Synthesis of 2-(nitromethyl)ornithine from ornithine mediated by cobalt(III).

Abstract

Rac.-p-(tris(2-aminoethyl)amine-2-(nitromethyl)ornithine)cobalt(III) trichloride (2d) was obtained by a simple three-step procedure from ornithine using cobalt template chemistry. p-(Tris(2-aminoethyl)amine-ornithine)cobalt(III) trichloride (2a) was obtained from tris(2-aminoethyl)amine (tren) and (S)-ornithine in the presence of cobalt(II), which was oxidised to cobalt(III) during the reaction. Complex 2a was selectively oxidised with thionyl chloride-dimethyl formamide to p-(tris(2-aminoethyl)amine-dehydro-ornithine)cobalt(III) trichloride 2b. Complex 2c, in which reaction of thionyl chloride-dimethyl formamide has also occurred at the δ-amine of ornithine, was obtained at longer reaction times. Complex 2b reacted with nitromethane anion to give rac.-p-(tris(2-aminoethyl)amino-2-(nitromethyl)ornithine)cobalt(III) trichloride (2d). The amino acid rac.-2-(nitromethyl)ornithine (1b) was released by reducing complex 2d with aqueous ammonium sulfide. Complex 2d was expected to release 2-(nitromethyl)ornithine (1b) in hypoxic cells, where the amino acid could act as an inhibitor of ornithine decarboxylase. Preliminary data indicated that complex 2d was weakly cytotoxic in one cell type studied. Show more