Chiral stationary phases synthetic polymers

Another type of synthetic polymer-based chiral stationary phase is formed when chiral catalyst are used to initiate the polymerisation. In the case of poly(methyl methacrylate) polymers, introduced by Okamoto, the chiraUty of the polymer arises from the heUcity of the polymer and not from any inherent chirahty of the individual monomeric subunits (109). Columns of this type (eg, Chiralpak OT) are available from Chiral Technologies, Inc., or J. T. Baker Inc. 

A few synthetic helical polymers are known to act as chiral selectors.7a,918d l8k i9d i9h ancj are widely used as chiral stationary phases (CSP) in gas or liquid chromatography.73,53 Recently, it has been reported that the preference of one helical sense in isotropic solution can be induced by some interaction between optically inactive polymers and chiral solvents/additives. Examples of this include poly(n-hexyl isocyanate)18d l8k and poly(phenylacetylene)s bearing functional group.19d 19h The polysilane derivatives also show chiral recognition ability in solution at room temperature. Poly(methyl-ft-pinanylsilane) includes two chiral centers per bulky hydrophobic pinanyl side group28 and... 

I.6.2. Chiral Stationary Phases (CSPs) Based on Synthetic Polymers... 

A third type of synthetic polymer-based chiral stationary phase, developed hy Blaschke. is produced when a chiral selecior is either incorporated within the polymer network or attached as pendant groups onto the polymer matrix. Both arc analogous to methods used lo produce polymeric chiral stationary phases for gc. 

The most popular and commonly used chiral stationary phases (CSPs) are polysaccharides, cyclodextrins, macrocyclic glycopeptide antibiotics, Pirkle types, proteins, ligand exchangers, and crown ether based. The art of the chiral resolution on these CSPs has been discussed in detail in Chapters 2-8, respectively. Apart from these CSPs, the chiral resolutions of some racemic compounds have also been reported on other CSPs containing different chiral molecules and polymers. These other types of CSP are based on the use of chiral molecules such as alkaloids, amides, amines, acids, and synthetic polymers. These CSPs have proved to be very useful for the chiral resolutions due to some specific requirements. Moreover, the chiral resolution can be predicted on the CSPs obtained by the molecular imprinted techniques. The chiral resolution on these miscellaneous CSPs using liquid chromatography is discussed in this chapter. 

The use of chiral stationary phases (CSP) in liquid chromatography continues to grow at an impressive rate. These CSPs contain natural materials such as cellulose and starch as well as totally synthetic materials, utilizing enantioselective and retentive mechanisms ranging from inclusion complexation to Ti-electron interactions. The major structural features found in chiral stationary phases include cellulose, starch, cyclodextrins, synthetic polymers, proteins, crown ethers, metal complexes, and aromatic w-electron systems. 

Mechanistic considerations (e.g., the extensive work published on brush-type phases) or the practitioner s experience might help to select a chiral stationary phase (CSP) for initial work. Scouting for the best CSP/mobile phase combination can be automated by using automated solvent and column switching. More than 100 different CSPs have been reported in the literature to date. Stationary phases for chiral pSFC have been prepared from the chiral pool by modifying small molecules, like amino acids or alkaloids, by the deriva-tization of polymers such as carbohydrates, or by bonding of macrocycles. Also, synthetic selectors such as the brush-type ( Pirkle ) phases, helical poly(meth) acrylates, polysiloxanes and polysiloxane copolymers, and chiral selectors physically coated onto graphite surfaces have been used as stationary phases. 

Optically active synthetic polymers such as poly(trityl methacrylate) supported on silica gel [7,8] as well as poly(ethylene glycol dimethacrylate) cross-linked in the presence of an optically active template [9] have found general use as chiral stationary phases for the optical resolution of various racemates by chromatography. A current area of investigation concerns the use of optically active polymers as reagents and catalysts for asymmetric synthesis [10,11,12]. 

Shea, K.J. Molecular imprinting of synthetic network polymers the de novo synthesis of macromolecular binding and catalytic sites. Trends. Polym. Sci. 1994, 2, 166-173. Sellergren, B. Imprinted chiral stationary phases in high-performance liquid chromatography. J. Chromatogr. A 2001, 906, 227-252. 

Andersson, L.I. O Shannessy, D.J. Mosbach, K. Molecular recognition in synthetic polymers preparation of chiral stationary phases by molecular imprinting of amino acid amides. J. Chromatogr. 1990, 513, 167-179. 

Nakano T (2001) Optically active synthetic polymers as chiral stationary phases in HPLC. Journal of Chromatography A 906 205-225. 

Chiral stationary phases that are currently available can be classified into those containing cavities (cellulose derivatives, cyclodextrins, synthetic polymers, crown ethers, and chiral imprinted gels), affinity phases (bovine serum albumin, human serum albumin, a-glycoprotein, enzymes), multiple hydrogen-bond phases, Ti-donor and Ti-acceptor phases, and chiral ligand exchange phases. This classification scheme was used in a review that gave numerous pharmaceutical examples of separation by... 

According to their chemical structures, CSPs can be divided into three different groups. A multitude of chiral stationary phases is derived from (modified) natural or synthetic polymers, e.g., the polysaccharides, proteins or polyacrylamides. A second type of selectors is based on large chiral ring systems, such as cyclo-dextrins, macTocycKc antibiotics, and crown ethers. The last group comprises moleailes of small and medium size, such as amino acids and their derivatives, alkaloids, and fuUy synthetic selectors. 

The helical polytriphenylmethyl methacrylate was the first synthetic chiral polymer able to separate a very limited number of enantiomers [28]. Recently a fully synthetic chiral stationary phase based on polymerized diacryloyl derivative of fra s-l,2-diaminocyclohexane [either (R, R) or (S, S)] bonded to silica gel in the form of a very thin layer was proposed as a new LC CSP [29]. This CSP could not resolve many enantiomeric pairs. However, when it could resolve a racemate, it was shown that the amount that could be loaded was much larger than that on most other CSPs. It means that the number of active sites is large. Hydrogen bonds were found to be pivotal in the chiral recognition mechanism of this CSP. The enan-tioselectivity was adjusted by the methanol content in the organic mobile phase. Polysodium A-undecanoyl-L-leucyl-leucinate (poly-SULL) and —L-leucyl-valinate... 

Suedee, R., Songkram, C., Petmoreekul, A., Sangkunakup, S., Sankasa, S. and Kongyarit, N., Thin-layer chromatography using synthetic polymers imprinted with quinine as chiral stationary phase, J. Planar Chromatogr., 11, 272-276, 1998. 

Aboul-Enein, H.Y., El-Awady, M.I. and Heard, C.M., Direct enantiomeric resolution of some cardiovascular agents using synthetic polymers imprinted with —)S-timolol as chiral stationary phase by thin layer chromatography, Pharmazie, 57, 169-171, 2002. 

Chromatographic enantioseparations may be performed using two methods called direct and indirect. In this former method, chiral stationary phases (polymers of natural origin, protein phases, synthetic polymers with build-in chiral selectors, etc.) are used or appropriate chiral selectors (cyclodextrins, crown ethers, etc.) are added to the mobile phase [7]. 

A CSP consists of a chiral selector, which either alone constitutes the stationary phase or which has been immobilised to a solid phase. The chiral selector is a low molecular weight compound or a polymer, either synthetic or natural. A broad range of CSPs has been developed. Examples of CSPs that have been used successfully include polysaccharides, such as cellulose and its derivatives [6] and cyclodex-trins [7], and proteins, e.g. bovine serum albumin, aj-acid glycoprotein, cellulase, trypsin and a-chymotrypsin [8]. Several different synthetic polymers have also proven to be useful CSPs, for example the Blaschke-type CSPs (polyacrylamides and polymethacrylamides) [9] and the Pirkle-type CSPs [10]. 

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