Synthesis and inhibitory properties of α(chlorofluoromethyl)-α-amino acids, a novel class of irreversible inactivators of decarboxylases

Abstract

The synthesis of α-(chlorofluoromethyl)-ornithine 7, -metatyrosine 8 and -glutamic acid 14 is described. Separation of diastereoisomers and relative configuration assignment by X-ray analysis are reported. Assignment of absolute configuration of the four enantiomers of α-(chlorofluoromethyl)-ornithine 7 is also described. The inhibitory properties against ornithine decarboxylase, aromatic amino acid decarboxylase and glutamate decarboxylase are reported in terms of diastereoselectivity (8 and 14) or enantioselectivity (7).