Polymer-supported Library Synthesis

Microwave-assisted Polymer-supported Library Synthesis 

Microwave-assisted Soivent-free Library Synthesis 

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Microwave-assisted Polymer-supported Library Synthesis... 

Combinatorial chemistry Library Microarray Solid-phase synthesis Automated synthesis Polymer-supported solution synthesis Tag-assisted solution synthesis High-throughput synthesis... 

These conceptual goals are attained by several combinatorial methods and tools. Characteristic for combinatorial chemistry is the synthesis on solid support or by polymer-supported synthesis, allowing for much higher efficiency in library production. Synthesis can be conducted either in automated parallel synthesis or by split-and-recombine synthesis. Centerpieces of combinatorial methods further include specific analytical methods for combinatorial... 

As for the solid support, several polymer-supported amines were tested (Fig. 2). For either the pyrazole and isoxazole synthesis, the best results were given by aniline-functionalized cellulose, which has also the advantage of a relatively low cost. For the 2-aminopyrimidine library, polystyrene-based piperazine and piperidine gave products with a much higher purity compared with other secondary non-cyclic or primary amines, hi both cases, the resins could be reused for up to four times before degradation in their behavior was observed. This reusability could be further enhanced (up to 10 cycles for cellulose-based aniline) when the microwave-assisted protocols were used. 

Kobayashi, S. Combinatorial Library Synthesis Using Polymer-supported Catalysts. In Combinatorial Chemistry, Fenniri, H., Ed., Oxford University Press Oxford, U.K., 2000 pp 421-432. 

In 2001, Sarko and coworkers disclosed the synthesis of an 800-membered solution-phase library of substituted prolines based on multicomponent chemistry (Scheme 6.187) [349]. The process involved microwave irradiation of an a-amino ester with 1.1 equivalents of an aldehyde in 1,2-dichloroethane or N,N-dimethyl-formamide at 180 °C for 2 min. After cooling, 0.8 equivalents of a maleimide dipo-larophile was added to the solution of the imine, and the mixture was subjected to microwave irradiation at 180 °C for a further 5 min. This produced the desired products in good yields and purities, as determined by HPLC, after scavenging excess aldehyde with polymer-supported sulfonylhydrazide resin. Analysis of each compound by LC-MS verified its purity and identity, thus indicating that a high quality library had been produced. 

Polymer-bound 1-hydroxybenzotriazole 1008 reacts with carboxylic acids in the presence of 1,3-diisopropylcarbo-diimide (1,3-DIC) and DMAP to produce esters 1009. Treated with hydroxylamine, esters 1009 are converted to hydroxamic acids 1010 (Scheme 167) <20030BC850>. Starting 1-hydroxybenzotriazole 1008 is recycled in the process and can be used for other syntheses. This method is well suited for automated synthesis of a library of hydroxamic acids. In similar applications of polymer-supported 1-hydroxybenzotriazole 1008, a wide variety of amides is synthesized <1997JOC2594, 2002JC0576>. 

Ley S V, Baxendale IR, Myers RM (2006) The use of polymer supported reagents and scavengers in the synthesis of natural products. In Boldi AM (ed) Combinatorial synthesis of natural product-based libraries. CRC Press Boca-Raton, pp 131-163... 

The simplicity of these transformations and high yields in both steps indicate that the preparation of compounds of type 106 from 1, 2 can easily be automated and performed as liquid phase parallel synthesis. The starting materials 1,2 can also be put on a polymer support to obtain combinatorial libraries of l,l -di-, l,r,2 -tri-, l,l, 2, 2 -tetra-, l,r,2, 3 -tetra-, l,r,2, 2, 3 -penta- and... 

Oikawa M, Ikoma M, Sasaki M (2005) Parallel synthesis of tandem Ugi/Diels-Alder reaction products on a soluble polymer support directed toward split-pool realization of a small molecule library. Tetrahedron Lett 46 415-418... 

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