Study On The Synthesis Of Anti-tuberculosis Bacteria Natural Product Pyridomycin

Tuberculosis(TB)caused by Mycobacterium tuberculosis(MTB)infection has a serious impact on people’s health and life.The increasingly severe multi drug resistant or rifampicin resistant tuberculosis(MDR/RR-TB)is a great challenge for tuberculosis control.The development of drugs against drug-resistant tuberculosis is important for the prevention and treatment of multi drug resistant or rifampicin resistant tuberculosis.Pyridomycin is a natural product was isolated from streptomycin 6706 in 1953.It is a cyclic ester peptide with Anti-Mycobacterium activity.The structural characteristics of pyridomycin include an unnatural amino acid fragment with multiple chiral centers,C1-C2 enol ester structure and 12 membered macrocyclic structure.In 2011,Stewart research group showed that the natural product can inhibit the formation of bacterial membrane by acting on Inh A target,and has good inhibitory activity on isoniazid resistant strains with kat G mutation.we designed a library of macrocyclic products by modifing C2 site of pyridomycin with different amino acids and small molecular compounds with functional groups based on the structure and the related structure-activity relationship of pyridomycin in literature.In this paper,the synthesis route of pyridomycin C2 amino substituted macroring structure was designed.The macrocyclic products D-Pro-8,L-Pro-8,D-Pip-8 and L-Pip-8,substituted by D,L-piperidine-2-formic acid and D,L-proline at C2 site were successfully prepared.At the same time,3-hydroxy-2-pyridinic acid and3-pyridine in the structure of pyridomycin were considered as the characteristic structures of biological activity.In this paper,four small molecule compounds with functional groups were designed and prepared.