Grafted linkers

In the chemical literature, linkers are further divided into integral linkers that are part of the resin and non-integral or grafted linkers, where a part of the linker is attached to the core of the resin. The integral linkers exhibit some disadvantages since the reaction takes place in direct proximity to the resin. Steric and electronic effects will exert a direct influence on the outcome of the reaction. An additional problem to be alleviated is the determination of the exact loading of a resin with an integrated linker [13]. 

Our library synthesis was carried out with a set of 27 tube-shaped solid phase synthesis support, called MicroTubes. These supports are prepared by radiation grafting of polystyrene ( — 350 pmol) onto polypropylene tubes, chemically functionalizing the polystyrene with aminomethyl groups to afford about 55 imol of amine per tube, inserting a reusable Rf ID tag into each tube, and heat-sealing the tube ends to prevent loss of the tag. The chemical conversion of all 36 aminomethyl tubes was carried out simultaneously using standard procedures with rink amide linker, each with —46 pmol of available amine per tube.1 2... 

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). 

In situ FC tests have shown that these membranes are capable of performances at least comparable to Nafion under fully humidified, 60°C operation conditions. Lifetimes were typically short however, with the introduction of DVB as a cross-linker during the graft copolymerization with styrene, lifetimes could be improved to around 1,000 hours. This could be further improved to over 6,(300 hours using a combination of DVB and triallyl cyanuarate as cross-linkers. ... 

The functionalization of silica with PPM and the subsequent immobilization of [Rh(COD)2]BF4 has been achieved by Pugin and Blaser [49]. The PPM ligand was immobilized by grafting the linker, 3-trimethoxysilylpropyl isocyanate, to the silica surface (the silicas used include Grace 332, Merck 100, Merck 60, Merck 40). The isocyanate moiety then reacts with the amine functionality of the PPM ligand to afford an amide linkage (35, Figure 5.17). Introduction of a solution of [Rh(COD)2]... 

In a subsequent paper, the authors developed another type of silica-supported dendritic chiral catalyst that was anticipated to suppress the background racemic reaction caused by the surface silanol groups, and to diminish the multiple interactions between chiral groups at the periphery of the dendrimer 91). The silica-supported chiral dendrimers were synthesized in four steps (1) grafting of an epoxide linker on a silica support, (2) immobilization of the nth generation PAMAM dendrimer, (3) introduction of a long alkyl spacer, and (4) introduction of chiral auxiliaries at the periphery of the dendrimer with (IR, 2R)-( + )-l-phenyl-propene oxide. Two families of dendritic chiral catalysts with different spacer lengths were prepared (nG-104 and nG-105). 

Expanding the variety and properties of linker groups increases the scope of practical applications of radiation-grafted polymer surfaces for the parallel synthesis of organic compounds. Linker molecules have a bearing on the types of reactions that can be performed and the ease of isolation of products after cleavage. 

Figure 2.4. Preparation of PEG-polystyrene graft supports [5,12,51,62,131]. Ar 4-(N02)C6H4 L linker X OH, NH2.

Amino group bearing derivatives of most other commonly used supports for solid-phase synthesis (PEG-grafted polystyrene, PEG, polyacrylamides, CPG) are commercially available these enable the irreversible attachment of different linkers. 

There have been a few reports of enzymatic cleavage of linkers for carboxylic acids from PEG-grafted polystyrene supports, such as Tentagel (Table 3.8). Some of these linkers are also sensitive towards acids or bases, and will, therefore, only remain uncleaved under a narrow range of reaction conditions. 

MIP films, applied to a QCM transducer, have been employed for chiral recognition of the R- and 5-propranolol enantiomers [107]. MIP films were prepared for that purpose by surface grafted photo-radical polymerization. First, a monolayer of 11-mercaptoundecanoic acid was self-assembled on a gold electrode of the quartz resonator. Then, a 2,2 -azobis(2-amidinopropane) hydrochloride initiator (AAPH), was attached to this monolayer. Subsequently, this surface-modified resonator was immersed in an ACN solution containing the MAA functional monomer, enantiomer template and trimethylolpropane trimethacrylate (TRIM) cross-linker. Next, the solution was irradiated with UV light for photopolymerization. The resulting MIP-coated resonator was used for enantioselective determination of the propranolol enantiomers under the batch [107] conditions and the FIA [107] conditions with an aqueous-ACN mixed solvent solution as the carrier. The MIP-QCM chemosensor was enantioselective to 5-propranolol at concentrations exceeding 0.38 mM [107]. 

In the mid to late 1990s, Mimotopes was producing rigid injection molded polypropylene devices that were surface grafted with either a hydrophilic copolymer of methacrylic acid/dimethyl acrylamide or the relatively hydrophobic polystyrene.12 The polymer was then suitably deriva-tized to allow the incorporation of a linker system. In contrast to the various commercial resins available at the time, the Crown was a macroscopic, quantized solid phase. As shown in Fig. 2, the Crowns were typically fitted to a polypropylene stem, which in turn could be fitted into a... 

Benzodiazepines were the first class of heterocyclic compounds to be synthesized on the SynPhase surface. In 1994, Ellman and co-workers24 reported a 192 member library of structurally diverse 1,4-benzodiazepines. These compounds were prepared on Mimotopes pins that were grafted with polyacrylic acid, the surface originally used for antibody epitope elucidation.10 Ellman and co-workers25 subsequently synthesized a 1680-member 1,4-benzodiazepine library on SynPhase Crowns that were grafted with a methacrylic acid/dimethylacrylamide copolymer, one of the first SynPhase surfaces designed for solid-phase synthesis. The synthesis was performed on a preformed linker-template system in order to avoid low aminobenzophenone incorporation in this case the HMP acid-labile linker... 

Polystyrene grafted SynPhase Lanterns were used by Makino et al.33 at Ajinomoto to synthesize a diverse quinazoline-2-thioxo-4-one library. Lanterns functionalized with long-chain HMP (hydroxymethylphenoxyvaleric amide) linker were coupled with nitrophenols by the action of DIC/ HOAt/DMAP to give nitrobenzenes 14 (Scheme 6). The nitro group was... 

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