Convergent synthesis of complex diketopiperazines derived from pipecolic acid scaffolds and parallel screening against GPCR targets.
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).
Dandapani
Sivaraman
S
Department of Chemistry and Center for Chemical Methodology and Library Development (CMLD-BU), Boston University, 590 Commonwealth Avenue, Boston, Massachusetts 02215, USA.
Lan
Ping
P
Beeler
Aaron B
AB
Beischel
Scott
S
Abbas
Athier
A
Roth
Bryan L
BL
Porco
John A
JA
Panek
James S
JS
D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D018360:Crystallography, X-Ray; D054659:Diketopiperazines; D004353:Drug Evaluation, Preclinical; D008958:Models, Molecular; D008968:Molecular Conformation; D010875:Pipecolic Acids / Q000737:chemistry*; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D001372:Aza Compounds; D054659:Diketopiperazines; D010875:Pipecolic Acids; D010879:Piperazines; D043562:Receptors, G-Protein-Coupled; C031345:pipecolic acid