Enantiomers cyclodextrins, glycopeptide

Chiral mobile phase additives provide a more versatile and cost-effective approach for enantiomer separations in thin-layer chromatography. Typically, chemically bonded layers with cyclodextrin and its derivatives, bovine serum albumin, or macrocyclic glycopeptides are used as chiral additives in the reversed-phase mode [59,60,172-178]. For [5- and y-cyclodextrins and their derivatives, a 0.1 to 0.5 M aqueous methanol or acetonitrile solution of the chiral selector is used as the mobile phase. Bovine serum albumin is generally used at concentrations of 1-8 % (w/v) in an aqueous acetate buffer of pH 5 to 7 or in a 0.5 M acetic acid solution, in either case with from 3-40 % (v/v) propan-2-ol (or another aliphatic alcohol), added to control retention. Enantioselectivity usually increases with an increase in concentration of the chiral selector, and may be non existent at low concentrations of the chiral selector. 

In 1971, Davankov et al. achieved the first baseline separation of enantiomers using a small molecule-based CSP consisting of L-proline [1], Since then, a wide range of chiral small compounds, which include amino acids, cyclodextrins, macrocyclic glycopeptides, cinchona alkaloids, crown ethers, jt-basic or rt-acidic aromatic compounds, etc., have been used as CSPs [2—6], On the other hand, the polymer-based CSPs are further divided into two categories, i.e., synthetic and natural chiral polymers [7, 8]. Typical examples of the synthetic polymers are molecularly imprinted polymer gels, poly(meth)acrylamides, polymethacrylates, polymaleimides, and polyamides, and those of the natural polymers include polysaccharide derivatives and proteins. 

There are many classes of CSPs applicable in different mobile-phase modes. In particular, CSPs based on derivatized polysaccharides, native and derivatized cyclodextrins, macrocyclic glycopeptides, and Pirkle-type chiral selectors operate quite well in four separation modes, i.e RP, polar organic phase, NP, and super- or subcritical fluid chromatography (SFC) conditions. It is common that a chiral compound can be separated on the same CSP in more than one separation mode [58, 160, 166, 170-176]. For example, Nutlin-3, a small molecule antagonist of MDM2, has been baseline resolved from its enantiomer in all four mobile-phase conditions (Fig. 16) [170]. Multimodal enantioseparation on the same CSP would be greatly beneflcial for chiral method development in pharmaceutical industry. 

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