Efficient Synthesis of Optically Pure Nω-Alkylated l-Arginines

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.