Resolution of the enantiomers of various α-substituted ornithine and lysine analogs by high-performance liquid chromatography with chiral eluant and by gas chromatography on Chirasil-Val

A reversed-phase high-performance liquid chromatography method, with l-proline and copper as chiral mobile phase, is described for the enantiomeric resolution of various α-substituted ornithine and lysine analogs. Although ornithine gives no separation with the chiral eluant used, excellent resolutions are obtained for various α-alkyl-, α-halogenomethyl-, α-vinyl-, and α-ethynyl-substituted ornithines. Similar separations are also observed for the dehydroornithine and lysine analogs. Gas chromatography on a chiral stationary phase, Chirasil-Val, allows the resolution of the ornithine and lysine analogs after derivatization into the monofluoroacyl derivatives of their corresponding lactams. No resolution or only a poor resolution is obtained by GC on Chirasil-Val for the dehydroornithine analogs as their di- N-perfluoroacyl alkyl esters. The chiral eluant HPLC procedure is easily scaled up for the semipreparative resolution of several ornithine analogs, i.e., α-fluoromethylornithine, α-difluoromethylornithine, α-chlorofluoromethylornithine, and α-fluoromethyldehydroornithine, which are known as potent ornithine decarboxylase inhibitors in vitro and in vivo.