Convergent Synthesis of Complex Diketopiperazines Derived from Pipecolic Acid Scaffolds and Parallel Screening against GPCR Targets

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• 作者：Sivaraman Dandapani ; Ping Lan ; Aaron B. Beeler ; Scott Beischel ; Athier Abbas ; Bryan L. Roth ; John A. Porco ; Jr. ; James S. Panek
• 刊名：Journal of Organic Chemistry
• 出版年：2006
• 出版时间：November 10, 2006
• 年：2006
• 卷：71
• 期：23
• 页码：8934 - 8945
• 全文大小：665K
• 年卷期：v.71,no.23(November 10, 2006)
• ISSN：1520-6904

文摘

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A convergent approach to highly functionalized diketopiperazines (DKPs) using enantioenriched pipecolicacids is described. Scandium triflate-catalyzed [4 + 2] aza-annulation was employed to producestereochemically well-defined building blocks. A resin "catch and release" strategy was devised to convertannulation products to pipecolic acid monomers. Complex diketopiperazines were efficiently assembledutilizing one-pot cyclodimerization of pipecolic acids. Massively parallel screening of the complex DKPsagainst a panel of molecular targets identified novel ligands for a number of G-protein-coupled receptors(GPCRs).