Synthesis parallel array

Parallel array synthesis was used to access the 3-aryl-tetrahydro-l,2-diazepines 90 (and other related compounds) by cyclisation of the chloro ketones 88 on reaction with hydrazine to give 89 followed by sulfonamide formation the Si-TrisAmine was added at the end as a scavenger to remove any unreacted arylsulfonyl chloride remaining <06MCL3777>. 

Polymer-assisted methodology has been used several times for parallel-array synthesis of libraries involving three to five synthetic steps. Scheme 11 shows a three-step solution-phase synthesis of 2-thioxo-4-dihydro-pyrimid-inones wherein the key purification step involved amine resin 1 to sequester excess aldehydes and isot,hiocyanates from upstream transformations. Thermal cyclization of the purified intermediates gave the desired 2-thioxo-4-dihydropyrimidinones in excellent yields and purities.83... 

Combinatorial chemistry is a sophisticated set of techniques used to synthesize, pnrify, analyze, and screen large numbers of chemical compounds, far faster and cheaper than was previously possible. The direct precursor of combinatorial chemistry was the solid-phase synthesis of polypeptides developed by American biochemist Robert Bruce Merrifield in the 1960s, followed by the advances in laboratory automation since then. Initial development of the field has been led by the pharmaceutical industry in the search for new drugs, but its applications are spreading into other fields of chemistry. Other terms associated with this field are parallel array synthesis and high-throughput chemistry. 

Figure 14.1 The conceptual difference between the synthesis of a combinatorial library with exponential increase in number of compounds and the synthesis of parallel arrays of discrete compounds.

The application of multiple reaction parameters executed in a parallel array format has been used to expedite the identification of optimal conditions for the synthesis of a collection of almost 600 new interleukin-1/ converting enzyme inhibitors [89]. The reaction in question was the problematic conversion of a / -tert-butyl aspartic acid bromoethylketone to the corresponding acyloxyketone (Scheme 2.63). The study en-... 

One form of combinatorial chemistry involves parallel synthesis or array synthesis. In parallel synthesis, each new compound is formed in its own miniature reactor or well. If a new library is to contain 500 members, synthesis of the library will require 500 wells in the final step. For this reason, parallel synthesis is associated with the phrase one compound-one well. 

Adler, F., Turk, G., Frank, R., et al. (2000) A new array format for the automated parallel combinatorial synthesis by the SPOT-technique. In Innovation and Perspectives in Solid Phase Synthesis (Epton, R., ed.), Mayflower Worldwide, Kings-winford, UK, pp. 221-222. 

Array synthesis The form of parallel synthesis in which the reaction vessels are maimained in a particular spatial arrange-mem, such as a grid in a microtiter plate. Such arrays genentted on a microscopic basis arc termed a sitatially addresstdtk library. 

Matysiak S, Reuthner F, Hoheisel J D (2001). Automating parallel peptide synthesis for the production of PNA library arrays. Biotechniques. 31 896-904. 

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