Chiral stationary phases optically active polymers

The synthesis of optically active polymers was tackled with the purpose not only of clarifying the mechanism of polymerization and the conformational state of polymers in solution, but also to explore the potential of these products in many fields as chiral catalysts, as stationary phases for chromatographic resolution of optical antipodes, for the preparation of liquid crystals, and so on. 

Among the possible uses of optically active polymers, the preparation of stationary chiral phases for chromatographic resolution of enantiomers is the... 

Anionic Catalysis Several bulky methacrylates afford highly isotactic, optically active polymers having a single-handed helical structure by asymmetric polymerization. The effective polymerization mechanism is mainly anionic but free-radical catalysis can also lead to helix-sense-selective polymerization. The anionic initiator systems can also be applied for the polymerization of bulky acrylates and acrylamides. The one-handed helical polymethacrylates show an excellent chiral recognition ability when used as a chiral stationary phase for high-performance liquid chromatography (HPLC) [97,98]. 

Isocyanide Polymers Bulky isocyanides give polymers having a 4 1 helical conformation (115) [154]. An optically active polyisocyanide was first obtained by chromatographic resolution of poly(f-butyl isocyanide) (poly-116) using optically active poly((S)-sec-butyl isocyanide) as a stationary phase and the polymer showing positive rotation was found to possess an M-helical conformation on the basis of CD spectral analysis [155,156]. Polymerization of bulky isocyanides with chiral catalysts also leads to optically active polymers. 

Yashima, E., Matsushima, T., Nimura, T., and Okamoto, Y. (1996) Enantioseparation on optically active stereoregular polyphenylacetylene derivatives as chiral stationary phase for HPLC, Korea Polym. J. 4, 139-146. 

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]. 

One of the most studied polymerization systems employs alkyllithium initiators that are modified by chiral amine ligands for the polymerization of sterically bulky methacrylates [8,38,39,40,41], acrylates [42],crotonates [43], and acrylamides [44]. A primary example is the reaction of triphenylmethyl methacrylate with an initiator derived from 9-fluorenyllithium and (-)-sparteine (3) at -78 °C (Scheme 4). The resultant isotactic polymer is optically active, and is postulated to adopt a right-handed helix as it departs from the polymerization site. This polymer has been particularly successful as a chiral stationary phase for the chromatographic resolution of atropisomers [8]. Many modifications of the or-ganolithium initiator/chiral ligand system have been explored. Recently, Okamo-to has applied enantiopure radical initiators for the enantioselective polymerization of bulky methacrylate monomers [45]. 

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

PA-7A (Figure 5.13) polymers obtained employing DBTL and TEA as catalysts, respectively. The authors claim that since these polymers are optically active and have amino acids in the polymer architecture, they are likely biodegradable, and are therefore classified as environmentally friendly polymers. Potential application can be found for the amino acid based pol)miers as the chiral stationary phases for the resolution of enantiomers in chromatographic techniques, drug delivery and biomaterials. 

Chiral separation of flavonoids has also been carried out by chromatographic systems by using a chemically bonded chiral stationary phase or by the addition of chiral mobile phase additives (reviewed by Yanez et al. ). These chiral polymer phases can be further subdivided into polysaccharide-derived columns, and cyclodextrin and mixed cyclodextrin columns. With regard to chiral mobile phase additives, the addition of an optically active molecule to the mobile phase can facilitate separation of enantiomers on conventional stationary phases. Cyclodextrin as a chiral additive is widely used to separate enantiomers mainly by capillary electrophoresis (CE), as discussed in Section 3.6.2.I. Table 3.7 summarizes the most habitual HPLC procedures employed for the analysis of various classes of food flavonoids. 

In contrast, liquid chromatography lends itself to chiral separations and there are two basic procedures for separating optically active solutes. Firstly, reversed phase chromatography can be employed and a chiral substance can be added at low concentrations in the mobile phase. The chiral additive will be absorbed onto the surface of the reversed phase and act as an adsorbed stationary phase having chiral activity. This approach makes chiral detection more difficult, as it provides a background of optical activity in the mobile phase that will be many orders greater than that from the chirally active solutes. This is inevitably accompanied by a high noise level and consequent poor sensitivity. The second approach is to employ specific chirally active materials that are bonded to a silica or polymer surface to provide chirally specific interactions with the solutes. 

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