Cellulose derivatives chiral separations

In another study, the authors reported a comparative study of the enantiomeric resolution of miconazole and the other two chiral drugs by high performance liquid chromatography on various cellulose chiral columns in the normal phase mode [79], The chiral resolution of the three drugs on the columns containing different cellulose derivatives namely Chiralcel OD, OJ, OB, OK, OC, and OE in normal phase mode was described. The mobile phase used was hexane-isopropanol-diethylamine (425 74 1). The flow rates of the mobile phase used were 0.5, 1, and 1.5 mL/min. The values of the separation factor (a) of the resolved enantiomers of econazole, miconazole, and sulconazole on chiral phases were ranged from 1.07 to 2.5 while the values of resolution factors (Rs) varied from 0.17 to 3.9. The chiral recognition mechanisms between the analytes and the chiral selectors are discussed. 

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-... 

Van Overbeke, A. Baeyens, W. Van Der Weken, G. Van de Voorde, I. Dewaele, C. Comparative chromatographic study on the chiral separation of the 1-naphthylamine derivative of ketoprofen on cellulose-based columns of different sizes. Biomed.Chromatogr., 1995, 9, 289-290... 

Van Overbeke, A. Baeyens, W. Van den Bossche, W. Dewaele, C. Enantiomeric separation of amide derivatives of some 2-arylpropionic acids by HPLC on a cellulose-based chiral stationary phase. J.Pharm.Biomed.Anai, 1994, 12, 911-916 [chiral derivatization also, flurbiprofen, ketoprofen, tia-profenic acid]... 

Ichida, A. Shibata, T. Cellulose derivatives as stationary phases. In Chromatographic Chiral Separations) Zief, M., Crane, L.J., Eds. Marcel Dekker New York, 1988 Chap. 9. 

Cellulose represents an important polymer, which is most abundant in nature, and serves as a renewable resource in many applications, e.g., fibers, films, paper, and as a composite with other polysaccharides and lignin in wood. Cellulose derivatives will also be used as films and fibers, food additives, thermoplastics, and construction materials, to name just a few. Cellulose and cellulose derivatives have played an important role in the development of the macromolecular concept. So far, little use has been made of the fact that cellulose represents a chiral material except, e.g., in a rare case as stationary material in liquid chromatography for the separation of chiral compounds. Nature ifself uses the chirality of cellulose occasionally, and twisted structures of cellulose molecules are found in cell walls. 

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. 

The Separation of Some Chiral Drugs on Different Cellulose Derivatives... 

Okamato et al. [11] also examined the relative performance of cellulose and amylose derivatives for the separation of a group of racemic drugs. At the same time, they demonstrated generally the versatility of the cellulose based chiral stationary phases for the separation of a range of physiologically active compounds. Examples of such separations are shown in figure 11.13 (A-F). 

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... 

Yashima E, Yamada M, Okamoto Y (1994) An NMR study of chiral recognition relevant to the liquid chromatographic separation of enantiomers by a cellulose derivative. Chem Lett 23 579-582... 

The research listed in Table 2 (81-98) deals mainly with separation problems concerning amino acids, amino acid derivatives, and dipeptides, focusing on the influence of the structure of the chiral support and the eluent temperature on the separation behavior of the racemates. Separation of the aromatic amino acids phenylalanine, P-2-thienylalanine, 4-fluorophenylalanine, and tyrosine could not be achieved on microcrystalline or amorphous cellulose tryptophan isomers, however, could be reproducibly resolved on microcrystalline cellulose layers (83). Lowering the eluent temperature from 30 C to O C enhances enantiomeric resolution. However, developing times of 10 1 h (O C), 7.5 0.5 h (10°C), 5 0.5 h (20°C), and 3.5 h (30°C) have to be tolerated hydrophobic eluent combinations further enhance separation, because they improve formation of the helical cellulose conformation (87). Separation of racemic 3,4-dihydroxyphenylalanine, tryptophan, and 5-hydroxy-tryptophan can be achieved in only 2 h, on a cellulose HPTLC plate (89) these experiments will be described in detail in Section FV.C. 

Before synthetic chiral stationary phases were developed, attempts were made to use naturally occurring chiral materials for the stationary phase. Quartz, wool, lactose and starch were inadequate but triacetylated cellulose has met with some success. The synthetic stationary phases introduced by Pirkle are able to interact with solute enantiomers in three ways, one of which is stereochemically dependent. Typically these interactions are based on hydrogen bonding, charge transfer (rc-donoi -acceptor based) and steric repulsive types. An independent chiral stationary phase therefore consists of chiral molecules each with three sites of interaction bound to a silica (or other) support. Early work in this area demonstrated that 5-arginine bound to Sephadex would resolve 3,4-dihydroxy-phenylalanine, and that direct resolution of chiral helicenes could be accomplished with columns packed with 2-(2,4,5,7-tetranitro-9-fluorenylideneaminoxy)-propionamide or tri-P-naphthol-diphosphate amide. Amino acid esters have also been resolved with a silica bound chiral binaphthyl crown ether, but better separations are achieved with A-acylated amino acid derivatives with amino-acid derived chiral stationary phases. 

The primary use of cellulose film has been for wrapping purposes. The past years have witnessed a renewed interest in cellulose research and application sparked mostly by technological interests in renewable raw materials and more environmentally-friendly and sustainable recourses. It has been estimated that the yearly biomass production of cellulose is 1.5 tons, making it an inexhaustible source of raw material for environmentally-friendly and biocompatible products [3]. Cellulose derivatives are used for coatings, laminates, optical films, pharmaceuticals, food, and textiles. Numerous new applications of cellulose take advantage of its biocompatibility and chirality for the immobilization of proteins and antibodies and for the separation of enantiometric molecules, as well as the formation of cellulose composite with synthetic polymers and biopolymers. This chapter basically discussed on the medical applications of cellulose. 

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