Boronic immobilization

Compounds 167-171 outlined in Fig. 43 form another series of diboronic acids that form complexes with mono- and disaccharides. In these cases the asymmetrical immobilization of chromophoric functional groups, e.g., aromatic rings in 167-170 or Fe -complexation with the related boronate 171, can be analyzed by circular dichroism measurements [256-262]. 

Crude chloroform-methanol-water (30 60 8, v/v) extracts of immunostainedTLC bands were analyzed without further purification by nanoelectrospray low-energy mass spectrometry. The authors showed that this effective PLC/MS-joined procedure offers a wide range of applications for any carbohydrate-binding agents such as bacterial toxins, plant lectins, and others. Phenyl-boronic acid (PBA) immobilized on stationary support phases can be put to similar applications. This technology, named boronate affinity chromatography (BAC), consists of a chemical reaction of 1,2- and 1,3-diols with the bonded-phase PBA to form a stable... 

Bergseid et al. (2000) also reported on the use of SHA-activated chromatography supports for the coupling of boronate-containing affinity ligands. In this case, immobilized RNase A was used to purify anti-RNase antibodies from antiserum samples. RNase A was modified with an NHS-PDBA crosslinker at a molar ratio of 100 1 (crosslinkenprotein), purified to remove excess crosslinker, and then coupled to an SHA-agarose support in 0.1 M sodium bicarbonate, pH 8.0. 

Stolowitz, M.L., Ahlem, C., Hughes, K.A., Kaiser, R.J., Kesicki, E.A., Li, G., Lund, K.P., Torkelson, S.M., and Wiley, J.P. (2001) Phenylboronic acid-salicylhydroxamic acid bioconjugates. 1. A novel boronic acid complex for protein immobilization. Bioconjugate Chem. 12, 229-239. 

Y. Li, J. Ding, M. Day, Y. Tao, J. Lu, and M. D iorio, Novel stable blue-light-emitting oligofluorene networks immobilized by boronic acid anhydride linkages, Chem. Mater., 15 4936-4943, 2003. 

The palladium-catalyzed coupling of boronic acids with aryl and alkenyl halides, the Suzuki reaction, is one of the most efficient C-C cross-coupling processes used in reactions on polymeric supports. These coupling reactions requires only gentle heating to 60-80 °C and the boronic acids used are nontoxic and stable towards air and water. The mild reaction conditions have made this reaction a powerful and widely used tool in the organic synthesis. When the Suzuki reaction is transferred to a solid support, the boronic add can be immobilized or used as a liquid reactant Carboni and Carreaux recently reported the preparation of the macroporous support that can be employed to efficiently immobilize and transform functionalized arylboronic adds (Scheme 3.12) [107, 246, 247]. 

Evaluation of this support for organic chemistry included peptide chemistry (synthesis of Fmoc-Val-Phe-Ala-OH) and a Suzuki coupling of immobilized 4-iodoben-zoic acid with 4-methylbenzene boronic acid coupled under standard conditions. 

Recently, Hebei and Haag reported on the immobilization of aryl boronic acids (62) on a dendritic polyglycerol support (15) (Fig. 7.8, M =8000 g mol ) (Scheme 7.10) [57]. This commercially available support was directly used and no additional... 

Oxindoles are prepared using a solid-phase Pummerer reaction. Thus, the immobilized amide 182 undergoes the Pummerer rearrangement on treatment with TFAA and boron trifluoride diethyl etherate (BF3 Et20) (Equation 118). Cleavage of the oxindole from the linker is achieved using samarium iodide and 1,3-dimethyl-3,4,5,6-tetrahydro-2(lH)-pyrimidinone (DMPU) <2003CC2380>. 

In a similar way, Guiles and co-workers immobilized an aryl pinacol boronate on resin via an ester linkage, and then a small number of aryl halides were coupled to this (Scheme 31). The products were cleaved and immediately transformed into their methyl esters, presumably for ease of analysis and separation from unreacted boronate. The reaction was found to be slower than that of the opposite polarity (i.e., with the resin-bound iodide), and only moderate yields were obtained after as much as 48 h. Yields could be considerably improved upon a second round of coupling, but only one example was given of this. The aryl bromides were found to react only upon heating. 

An interesting polymer-assisted variant of the Suzuki-reaction was recently disclosed by Vaultier and coworkers (Scheme 17) [43]. Aryl boronic acids can be immobilized on an ion exchange resin. Under Suzuki-Miyaura coupling conditions bisaryl species are released into solution and isolated with minimum purification. The authors also demonstrated that this strategy can be employed for the synthesis of macroheterocycles. 

Specific applications have been described for the separation of immunoglobulins.174 The ligand used and immobilized on a solid phase carriers was m- or p-aminophenyl boronic acid. Antibodies were adsorbed from feed... 

Phase-switching strategy was applied to the multistep synthesis of isoxazolines 45-47. The approach exploits the boronic acid functionality as a phase-tag which can be easily immobilized on diethanolaminomethyl polystyrene (DEAM-PS) resin and then released by treatment with wet THF. Each reaction step was carried out in solution and the products were purified by addition of the scavenging resin, followed by filtration, washing of the supported material, hydrolytic release and evaporation. Finally, the boronic acid could be used to introduce additional substituents on the molecule. For example, 46 was converted into the biaryl-containing isoxazoline 47 by a Suzuki cross-coupling reaction <07JCO193>. 

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