Carbamate amylose

An hplc assay was developed suitable for the analysis of enantiomers of ketoprofen (KT), a 2-arylpropionic acid nonsteroidal antiinflammatory dmg (NSAID), in plasma and urine (59). Following the addition of racemic fenprofen as internal standard (IS), plasma containing the KT enantiomers and IS was extracted by Hquid-Hquid extraction at an acidic pH. After evaporation of the organic layer, the dmg and IS were reconstituted in the mobile phase and injected onto the hplc column. The enantiomers were separated at ambient temperature on a commercially available 250 x 4.6 mm amylose carbamate-packed chiral column (chiral AD) with hexane—isopropyl alcohol—trifluoroacetic acid (80 19.9 0.1) as the mobile phase pumped at 1.0 mL/min. The enantiomers of KT were quantified by uv detection with the wavelength set at 254 nm. The assay allows direct quantitation of KT enantiomers in clinical studies in human plasma and urine after adrninistration of therapeutic doses. 

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. 

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. 

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.

Figure 3. Structure of cellulose carbamates used as CSPs. Similar are the amylose carbamates, but with a different configuration and conformation of the basic polysaccharide (see also Figure 2).

Cellulose, Amylose and Other Polysaccharide Carbamate Derivatives... 

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. 

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

FIGURE 12 Chromatograms of enantiomeric resolution of nebivolol on amylose carbamate CSPs. (a)-(c) Chiralpak AD with (a) ethanol, (b) 1-propanol, and (c) 2-propanol, (d, e) Chiralpak AD-RH with (d) ethanol and (e) 1-propanol, separately, as the mobile phase. (From Ref. 63.)... 

The E-Z isomerization of an azobenzene unit was employed in an approach towards photocontrol of the chiral recognition event in a membrane.1581 To this end, (4-(phenyl-azo)phenyl carbamate residues were attached to carbamate-protected glucose units of cellulose and amylose. The photomodulation of the chiral recognition was explained by a change in the ordering of the polymer, leading to a change in solubility. 

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. 

The synthetic ( )-calanolide A was resolved into its enantiomers, (+)-calanolide A (1) and ( )-calanolide A, by using a semipreparative chiral HPLC column packed with amylose carbamate eluting with hexane/ethnol (95 5). The ultraviolet detection was set at a wavelength of 254 nm. (+)-calanolide A and its enantiomer (—)-calanohde A were collected, and their chemical structures were identified based on their optical rotations and spectroscopic data, as compared with the corresponding natural and synthesis compounds. 

Figure 22-3. Interaction of two drug enantiomers with amylose carbamate stationary phase. (Reprinted from reference 29, with permission.)...

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