Convergent synthesis of complex diketopiperazines derived from pipecolic acid scaffolds and parallel screening against GPCR targets

Sivaraman Dandapani; Ping Lan; Aaron B. Beeler; Scott Beischel; Athier Abbas; Bryan L. Roth; John A. Porco; James S. Panek

doi:10.1021/jo061758p

Convergent synthesis of complex diketopiperazines derived from pipecolic acid scaffolds and parallel screening against GPCR targets

Sivaraman Dandapani, Ping Lan, Aaron B. Beeler, Scott Beischel, Athier Abbas, Bryan L. Roth, John A. Porco, James S. Panek

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

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).

Original language	English (US)
Pages (from-to)	8934-8945
Number of pages	12
Journal	Journal of Organic Chemistry
Volume	71
Issue number	23
DOIs	https://doi.org/10.1021/jo061758p
State	Published - Nov 10 2006
Externally published	Yes

ASJC Scopus subject areas

Organic Chemistry

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10.1021/jo061758p

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title = "Convergent synthesis of complex diketopiperazines derived from pipecolic acid scaffolds and parallel screening against GPCR targets",

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).",

author = "Sivaraman Dandapani and Ping Lan and Beeler, {Aaron B.} and Scott Beischel and Athier Abbas and Roth, {Bryan L.} and Porco, {John A.} and Panek, {James S.}",

year = "2006",

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volume = "71",

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T1 - Convergent synthesis of complex diketopiperazines derived from pipecolic acid scaffolds and parallel screening against GPCR targets

AU - Dandapani, Sivaraman

AU - Lan, Ping

AU - Beeler, Aaron B.

AU - Beischel, Scott

AU - Abbas, Athier

AU - Roth, Bryan L.

AU - Porco, John A.

AU - Panek, James S.

PY - 2006/11/10

Y1 - 2006/11/10

N2 - 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).

AB - 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).

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Convergent synthesis of complex diketopiperazines derived from pipecolic acid scaffolds and parallel screening against GPCR targets

Abstract

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