A Practical Enantioselective Synthesis of a Novel Peptide Deformylase Inhibitor

A practical synthesis of the peptide deformylase inhibitor LBM415,(2S)-N-(5-fluoro-1-oxido-2-pyridinyl)-1-[(2R)-2-[(formyl-hydroxyamino)methyl]-1-oxohexyl]-2-pyrrolidinecarboxamide, magnesium salt 11, is described. The key chiral intermediate, (2S)-N-(5-fluoro-2-pyridinyl)-1-[(2R)-2-[[formyl(phenylmeth-oxy)amino]methyl]-1-oxohexyl]-2-pyrrolidinecarboxamide 8, was made by coupling the corresponding amino acid 7 with the carboxamide 25 prepared from L-proline and 2-amino-5-fluoropyridine. Following oxidation of the pyridine nitrogen, selective hydrogenolysis of the benzyl group afforded the free acid of the drug substance, which was converted to the magnesium salt in situ with magnesium chloride. The product was obtained in an overall yield of 16% with an ee > 99%.