Synthesis of dihydropyridone scaffolds on solid support: Resin activation/capture approach/REACAP technology

✍ Scribed by Chixu Chen; Ian A. McDonald; Benito Munoz

• Publisher: Elsevier Science
• Year: 1998
• Tongue: French
• Weight: 211 KB
• Volume: 39
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(97)10529-9

✦ Synopsis

The importance of non-peptidic, combinatorial libraries to the discovery of new lead compounds with attractive biological and pharmacokinetic profiles has spurred a renaissance in the study of polymer supported covalent bond synthesis. 1 In order to fully develop libraries that are truly non-peptidic in nature, the repertoire of organic reactions that were once considered only possible in solution phase are being addressed within the context of the resin support environment. 2 Whereas recent efforts have been directed towards reductive amination chemistry, z cyclizations, 4 and, more importantly, organometallic approaches to carbon-carbon bond formation, 5'e'7 little attention has been given to the generation of reactive intermediates on solid support for subsequent elaboration to libraries of small, non-peptidic compounds.

A novel approach to the synthesis of compound libraries, which has been developed in our laboratory, is referred to as REsin Activation/Capture APproach or REACAP Technology. REACAP capitalizes on the formation and retention of a reactive intermediate on the resin which can be subsequently transformed into stable, covalently attached molecules. Any unreacted =reactive intermediate" is quenched and removed from the resin upon work-up, leaving only the desired products on resin (Figure ).