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Synthesis 2008(15): 2391-2397  
DOI: 10.1055/s-2008-1067165
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Efficient Synthesis of Optically Pure Nω-Alkylated l-Arginines

Dennis Schade, Jürke Kotthaus, Bernd Clement*
Department of Pharmaceutical and Medicinal Chemistry, Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Gutenbergstraße 76, 24118 Kiel, Germany
Fax: +49(431)8801352; e-Mail: bclement@pharmazie.uni-kiel.de;
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Publication History

Received 26 February 2008
Publication Date:
08 July 2008 (online)

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Abstract

A number of Nω-substituted l-arginines have been described to date, particularly with regard to nitric oxide synthase (NOS) modulators. Elaborate multistep syntheses and low yields limit the scope of preparing these modified l-arginines. We describe a synthetic methodology that delivers Nω-alkylated l-arginine derivatives from protected l-ornithine in a three-step sequence with excellent overall yields (81-90%) and in high purity. Analysis of the synthesized amino acids on a Crownpak Cr(+) column revealed no significant racemization, that is, >99.9% ee for all final compounds.

Key words

nitric oxide - N ω-alkyl - l-arginine - NOS - DDAH

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