Amylose derivatives

As mentioned previously, cellulosic phases as well as amylosic phases have also been used extensively for enantiomeric separations more recently (89,90). Most of the work ia this area has been with various derivatives of the native carbohydrate. The enantioresolving abiUties of the derivatized cellulosic and amylosic phases are reported to be very dependent on the types of substituents on the aromatic moieties that are appended onto the native carbohydrate (91). Table 3 fists some of the cellulosic and amylosic derivatives that have been used. These columns are available through Chiral Technologies, Inc. and J. T. Baker, Inc. 

Examples with other Pirkle-type CSPs have also been described [139, 140]. In relation to polysaccharides coated onto silica gel, they have shown long-term stability in this operation mode [141, 142], and thus are also potentially good chiral selectors for preparative SFC [21]. In that context, the separation of racemic gliben-clamide analogues (7, Fig. 1-3) on cellulose- and amylose-derived CSPs was described [143]. 

Cellulose derivatives Amylose derivatives Brush-type... 

Amylose derivatives NSAIDs, protease inhibitors, P-blockers, benzodiazepines... 

Okamoto et al [85] performed the optical resolution of primaquine and other racemic drugs by high performance liquid chromatography using cellulose and amylose tris-(phenylcarbamate) derivatives as chiral stationary phases. Primaquine and other compounds were effectively resolved by cellulose and/or amylose derivatives having substituents such as methyl, tertiary butyl, or halogen, on the phenyl groups. 

Cellulose and amylose derivative CSPs are mostly used, in the normal-phase mode, with n-hexane-based mobile phases containing some alcohol as modifier. Chromatographic performances, retention and selectivity, are reported to be affected by the composition of the mobile phase... 

Fig. 1.—Preparative Separation of Amylose-derived Oligosaccharides on Aminopropyl Silica-gel L.c. Column (2 x 25 cm) Eluted with 11 9 Acetonitrile-Water at 12 mL/min. [Sample size, 500 mg pressure, 7 MPa. Refiractive index detection at I28x. Each numbered peak was collected at 86-98% purity. Numbers above peaks refer to d.p. values. See also. Ref. 8.]... 

FIGURE 10.13 Helical structural arrangement of amylose derived from alpha-o-glucose units. 

The triester and triphenylcarbamate derivatives of amylose were prepared as in the case of cellulose, but the triester derivatives of amylose are not useful for chiral resolution. Therefore, the triester derivatives of amylose have not been studied extensively. The chemical structures of the triphenylcarbamate derivatives are shown in Fig. 3. Similarly, the chiral resolution power of amylose derivatives was studied by introducing electron-donating and electron-withdrawing groups on the phenyl ring of the amylose derivatives [21-24],... 

As noted earlier, not all the prepared derivatives of cellulose and amylose are useful CSPs. Therefore, some of the useful derivatives of cellulose and amylose were selected and commercialized. The cellulose and amylose CSPs were commercialized by Daicel Chemical Industries of Tokyo. About 20 derivatives of cellulose and amylose are commercially available, as shown in Figure 8, with their chemical and trade names. The trade name of the cellulose and amylose derivatives are Chiralcel and Chiralpak, respectively. An R added to the end of a Chiralcel or Chiralpak trade name denotes a reversed-phase nature CSP. These CSPs are available in stainless steel columns of different dimensions and with different particle sizes. Generally the CSPs are available in the following range of column sizes and particle sizes (in parentheses) 25 cm x 0.46 cm... 

FIGURE 6 Preparation of amylose-derived CSPs in which the chiral selector is fixed to the matrix by the reducing terminal residues. (From Ref. 52.)... 

Unit cell dimensions of different polymorphs of amylose and amylose derivatives. All unit cells contain 2 chains except Va-BuOH and A- and B-amyloses, which contain 1+ chains. 

The majority of preparative separations undertaken at Ultrafine have used chiral stationary phases based on either cellulose or amylose derivatives. In one project 500 mg of salts of both the (R,R)- and (S,S)-Formoterol (6) enantiomers were prepared using an OJ column with a resulting ee of >97%.45 A loading of 200 mg/mL on a semipreparative column was achievable without loss of resolution or purity relative to the racemate. 

The mechanism of molecular recognition and chiral discrimination of cellulose-and amylose-derived chiral selectors is difficult to study due to the complexity of the macromolecule and their multiple binding sites. However, some knowledge of binding mechanisms exist for selected selectands from NMR spectroscopy ] 165.166], molec-... 

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