Poly -based supports

The important action of electrostatic forces between a cationic model and an anionic polynucleotide is clearly shown in Fig. 7. The hypochromicity sharply decreased with the ionic strength of the solution, which indicates that the base-base interactions between A12 and Poly U supported by the electrostatic attractive forces are weakened by the shielding effects of added salts. 

A variety of reactions have been conducted. Catalysts based on noble metals on Deloxan amino poly siloxane supports have been used. Hitzler et al. (1998) have reported alkylation of mesitylene with propylene or wopropanol in SC propylene or CO2 using a solid acid Deloxan catalyst. Pesiri et al. (1998) have carried out selective epoxidation in SC CO2 with transition metal catalysts (V, Ti, Mo) and tert-BHPO high conversion and selectivity have been reported. 

Chemical composition of packings. Today, a wider variety of different support materials is available from which to choose. Silica is still widely used, though preparative grades often possess a relatively wide particle size distribution as compared to polymer-based supports. One serious limitation of silica-based supports is the low stability of silicas to alkaline pH conditions, which limits use of caustic solutions in sanitization and depyrogenation. Polymer-based supports, which include poly(styrene-divi-nyl benzene)- or methacrylate-based materials, are widely available and have gained increased acceptance and use. Nonfunctionalized poly(styrene-divinyl... 

Scheme 19 The poly(4-vinylpyridine)-based supports PVP- % and PVPN-n%/MTO, and the polystyrene-based supports PS- %/MTO, where n is the cross-linkage percentage with divinylbenzene...

The first system is based on a poly (norbornene)-supported Co salen and the second system is based on a poly(styrene) backbone. For the poly (norbornene) system, a homopolymers and several different copolymers were prepared (44), with varying fractions of Co salen side-chains and spacer side-chains (Figure 3, copolymer la-c and homopolymer Id). For the poly (styrene) system, both homopolymers of salen-containing monomers and copolymers with styrene (45,46) were prepared (Figure 3, copolymer 2a-c and homopolymer 2d). 

Finally, libraries aimed to chiral resolution of racemates will be covered here in particular, the use of chiral stationary phases (CSPs) has recently been reported for the identification of materials to be used for chiral separation of racemates by HPLC. The group of Frechet reported the selection of two macroporous poly methacrylate-supported 4-aryl-1,4-dihydropyrimidines (DHPs) as CSPs for the separation of amino acid, anti-inflammatory drugs, and DHP racemates from an 140-member discrete DHP library (214,215) as well as a deconvolutive approach for the identification of the best selector phase from a 36-member pool library of macroporous polymethacrylate-grafted amino acid anilides (216,217). Welch and co-workers (218,219) reported the selection of the best CSP for the separation of a racemic amino acid amide from a 50-member discrete dipeptide iV-3,5-dinitrobenzoyl amide hbrary and the follow-up, focused 71-member library (220). Wang and Li (221) reported the synthesis and the Circular Dichroism- (CD) based screening of a 16-member library of CSPs for the HPLC resolution of a leucine ester. Welch et al. recentiy reviewed the field of combinatorial libraries for the discovery of novel CSPs (222). Dyer et al. (223) reported an automated synthetic and screening procedure based on Differential Scanning Calorimetry (DSC) for the selection of chiral diastereomeric salts to resolve racemic mixtures by crystallization. Clark Still rejxrrted another example which is discussed in detail in Section 9.5.4. 

Current practice of the conventional solid phase peptide synthesis (the Merrifield method) is based largely on the use of polystyrene and poly-dimethylacrylamide supports (see Fig. 17). The latter polymer was introduced in the 1970s [12,133 to provide a relatively more polar support, as compared with polystyrene. However, accumulation of experimental evidoice since then (ct Rrf. 70), indicates that an ideal polyn r support for SPPS should be comi tible with both polar (H-bonding) and nonpolar (hydrophobic) residues on the peptic grafts (Fig. 17). When the polymer support is not compatible with the growing peptide grafts, phase separation occurs, and the synthesis becomes inefficient or impracticable. 

In a different approach based on membrane technology, oligomerization of ethene has also been examined using a poly(ethersulfone)-supported ionic liquid membrane containing [EMIMjCl-AlCh ionic liquids with or without the presence of [NiCl2 P(cyclohexyl)3]2 dimerization catalyst and dichloroethylaluminate as an acid scavenging co-catalyst [107]. 

Many different support materials were developed [3, 4] since the original use by Merrifield of a polystyrene-based support material for polypeptide synthesis [5]. The work of Merrifield is described in Chap. 8 (see section on proteins). Beads of copolymers of styrene with divinyl benzene are available commercially and have been widely used as supports for many reactions. Many other polymeric materials are also used. These can be various other type of copolymers of styrene or with other polymers. The list includes cellulose, starch, polyalkanes, polyamides, poly(glycidyl methacrylate), polyisobutylene, polynorbomene, polyacrylamide, and others. In some instances, even glass was used. The more prominent support materials are presented below. 

Polyamide supports such as poly-L-lysine (MW 80,000) (Chapman and Kleid, 1973), polydimethylacrylamide (Gait and Sheppard, 1976, 1977), and polyacrylmorpholide (Narang r u/., 1977) have been reported for the synthesis of oligonucleotides. Polyamide resins, being more polar, are claimed to be more compatible with oligonucleotide synthesis than are their styrene-based counterparts. Polypeptide synthesis has also been reported on a polydimethylacrylamide-based support (Atherton et al., 1975). 

The choice of polymer support is the most crucial factor in solid-phase oligonucleotide synthesis. Various types of supports used by different workers are summarized in Tables 5-1 and 5-2. Although most reported uses of polymers in nucleotide syntheses are styrene-based supports (both insoluble and soluble), other polymers such as polyamides, poly(ethyIene glycol), vinylacetate-V-vinylpyrrolidone copolymer, poly(vinyl alcohol), Sephadex LH20, and silica gel have also been used. 

Several of the polystyrene-based supports aim at increasing the size of the spacer-arm, thus making the attached peptide more easily accessible to the reagents. For example, several modified supports using a modified macroreticular polystyrene as a base have been reported (Inman et al., 1977). Amino groups for peptide attachment were located at the end of poly(ethylene glycol) units that were directly attached to the polystyrene core. 

Garcia-Martin F, Quintanar-Audelo M, Garcia-Ramos Y, Cruz LJ, Gravel C, Furic R, Cruz S, Tulla-Puche J, Albericio F (2006) ChemMattix, a poly(ethylene glycol)-based support for the solid-phase synthesis of complex peptides. J Comb Chem 8 213-220... 

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