LC enantioseparation of active pharmaceutical ingredients using rationally synthesized CDRs and chiral molecules with high molar absorptivity.

The synthesis of optically active compounds requires determination of ee, er, and enantiomeric purity. The aim of the present paper is to review the synthesis of several chiral derivatizing reagents (CDRs) in a rational manner, which were successful for the separation and isolation of enantiomers of a variety of active pharmaceutical ingredients and other important and useful racemates. Besides, the application of (i) certain enantiomerically pure amines, either directly or by incorporating each of them as chiral auxiliary in difluorodinitrobenzene or cyanuric chloride moieties to construct the CDR, (ii) (S)-ketoprofen and (S)-levofloxacin as chiral platforms, and (iii) a few isothiocyanates, have been suitably included. Attention is drawn to the use of water micellar mobile phase as the "green" RP-HPLC method and the use of simple achiral derivatization with ninhydrin, particularly. Synthesis of CDRs and their application for enantioseparation of racemates and detagging of certain chromophoric reagent components for obtaining native enantiomers are other interesting features included herein. The methods can be easily used to determine and control enantiomeric purity with advantages over a variety of commercial chiral phases. This comprehensive review not only highlights innovative methodologies for enantioseparation but also underscores their practical applications in controlling and ensuring the enantiomeric purity of pharmaceutical compounds.

Sethi S ，Bhushan R 《-》

'Ab Ovo' Chiral Phases and Chiral Reagents for Liquid Chromatographic Separation and Isolation of Enantiomers.

The de-novo approach of mixing chirally pure reagents or Cu(II)-L-amino acid complexes in the slurry of silica gel for preparing TLC plates was reported from author's laboratory and was successful for separation and isolation of enantiomers. Using high molar absorptivity molecules, e. g., 1,5-difluoro-2,4-dinitrobenzene and cyanuric chloride, more than 38 new chiral derivatizing reagents were synthesized in our laboratory by straightforward nucleophilic substitution with simple chiral auxiliaries. Besides, (S)-naproxen, (S)-ketoprofen, and (S)-levofloxacin were used as chiral platforms. A conceptual approach using both achiral phases in chromatography for enantioseparation was also adopted. 1 H NMR and DFT based software were used to explain structures of non-covalent and covalent diastereomeric pairs and determination of configuration and separation mechanism. The methods can be easily used to determine and control enantiomeric purity with advantages over a variety of commercial chiral phases.

Bhushan R 《-》

Amino acids as chiral auxiliaries in cyanuric chloride-based chiral derivatizing agents for enantioseparation by liquid chromatography.

This review summarizes and critically evaluates the recent research on application of amino acids and amino acid amides as chiral auxiliaries in cyanuric chloride (CC) based chiral derivatizing agents (CDRs), used in the indirect approach for enantiomeric resolution. Methods of synthesis of such CDRs, methods for synthesis of diastereomers of a variety of racemic compounds and parameters of liquid chromatographic separation, along with their prospects and their limitations in indirect enantioresolution, are discussed. Application of the said CDR(s) and the technical approach to be used that are discussed should be beneficial for control of enantiomeric purity in pharmaceutical industry, verification of enantiomeric ratio of commercial formulations and the development of methods for indirect resolution of a variety of chiral compounds. Derivatization methods are particularly required when a chromophore is to be introduced in low UV absorbing molecules, for their detection.

Batra S ，Bhushan R 《-》

Sustainable solutions for direct TLC enantioseparation with in-home thought-out, prepared/modified chiral stationary phases.

Bhushan R 《-》

Application of cyanuric chloride-based six new chiral derivatizing reagents having amino acids and amino acid amides as chiral auxiliaries for enantioresolution of proteinogenic amino acids by reversed-phase high-performance liquid chromatography.

Bhushan R ，Dixit S 《-》