Derivatized polysaccharides

Mourier s report was quickly followed by successful enantiomeric resolutions on stationary phases bearing other types of chiral selectors, including native and deriva-tized cyclodextrins and derivatized polysaccharides. Many chiral compounds of pharmaceutical interest have now been resolved by packed column SFC, including antimalarials, (3-blockers, and antivirals. A summary is provided in Table 12-2. Most of the applications have utilized modified CO, as the eluent. 

Starburst (TM) dendrimers with DTPA can contain 170 bound Gd(III) ions and have relaxivities (per bound Gd) up to 6 times that of Gd-DTPA (308). Both global and local motion contribute to the overall rotational correlation time. Attempts have been made to increase the re-laxivity of Gd(III) by optimizing the rotational correlation time via binding of Gd(III) to derivatized polysaccharides (309) and by binding lipophilic complexes to albumin in serum (310). The latter approach has achieved relaxivities as high as 44.2 mM l s1 for derivatized 72 (311). 

There are 22 chapters in the book and they cover the most important aspects of polymers as drugs, prodrugs, dmg delivery systems, and in situ prostheses. The major features promulgated are synthesis, derivatization, degradation, characterization, application, and evaluation techniques as well as new biodegradable materials, assemblies, hydrogels, telechelic polymers, derivatized polysaccharides, micro- and nanoparticles, mimetic... 

J. Sunamoto 110> reported a coating of the outer liposome leaflet with partially palmitoyl-derivatized polysaccharides according to route 2 in Fig. 53. These arti-... 

Modified-C02 mobile phases excel at stereochemical separations, more often than not outperforming traditional HPLC mobile phases. For the separation of diastereomers, silica, diol-bonded silica, graphitic carbon, and chiral stationary phases have all been successfully employed. For enantiomer separations, the derivatized polysaccharide, silica-based Chiralcel and Chiralpak chiral stationary phases (CSPs) have been most used, with many applications, particularly in pharmaceutical analysis, readily found in the recent literature (reviewed in Refs. 1 and 2). To a lesser extent, applications employing Pirkle brush-type, cyclodextrin and antibiotic CSPs have also been described. In addi-... 

Packed column SFC stationary phases are very similar or identical to those used for HPLC. With neat CO2 mobile phases, polymer or polymer-coated silica stationary phases have typically been used. With modified-C02 mobile phases, bonded-phase silica columns are typically used. For structural separations, diol, amino, or cyano stationary phases are most often used. For stereochemical separations, derivatized polysaccharide-bonded silica columns are most often the stationary phases of choice. A powerful feature of modified-C02 pSFC is the ability to serially connect different stationary phases to obtain enhanced or mul-... 

Fig. 18 Dependence of the net mobility of ANDS-derivatized polysaccharides on their molecular mass. Separation conditions were as for Fig. 17...

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. 

Related materials can be prepared in which the polysaccharides are linked to a silica support by covalently bound tether groups. For example, silica derivatized by 3-aminopropyl groups can be linked to polysaccharides using diisocyanates. These materials seem to adopt organized structural patterns on the surface, and this factor is believed to contribute to their resolving power. The precise structural basis of the chiral recognition and discrimination of derivatized polysaccharides has not been elucidated, but it appears that in addition to polar interactions, tt-tt stacking is important for aromatic compounds. ... 

Barnhart, W., Gahm, K, Hua, Z., Goetzinger, W. (2008) Supercritical fluid chromatography comparison of the poly(trans-l, 2-cydohexanediyl-bis-acrylamide) (P-CAP) column with several derivatized polysaccharide-based stationary phases./. Chromatogr. B, 875, 217-229. 

The importance of modified polysaccharides has been commented on briefly, and the uses of derivatized polysaccharides in the purification of biologically active molecules have been discussed. Polysaccharide derivatives used as affinity adsorbents and for immobilizing proteins have been prepared by the routes shown in Scheme 2. ... 

Binding acid groups to a polysaccharide (carb-oxymethyl, sulfate or phosphate groups) also results in increased solubihty and viscosity for reasons already outhned. Some derivatized polysaccharides, when moistened, have a pasty consistence. 

There are many classes of CSPs applicable in different mobile-phase modes. In particular, CSPs based on derivatized polysaccharides, native and derivatized cyclodextrins, macrocyclic glycopeptides, and Pirkle-type chiral selectors operate quite well in four separation modes, i.e RP, polar organic phase, NP, and super- or subcritical fluid chromatography (SFC) conditions. It is common that a chiral compound can be separated on the same CSP in more than one separation mode [58, 160, 166, 170-176]. For example, Nutlin-3, a small molecule antagonist of MDM2, has been baseline resolved from its enantiomer in all four mobile-phase conditions (Fig. 16) [170]. Multimodal enantioseparation on the same CSP would be greatly beneflcial for chiral method development in pharmaceutical industry. 

Derivatized polysaccharide CSPs are operational, quite well, in all three HPLC separation modes as well as under super- or sub-critical fluid conditions [153, 160, 166, 170, 176-178]. A previous study based on a collection of more than 100 pharmaceutically important compounds with diverse structures clearly showed that polysaccharide CSPs generally had much higher success rate in resolving enantiomers under normal-phase and SFC conditions, followed by RP and polar organic modes (Fig. 17) [167]. This study also revealed that amylose tris(3,5-dimethylphenylcarbamate) AD phase was more effective than the other studied polysaccharide CSPs in polar organic mode and SFC, whereas cellulose tris(3,5-dimethylphenylcarbamate) phase is more applicable in reversed-phase mode. This observation is consistent with two other studies [159, 160]. 

Harris R, JureUer SH, Kerschner JL, Trzasko PT, Humphreys RWR. 27 January 1999. Derivatized polysaccharides and preparation thereof in a densified fluid. European Patent Application EP893451 A2. 

Brush-type — acceptor and donator (e.g., derivatized polysaccharides)... 

The first diversely derivatized polysaccharide-based CSPs were introduced in chromatography by Okamoto and coworkers [44,47] in 1984. They prepared a series of tribenzoate and phenylcarbamate of cellulose. These derivatives were found to resolve a wide range of racemates having various functional groups. 

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