Chiral stationary phase, separation enantiomeric amides

Chromatographic separatum of enantiomersThe carbamate, ureido, and amide derivatives obtained without racemization from enantiomeric amines, alcohols, and carboxylic acids, respectively (equations T III), with this isocyanate are stable for months and are suitable for gas chromatographic separation using a polymeric chiral stationary phase (derived, for example, from L-valine-(S)-a-phenylethylamide). This methodology permits separation of chiral a- and /1-hydroxy acids and also N-mclhylnmino acids. 

The first example show the separation of enantiomeric amides on a chiral stationary phase (4(a)) and on the same phase but in its liquid-crystalline state (4(b)) (first discovered by Lochmllller and Souter (5)). The enhanced selectivity of the latter is so great that a separation which required about 35,000 plates on a capillary column is reduced to a 100 plate packed column experiment. As a result the practical capacity is increased fom the picogram to the milligram range. 

Van Overbeke, A. Baeyens, W. Van den Bossche, W. Dewaele, C. Enantiomeric separation of amide derivatives of some 2-arylpropionic acids by HPLC on a cellulose-based chiral stationary phase. J.Pharm.Biomed.Anai, 1994, 12, 911-916 [chiral derivatization also, flurbiprofen, ketoprofen, tia-profenic acid]... 

Booth TD, Lough WJ, Saeed M, Noctor TAG, Wainer IW (1997) Enantioselective separation of enantiomeric amides on three amylose-based chiral stationary phases effects of backbone and carbamate side chain chiralities. Chirality 9 173-177... 

Wainer IW, Alembik MC (1986) Resolution of enantiomeric amides on cellulose based chiral stationary phases steric and electronic effects. J Chromatogr 358 85-93 Booth TD, Wainer IW (1996) Investigation of the enantioselective separations of a-alkyl arylctirboxylic acids on an amylose tris(3,5-dimethylphenylcatbamate) chiral stationary phase using quemtitative structure-enantioselective retention relationships (QSERR) identification of a conformationaUy driven chiral recognition mechanism. J Chromatogr A 737 157-169... 

For characterization and exploitation of the diamide-phase system, a chiral diamide, e,g., (Ill) was examined as a modifier in the mobile phase (solvent) in conjunction with a non-bonded (bare) silica. Such a chiral carrier separated enantiomeric N-acyl-d-amino acid esters and amides with separation factors comparable to those for bonded stationary phase systems. The resolution can be as cribed to diastereomeric complexation through amide-amide hydrogen bonding between the amide additive and enantiomeric solute molecules in the carrier solvent, followed by separation of the diastereomeric complexes by the (achiral) silica phase. This process should be applicable as widely as that involving chiral diamide-bonded stationary phase systems. 

Owing to the high thermal and long-term stability, amide phases bonded to polysiloxane are regarded as sensitive materials for the sensoric approach to enantiomeric separation. An important factor for the resolution of the stationary material is the number of dimethylpolysiloxane units between the chiral moieties. More than 200 different amide phases have been synthesised and applied for the discrimination of amino acids, lactate esters and many other substances [10]. 

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