Design And Synthesis Novel Peptide Deformylase Inhibitors And (R)-Ethyl Piperidine-3-acetate

Since the discovery and application of antibiotics, our human can struggle with the death from bacteria infectious diseases. However, antibiotic-resistant bacteria were generated because of the abuse of antibiotics. Quite a number of antibiotic-resistant bacteria emerge until now.Peptide deformylase (PDF) inhibitor is one kind of antibacterial drug with novel mechanism. PDF plays a critical role in bacterial protein synthesis while it does not exist in any mammalian cell. PDF inhibitor prevent PDF from catalyzing the deformyl process during bacterial protein synthesis to kill the bacteria selectively.Based on LBM415(discovered by Vicuron pharmaceuticals, in collaboration with Novartis), we designed novel PDF inhibitors contains4-methyleneproline structure, and proposed new route to synthesize the PDF inhibitor. The biological test shows some of the in vitro activity. The compound NO.2301is better than the antibiotic drugs which are mainly used in vitro activity.Besides that, we have synthesis the two series novel PDF inhibitor which contain the cis-4-fluro-L-proline and cis-4-methyl-L-proline. The biological test is in progress.We have make great progress in synthesis of the intermediates of PDF inhibitor. Some the intermediates can be synthesized in large scale.Ethyl (R)-piperidine-3-acetate is one of important medicine intermediate of piperidine derivatives, which is mainly used in the synthesis of neurological drugs. In this paper, we report a practical and scalable synthesis route of Ethyl (R)-piperidine-3-acetate from very cheap3-pyridylacetic acid hydrochloride in four steps with high yield。Ethyl (S)-piperidine-3-acetate can also be successfully synthesized similarly。...