Chiral phases celluloses

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. 

Other chiral phases include those based on proteins, cellulose triacetate, amino acids complexed with copper and chiral crown ethers. 

Chiral separations have become of significant importance because the optical isomer of an active component can be considered an impurity. Optical isomers can have potentially different therapeutic or toxicological activities. The pharmaceutical literature is trying to address the issues pertaining to these compounds (155). Frequendy separations can be accomplished by glc, hplc, or ce. For example, separation of R(+) and S(—) pindolol was accomplished on a reversed-phase cellulose-based chiral column with fluorescence emission (156). The limits of detection were 1.2 ng/mL of R(+) and 4.3 ng/mL of 5/—) pindolol in serum, and 21 and 76 ng/mL in urine, respectively. 

The requirements for homochirally pure a-amino acids have not ruled out any of these general synthetic methods (which all give racemic products), since resolution of DL-a-amino acids and their derivatives is a simple, albeit time-consuming, solution to this need. Classical methods for resolution include physical separation of the DL-amino acids themselves (by chromatography on a chiral phase e.g. resolution of DL-tryptophan over cellulose, see Section 4.15), fractional crystallisation of certain racemates or supersaturated solutions (through seeding with crystals of one enan-... 

Figure 10.7 compares the results of numerical calculations of the relaxation and of the parabolic models with experimental results [37]. The calculation parameters correspond to the case of the separation of the Troger s base enantiomers on microcrystalline cellulose triacetate, a chiral phase, using ethanol as the mobile phase [41]. 

Cellulose can be esterified with acetic anhydride to form acetylated paper with hydrophobic properties [12], These papers, which are commercially available from Schleicher and Schiill with 5-40% of acetyl residues, serve for the reversed-phase chromatography of lipophilic substances such as steroids (13). It has been suggested that these papers are suitable for separation of racemic mixtures due to the migration of optical antipodes at different rates on the chiral acetyl cellulose [14]. 

By using derivatives of cellulose 3,5-dimethylphenyl carbamate (Chiracel OD) as the chiral phase Bergman measured the enantiopurity of complexes of molybdenum (2.45) and iridium (2.46) (Figure 2.67). With the same type of stationary phase, Gladysz measured the ee of rhenium complexes ReCp(NO)P(C6H5)2Br (2.13), and uranyl-salophen complexes of uranium were analysed with a Chiracel ODH column. 

Liu, J. Stewart, J.T. High-performance liquid chromatographic analysis of ondansetron enantiomers in human serum using a reversed-phase cellulose-based chiral stationary phase and solid-phase extraction. J. Chromatogr. B Biomed. Sci. Appl. 1997, 694, 179-184. 

Enantiomers of phenyl-[ H5]phenylmethanol were separated by reversed-phase HPLC based on the isotopic chirality using cellulose tribenzoate-coated silica as a stationary phase and 2-propanol/hexane (5 95, v/v) mixture as a mobile phase. The stationary phase showed preferential retention of R)- — enantiomer with a separation factor of 1.008. Complete separation was achieved by a recycle column system after 65 cycles. 

As in GC, the uses of LC for the separation of chiral species have significantly increased. Column materials now include chiral phases that may, for example, be based on monolithic silica columns with chemically bonded beta-cyclodextrin, teicoplanin, or cellulose tris(3,5-dimethylphenylcarbamate). Hydro-phobic amino compounds have been separated by LC using a crown ether dynamically coated chiral stationary phase. 

It is worth mentioning that natural products, due to their enantiopurity, play an important technical function in the development of suitable methods for chiral separations. Cellulose and amylose, which are easily accessible chiral polymers, after derivatization, are used as chiral stationary phases for both HPLC and TLC [29-31]. Microbial degradation of starch yielded CDs, -CD-bonded silica gel provide the most popular chiral stationary phases. 

Chiral stationary phases in tic have been primarily limited to phases based on normal or microcrystalline cellulose (44,45), triacetylceUulose sorbents or siHca-based sorbents that have been chemically modified (46) or physically coated to incorporate chiral selectors such as amino acids (47,48) or macrocyclic antibiotics (49) into the stationary phase. 

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. 

Many cellulose derivatives form Hquid crystalline phases, both in solution (lyotropic mesophases) and in the melt (thermotropic mesophases). The first report (96) showed that aqueous solutions of 30% hydroxypropylceUulose [9004-64-2] (HPC) form lyotropic mesophases that display iridescent colors characteristic of the chiral nematic (cholesteric) state. The field has grown rapidly and has been reviewed from different perspectives (97—101). 

The potential for use of chiral natural materials such as cellulose for separation of enantiomers has long been recognized, but development of efficient materials occurred relatively recently. Several acylated derivatives of cellulose are effective chiral stationary phases. Benzoate esters and aryl carbamates are particularly useful. These materials are commercially available on a silica support and imder the trademark Chiralcel. Figure 2.4 shows the resolution of y-phenyl-y-butyrolactone with the use of acetylated cellulose as the adsorbent material. 

The second system studied was the separation of the chiral epoxide enantiomers (la,2,7,7a-tetrahydro-3-methoxynaphth-(2,3b)-oxirane Sandoz Pharma) used as an intermediate in the enantioselective synthesis of optically active drugs. The SMB has been used to carry out this chiral separation [27, 34, 35]. The separation can be performed using microcrystalline cellulose triacetate as stationary phase with an average particle diameter greater than 45 )tm. The eluent used was pure methanol. A... 

The competitive adsorption isotherms were determined experimentally for the separation of chiral epoxide enantiomers at 25 °C by the adsorption-desorption method [37]. A mass balance allows the knowledge of the concentration of each component retained in the particle, q, in equilibrium with the feed concentration, < In fact includes both the adsorbed phase concentration and the concentration in the fluid inside pores. This overall retained concentration is used to be consistent with the models presented for the SMB simulations based on homogeneous particles. The bed porosity was taken as = 0.4 since the total porosity was measured as Ej = 0.67 and the particle porosity of microcrystalline cellulose triacetate is p = 0.45 [38]. This procedure provides one point of the adsorption isotherm for each component (Cp q. The determination of the complete isotherm will require a set of experiments using different feed concentrations. To support the measured isotherms, a dynamic method of frontal chromatography is implemented based on the analysis of the response curves to a step change in feed concentration (adsorption) followed by the desorption of the column with pure eluent. It is well known that often the selectivity factor decreases with the increase of the concentration of chiral species and therefore the linear -i- Langmuir competitive isotherm was used ... 

A precursor in the synthesis of a promising calcium sensitizing agent from E. Merck [33], a chiral thiadiazin-2-one EMD 53986, 3,6-Dihydro-5-[l,2,3,4-tetrahy-dro-6-quinolyl]-6-methyl-2H-l,3,4-thiadiazin-2-one [26]. The study was performed using Celluspher , a CSP prepared from cellulose tri(p-methylbenzoate) according to a patent from Ciba-Geigy [34]. The spherical particles had a mean particle diameter of 20 3 pm and the mobile phase was pure methanol. 

The reagent can be used, for example, on silica gel, kieselguhr and Si 50000 layers as well as on aluminium oxide, cellulose or chiral layers. Neither do difficulties occur on RP 18, Diol, NHj and CN phases. Silver nitrate- [4] and calcium oxalate-impregnated layers [9] are also suitable. However, polyamide phases are colored yellow. 

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