Chiralcel structure

Starting from a collection of samples remarkably well resolved (alpha > 6) on Chiralcel OD (Cellulose tris(3,5-dimethylphenylcarbamate) coated on aminopropyl silica), a putative three-point enantiophore for binding to CSR was derived (Fig. 4-10). This enantiophore query was used to search (CFS 3D search) within a list comprising 4203 compounds tested on Chiralcel OD. From this search domain of CHIRBASE 3D, 191 structures were found to match the enantiophore. 

In order to enhance our ligand-based query hypothesis, the structural fragments of the initial query were generalized but linked with the same distance constraints. A search of this final query (see Fig. 4-10) in the same list yielded 690 hits and a statistically significant correlation of the presence of this enantiophore and the enan-tioselectivity of the compounds was found (94 % of those are well resolved on Chi-ralcel OD). Note that out of the 4203 compounds of the Chiralcel OD domain search, a 2D search found 1900 structures that contain the substructural features of the generalized query. 

Fig. 4-11. Examples of structure fitting the generalized Chiralcel OD ligand-based query.

A quick inspection of similarity maps in Fig. 4-14, allows one to see at once that Chiralcel OD and Whelk-0 1 molecule sets contain notable structural differences, whereas AGP and OVM data sets contain much more structurally related molecules. 

The purpose of this study is only intended to illustrate and evaluate the decision tree approach for CSP prediction using as attributes the 166 molecular keys publicly available in ISIS. This assay was carried out a CHIRBASE file of 3000 molecular structures corresponding to a list of samples resolved with an a value superior to 1.8. For each solute, we have picked in CHIRBASE the traded CSP providing the highest enantioselectivity. This procedure leads to a total selection of 18 CSPs commercially available under the following names Chiralpak AD [28], Chiral-AGP [40], Chiralpak AS [28], Resolvosil BSA-7 [41], Chiral-CBH [40], CTA-I (microcrystalline cellulose triacetate) [42], Chirobiotic T [43], Crownpak CR(-i-) [28], Cyclobond I [43], DNB-Leucine covalent [29], DNB-Phenylglycine covalent [29], Chiralcel OB [28], Chiralcel OD [28], Chiralcel OJ [28], Chiralpak OT(-i-) [28], Ultron-ES-OVM [44], Whelk-0 1 [29], (/ ,/ )-(3-Gem 1 [29]. 

Figure 3.1 Chemical structures of the current most successfully employed derivatised polysaccharide CSPs. (a) CHIRALPAK AD Amylose tris (3,5-dimethylphenylcarbamate) coated onto a silica support, (b) CHIRALPAK AS Amylose tris [(S)-a-methylbenzylcarbamate] coated onto a silica support, (c) CHIRALCEL OD Cellulose tris (3,5-dimethylphenylcarbamate) coated onto a silica support, (d) CHIRALCEL OJ Cellulose tris (4-methylbenzoate) coated onto a silica support.

FIGURE 10 Chromatograms of enantiomeric resolution on cellulose tribenzoate CSPs. (a) ( )-//ireo-Methylphenidate on Chiralcel OB CSP, with hexane-ethanol-methanol-trifluoroacetic acid (480 9.75 9.75 0.5, v/v/v/v) as the mobile phase containing 0.2 mM benzoic acid, (b) ( H/ireo-methylphenidate on Chiralcel OB CSP, with hexane-ethanol-methanol-trifluoroacetic acid (480 9.75 9.75 0.5, v/v/v/v) as the mobile phase containing 0.2 mM phenol, (c) Ic aromatase inhibitor on Chiralcel OJ-R CSP, with acetonitrile-water (50 50, v/v) as the mobile phase, (d) lie aromatase inhibitor on Chiralcel OJ-R CSP, with acetonitrile-water (50 50, v/v) as the mobile phase. For structures of Ic and lie aromatase inhibitors, see later (Fig. 18). (From Refs. 98, 100.)... 

Cabovska Plasma 0.2 Risperidone, R068808 (structural LLE (MTBE) Chiralcel OJ column 10 mM ammonium ESI, positive mode, Matrix effects, [53]... 

One important type of chiral packing material is derivatized polysaccharides, which provide a chiral lattice, but separation is improved by the addition of structural features that enhance selectivity. One group of compounds includes aroyl esters and carbamates, which are called Chiralcels (also spelled Chiracel) two of the most important examples are the 4-methylbenzoyl ester, called Chiralcel OJ, and the 3,5-dimethylphenyl carbamate, called Chiralcel OD. There is a related series of materials derived from amylose rather than cellulose, which have the trade name Chiralpak. 

Figure 10.9. Separation of racemic drugs belonging to different structural types on series coupled Chiralpak AD, Chiralcel OD and Chirex 3022 columns with carbon dioxide-methanol (containing 0.5% triethylamine and 0.5% trifluoroacetic acid) as mobile phase using composition programming. Peaks 1 = ibuprofen 2 = fenoprofen 3 = clenbuterol 4 = propranolol and 5 = lorazepam. (From Ref. [122] Preston Publications).

Many researchers have documented the effect of the mobile phase on the enantioselectivity of different racemates on polysaccharide-based CSPs. However, up to the present time, no comprehensive study aimed at identifying the association between the stmctural features present on solute and appropriate mobile phase conditions has yet been proposed. Piras et al. [33] have studied the characteristic features of about 2363 racemic molecules separated on a Chiralcel OD CSP. The mobile phase used for these racemates was compared with their structures, which are available from CHIRBASE (http //www.chirbase.u-3mrs.fr/chirbase/). The data setup was submitted to data-mining programs for molecular pattern recognition and mobile phase predictions for new cases. Some of the substmctural... 

Polysaccharide derived CSPs are among the most used for HPLC enantiosepara-tion due to their broad application domain, either in normal [66] or reversed-phase [52, 67] conditions, and their high loadability [66], These features make them CSPs of first choice for LC and CCC preparative purposes. The first application of polysaccharide derivatives to CCC was reported in 2006 [38]. Cellulose and amy-lose 3,5-dimethylphenylcarbamates, the CS contained in the well-know Chiralcel OD and Chiralpak(S) AD CSPs, were used. Although solubility of these CSs limits the use of coated polysaccharide-derivatives-containing CSPs in HPLC, their macromolecular structure prevents the formation of real solutions with solvents. Instead, these compounds swell and originate colloid solutions or suspensions of enough stability to be used in CCC. 

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