MICROREACTOR /LIBRARY DESIGN FOR COMBINATORIAL DISCOVERY

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

Investigators

Linked publications & trials

Abstract

This proposal has three components, namely, new methodologies for assembling peptide libraries based on beta-amino acids, new strategies for assembling transient libraries for reactive metal complexes of these peptides, and the high-throughput screen of these libraries as catalysts for new asymmetric organic reactions with a novel and powerful microreactor system. The Research Plan will validate our schemes for constructing microreactor assays, generating ligand catalysts libraries, and integrating these technologies into a reaction discovery program. These investigations will provide new arrayed microreaction systems that will simplify and accelerate combinatorial synthesis effort. The new microreactor system will enable transient catalyst libraries to be generated in a high-throughput format and allow these complexes to be assayed as catalysts for a variety of asymmetry organic reactions. The new methodology for ligand and catalyst library generation and the capabilities provide by the new microreactor technology are integrated into a combinatorial approach for discovering new catalyst complexes and developing new asymmetric organ transformations. Integrating these basic investigations with the Core Facility will be essential for extending developments in the Research Plan to generally useful methodologies for library construction and combinatorial chemistry. The Research Plan will validate our schemes for constructing microreactor arrays, generating ligand and catalysts, and integrating these technologies into a reaction discovery program. However, the Core Facility will extend these technologies to constructing and evaluating the complete compound libraries. Without the Core Facility, efforts to generate the library sizes required for executing a valid catalyst and reaction discovery assay will be significantly retarded. Furthermore, the development and extension of technologies emerging from the Research Plan as generally useful methodologies in all fields of combinatorial chemistry and diversity-oriented discovery would be similarly delayed.