Abstract
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).
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Aza Compounds / chemical synthesis
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Aza Compounds / chemistry
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Catalysis
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Combinatorial Chemistry Techniques / methods*
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Crystallography, X-Ray
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Diketopiperazines
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Drug Evaluation, Preclinical
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Models, Molecular
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Molecular Conformation
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Pipecolic Acids / chemistry*
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Piperazines / chemical synthesis*
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Piperazines / chemistry
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Piperazines / pharmacology*
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Receptors, G-Protein-Coupled / antagonists & inhibitors*
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Aza Compounds
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Diketopiperazines
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Pipecolic Acids
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Piperazines
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Receptors, G-Protein-Coupled
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pipecolic acid