Merrifield resin grafting

A number of studies have recently been devoted to membrane applications [8, 100-102], Yoshikawa and co-workers developed an imprinting technique by casting membranes from a mixture of a Merrifield resin containing a grafted tetrapeptide and of linear co-polymers of acrylonitrile and styrene in the presence of amino acid derivatives as templates [103], The membranes were cast from a tetrahydrofuran (THF) solution and the template, usually N-protected d- or 1-tryptophan, removed by washing in more polar nonsolvents for the polymer (Fig. 6-17). Membrane applications using free amino acids revealed that only the imprinted membranes showed detectable permeation. Enantioselective electrodialysis with a maximum selectivity factor of ca. 7 could be reached, although this factor depended inversely on the flux rate [7]. Also, the transport mechanism in imprinted membranes is still poorly understood. 

A large variety of polymers has been considered. In the beginning, polystyrene and styrene/ divinylbenzene copolymers (Merrifield resins) were by far the most used.73 Then others were tested such as polyvinyls,47-50,61-64 polyacrylates,72 4,75 and cellulose.76,77 Most commonly, diphenylphos-phane groups were grafted on the polymeric support, either directly or via one CH2 group. 

FIGURE 5.10 Synthesis of a polyethyleneglycol-polystyrene graft polymer by etherification of Merrifield resin using potassium tetra(oxyethylene) oxide, followed by extension of the chain by reaction of the potassium salt, which is present as the crown ether.21 In several TentaGel resins, the connecting bond is an ethyl ether that is more acid-stable than the benzyl ether. 

Grafting on the resin was achieved via a nucleophilic substitution of the benzylic chlorine by the deprotonated OH-linker of 52 (Scheme 29) by using a mixture of KO Bu, 18-crown-6 and CsBr. Determining the nitrogen content of solid phase samples by elemental analyses was accomplished, to verify the functionalization of the polymer. This enables calculation of the degree of functionalization. Usually, an occupancy of more than 20 percent of the theoretical sites was achieved. Saponification of the functionalized Merrifield resin P-52 leads to the monoanionic NJ, 0 functionalized solid phase. Subsequent reaction with [ReBrtCOlsJ afforded the polymer mounted tricarbonyl rhenium complex P-52-Re (Scheme 29). 

Seven noncommercial acid-labile linkers have been reported recently in the literature and are shown in Figs. 1.8. (1.7-1.10) and 1.9 (1.11-1.13). The THP (tetrahy-dropyran) linker 1.7 (63), which is easily grafted onto Merrifield resin, has been used to support primary alcohols, secondary alcohols, hydroxylamines, and carboxylic acids. It is stable to strong nucleophiles and basic conditions and can be cleaved by... 

Other authors have described the use of the previously seen framework [39]. The grafting of the DIOP ligand (Eqs. 5-7) onto a Merrifield resin was performed by treatment of the insoluble aldehyde 21 with the (+)-diol 22 of the DIOP, leading to the ditosylate 23. This product was then treated with lithium diphenylphos-phide, affording the desired phosphinated resin 24, which contains 0.5 meq/g of phosphorus functions. The reaction with [RhCl(C2H4)2]2 gave an insoluble complex that may be used further in catalysis. 

Recently, Haag and coworkers reported on the synthesis of polystyrene beads dendronised with a hyperbranched polymer [66, 67]. The polystyrene-polyglycerol hybrid support 5 was obtained by grafting of a hyperbranched polyglycerol directly onto a Merrifield resin [67] or alternatively polymerising glycidol directly onto a polyhydroxylated crosslinked polystyrene... 

Polystyrene resin, frequently used resin material for solid-phase peptide synthesis (SPPS). The polymeric support for SPPS must be chemically inert, mechanically stable, completely insoluble in the solvents used, and easily separated by filtration. For many applications a copolymer of polystyrene with 1% of divinyl benzene as crosslinker is used. The dry resin beads are able to swell up to the five-or sixfold volume in the different organic solvents mainly used for peptide synthesis (e.g., dichloromethane or dimethylfor-mamide). For SPPS the resin material must be chemically functionalized in order to allow for attachment of a handle/liker (e.g. Wang resin), or the first amino acid (—> Merrifield resin). Hydrophilic tentacle polymers gels (TentaGel) are obtained by grafting polyethylene glycol (PEG) chains with an arbitrary degree of polymerization onto porous polystyrene beads. 

Even if Merrifield resins and their derivatives are still the most commonly used resins for the synthesis of small molecules, one of their limitations is the poor swelling in polar protic solvents. For instance, Merrifield resins can not be applied in protic solvents, such as water or alcohols. This problem, however, can be overcome by designing amphiphilic resins made of a 1% crosslinked polystyrene matrix onto which poly(ethylene oxide) chains are grafted (Fig. 3)... 

Scheme 12. TADDOL Precursors for Grafting (on Merrifield resin or on controlled-pore glass) and for Cross-Linking Suspension Copolymerization with Styrene. These TADDOL derivatives are prepared in the usual way from (suitably protected) components [21][78-81]. The zero- and first-generation Frechet-type [82] branches were attached by reaction of branch benzyl bromides with a TADDOL bearing four phenohc OH groups [22] [78] [79]. The cross-linked polymer beads we used had a diameter of ca. 400 pm. To keep the styryl derivatives from uncontroUed polymerization, they should be kept in the dark and in the cold.

Similar to the work by Frechet who grafted functional groups to heterogeneous polystyrene (see above), Hodges used living free-radical polymerization to prepare what he referred to as Rasta resin [23]. The Merrifield resin was first functionalized with reduced TEMPO to form a resin core. With the help of Rhodamine dye, it was confirmed that the grafts and associated functional groups were located... 

The cleavage of amino acid derivatives grafted to a Merrifield resin via an ester bonding occurs smoothly under sonication in the presence of sodium hydroxide and diverse ethanolamines. Complete hydrolysis without racemization is obtained in only 10 min, instead of many hours conventionally. 

Hodges et al. [152] and Bian and Cunningham [153] reported the grafting of PS, poly(acetoxystyrene), poly[styrene-b-(methyl methacrylate-co-styrene)], poly(acetoxystyrene-co-styrene), and poly(styrene-co-2-HEMA) copolymers onto 2,2,6,6-tetramethyl-l-piperidinyloxy nitroxide (TEMPO) bound Merrilield resin. Merrifield resin is a PS resin based on a copolymer of styrene and chloromethylstyrene cross-linked with divinylbenzene. In these works, a pronounced increase of particle size was observed, which was attributed to the formation of chains both at the surface and within the microspheres. The polymerization control was enhanced both on the surface and in solution by the addition of sacrificial nitroxide. 

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