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Chemical Library Purification Strategies Based on Principles of Complementary Molecular Reactivity and Molecular Recognition

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journal contribution
posted on 28.05.1997 by Daniel L. Flynn, Joyce Z. Crich, Rajesh V. Devraj, Susan L. Hockerman, John J. Parlow, Michael S. South, Scott Woodard
A new methodology for solution-phase chemical library synthesis and purification is described. This approach applies fundamental properties of complementary molecular reactivity and recognition (CMR/R) as the basis for a general purification strategy. Specifically, parallel solution-phase reactions are purified by resins containing molecular recognition or molecular reactivity functionalities complementary to those of solution-phase reactants, reagents, and byproducts. When used in sequential or simultaneous combinations, various CMR/R resins remove excess reactants, reagents, and byproducts from solution-phase reaction products, which are isolated in purified form by filtration. Where reactions involve the need to remove byproducts or reagents that do not inherently contain sequestrable functionality, sequestration can be effected by the design and use of tagged reactants or reagents containing artificially-imparted molecular recognition functionality. An extension of this methodology utilizes CMR/R resins as the “quench phase” instead of a liquid-phase workup commonly used in other library purification strategies. Hence, the essential features of complementary molecular reactivity or molecular recognition required for reaction workup are expressed on resins. The CMR/R library purification strategy is general and highly amenable to automation. Examples are illustrated with amine acylations, the Moffatt oxidation, and the reaction of organometallics with carbonyl compounds.