereomer , chemistry , elution , high performance liquid chromatography , triazine , chromatography , absolute configuration , chiral derivatizing agent , enantiomer , chiral column chromatography , stereochemistry , organic chemistry
The present work reports preparative enantioseparation of ( RS )‐baclofen using thin‐layer chromatography (TLC) and high‐performance liquid chromatography (HPLC). Diastereomers were synthesized using a new monochloro‐s‐triazine‐based chiral derivatizing reagent (CDR), namely, N‐(4‐chloro‐6‐piperidinyl‐[1,3,5]‐triazine‐2‐yl)‐L‐phenylalanine, under microwave irradiation . Acetonitrile‐0.1% aq. triflouroacetic acid in gradient elution mode and CH 3 OH‐CH 2 Cl 2 (4:5; v/v) were successful as mobile phase in HPLC and TLC, respectively. The two diastereomers were isolated by preparative TLC. Molecular dissymmetry was established by developing the lowest energy optimized structures of the diastereomers based on Density Functional Theory and with the help of 1 H NMR showing anisotropic effect associated with aromatic ring of s ‐triazine (in the CDR). The configuration of diastereomers was established as [L‐Phe‐( R )‐Bac] and [L‐Phe‐( S )‐Bac], where the first notation refers to the configuration of chiral auxiliary (of the CDR) and the second to that of the analyte Bac. Limits of detection were found to be 0.056 and 0.061 ng mL −1 , respectively, for the two diastereomers. Determination of absolute configuration of the two diastereomers lent support to the elution order and separation mechanism. Chirality 27:299–305, 2015 . © 2015 Wiley Periodicals, Inc.