Amylose carbamate derivatives

Carbamate derivatives (Table 1) of cellulose, chitin, amylose, amylopectin, and dextran were prepared using the isocyanates described in Part A of the Experimental Section. Amylose, amylopectin, dextran, and cellulose were obtained from Polysciences, Inc. and used without further purification. Chitin, obtained from Eastman Kodak, was decalcified and deproteinated by the method reported by Haye r prior to use. 

Cellulose, Amylose and Other Polysaccharide Carbamate Derivatives... 

FIGURE 3 The chemical structures of cellulose benzoate, amylose benzoate, and carbamate derivatives. (From Ref. 32.)... 

Y. Okamoto, M. Kawashima, and K. Hatada, Optical resolution of racemic drugs by chiral HPLC on cellulose and amylose tris(phenyl-carbamate) derivative, J. Liquid Chromatogr., 11 2147 (1988). 

Natural polymers like cellulose and amylose comprise the Type IIIA CSPs, but the mechanical stability of these packings is not sufficiently adequate to be used as a chromatographic sorbent. More satisfactory sorbents have been obtained by chemically modifying them as ester or carbamate derivatives and then coating them onto large-pore silica (300 A) [276]. These CSPs are marketed under the trade names ChiralCel (cellulose) and ChiralPak (amylose). These packings have a wide scope of applications, good stability, and use on a preparative scale. 

Accordingly, the spectrum of applicability of these CSPs can be derived. It appears that cellulose- and amylose-carbamate CSPs are excellent for the enantioseparation of SAs with hydrogen donor and/or acceptor sites (amides, carbamates, sulphonamides, hydroxy groups) as well as aromatic moieties, advantageously in combination with bulky groups close to the interaction sites. Due to the broad range of applicability a more detailed list of resolvable SAs would extend this report. However, further information is available from the application guide [172], from review articles [47,99,1(X), and from recently published enantioseparations (Table 9.4). 

Okamoto and Kaida 99j as well as other research groups also reported the enan-tiodiscrimination ability of CSPs derived from other polysaccharides than cellulose or amylose, including chitosan derivatives 1109.155,1-56], heparin [174], and some others. In some cases chitosan, 3,5-dimethylphenyl carbamate derivatives have shown higher discrimination capability than the cellulose or amylose analogues. 

Expansion of these investigations to other types of polysaccharide derivatives led to the development of silica-coated versions of cellulose and amylose carbamates and benzoates [100-102]. These CSPs showed particularly versatile chiral recognition profiles, resolving an extremely broad assortment of chiral analytes. Several of these CSPs have been commercialized by Daicel Chemical Industries, Ltd., the most important ofwhich are depicted in Fig. 7.5. 

To address development of chiral separations by SFC, Villeneuve and Anderegg have developed an SFC system using automated modifier and column selection valves. Columns (250 x 4.6 mm i.d., 10 pm) packed with Chiralpak AD, Chiralpak AS amylose derivative, Chiralcel OD cellulose carbamate derivative, and Chiralcel OJ cellulose ester derivative (Chiral Techologies, Exton, PA) were connected to a column-switching valve. Candidate samples were run successively on each column using fixed isocratic, isobaric, and isothermal conditions of 2 ml/min, 205 atm pressure, and 40 °C with the vari-... 

The ester and carbamate derivatives of cellulose and amylose are among the most successful and versatile chiral stationary phases for liquid and supercritical fluid chromatography [1,4,28,107-109]. These phases are prepared by reaction of the poly(saccharide) with an acid chloride (ester derivative) or phenylisocyanate (carbamate... 

In practice, it has been found that certain derivatives e.g. tris (3,5-dimethylphenyl carbamate) render the coating less culnerable to solvent dissolution. As a consequence this stationary phase can be used with buffered methanol/water or acetonitrile/water with certain care being taken. Therefore, the tris(3,5-dimethylphenyl carbamate) derivatives of both cellulose and amylose can, with caution, be used in the reversed phase mode. As example of a chiral separation using the different modes is shown in figure 8.6. 

Among optically active polymers, polysaccharide derivatives are particularly valuable. Polysaccharides such as cellulose and amylose are the most readily available optically active polymers and have stereoregular sequences. Although the chiral recognition abilities of native polysaccharides are not remarkable, they can be readily converted to the esters and carbamates with high chiral recognition abilities. The chiral recognition mechanism of these derivatives has been clarified to some extent. 

Table I lists physical data for a number of the carbamate and ester derivatives of cellulose, chitin, amylose, amylopectin, and dextran synthesized as described in the Experimental Section. The solubility of the polysaccharide starting materials as well as that of the produced derivatives allows for macromolecular characterization through techniques including UV, NMR, IR, high pressure liquid chromatography, etc.

The most useful CSPs for the resolution of many varied, structurally different racemates are the following the peracetates, benzoates (and derivatives) and carbamates (and derivatives) of cellulose and amylose coated on wide pore silica gel. Some of these polymer derivatives are also potentially useful as pure polymeric bead material, but mainly for preparative purposes. 

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