Convergent synthesis of complex diketopiperazines derived from pipecolic acid scaffolds and parallel screening against GPCR targets
Convergent synthesis of complex diketopiperazines derived from pipecolic acid scaffolds and parallel screening against GPCR targets
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DOI：
10.1021/jo061758p
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发表时间：
2006-11-10
影响因子：
3.6
通讯作者：
Panek, James S.
中科院分区：
文献类型：
--
作者：
Dandapani, Sivaraman;Lan, Ping;Panek, James S.
描述了一种使用对映体富集的哌啶酸制备高度官能化的二酮哌嗪（DKP）的收敛方法。采用三氟甲磺酸钪催化的[4 + 2]氮杂环化来产生立体化学定义明确的结构单元。设计了树脂“捕获和释放”策略以将成环产物转化为哌啶酸单体。复杂的二酮哌嗪有效地组装利用一锅环二聚的哌啶酸。针对一组分子靶标对复合物DKP进行大规模平行筛选，鉴定了许多G蛋白偶联受体（GPCR）的新型配体。
A convergent approach to highly functionalized diketopiperazines (DKPs) using enantioenriched pipecolic acids is described. Scandium triflate-catalyzed [4 + 2] aza-annulation was employed to produce stereochemically well-defined building blocks. A resin "catch and release" strategy was devised to convert annulation products to pipecolic acid monomers. Complex diketopiperazines were efficiently assembled utilizing one-pot cyclodimerization of pipecolic acids. Massively parallel screening of the complex DKPs against a panel of molecular targets identified novel ligands for a number of G-protein-coupled receptors (GPCRs).