Synthesis of diketopiperazines and skeletally diverse compounds using tetrahydropyridine scaffolds

ORGN 908

Sivaraman Dandapani, sivaram@bu.edu1, Ping Lan, Lan_P@wuchem.wustl.edu1, Aaron B. Beeler, beelera@chem.bu.edu1, Scott Beischel2, Athier Abbas2, Bryan R. Roth, bryan_roth@med.unc.edu3, John A. Porco Jr., porco@bu.edu1, and James S. Panek, panek@chem.bu.edu1. (1) Department of Chemistry and Center for Chemical Methodology and Library Development (CMLD-BU), Boston University, 24 Cummington Street, Boston, MA 02135, (2) National Institute of Mental Health Psychoactive Drug Screening Program and Department of Biochemistry, Case Western Reserve University Medical School, Case Western Reserve University Medical School, Cleveland, OH 44106, (3) National Institute of Mental Health Psychoactive Drug Screening Program and Department of Biochemistry, University of North Carolina at Chapel Hill, School of Medicine, Department of Pharmacology, 8032 Burnett-Womack, CB # 7365, Chapel Hill, NC 27599
Scandium triflate-catalyzed aza-annulation of chiral silanes provided efficient access to stereochemically well-defined tetrahydropyridines 1 and 2, which were converted to functionalized pipecolic acids. Homo- and hetero-dimerization of pipecolic acids provided complex diketopiperazines (DKP's) with considerable stereochemical variation. Massively parallel screening of the complex DKP's against a panel of molecular targets identified novel ligands for a number of G-protein-coupled receptors (GPCR's). In this presentation, we outline our efforts to produce complex DKP's as well as other skeletally diverse compounds from highly enantioenriched tetrahydropyridine scaffolds.

 

Combinatorial, Parallel, and Solid-Phase Chemistry
8:00 AM-12:00 PM, Thursday, 14 September 2006 Moscone Center -- Room 132, Oral

Division of Organic Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006