Carbapenem Antibiotics Biapenem (biapenem,) And 1,3,4 - Oxadiazole Azole-type Synthesis Of New Compounds And Antibacterial Activity

Carbapenem is a novel class of p-lactam antibiotics developed in 1970's, which have used in clinical treatment of severe bacterial infections caused by multidrug resistant strains. Carbapenem was characterized by the presence of a P-lactam ring with a carbon instead of sulfone in the 1-position of the thyazolidinic moiety and an unsaturated bond between C-2 and C-3. Carbapenem The chemical structure of carbapenems is similar to the combination of the thiazolidine ring in penicillin and the dihydrothiazine ring in cephalosporins. Carbapenems are widely researched due to their high activity against bacteria, wide antibacterial spectrum and the stability to β-lactamases. Biapenem which are the fifth carbapenem introduced into clinical practice in Japan in March 2002. Biapenem requires no coadministration drug, Biapenem is stable to β-lactamases and is superior or equal to Imipenem in antibacterial activity against gram-positive, gram-negative bacteria, aerobes and anaerobes.Our research was focused on the new synthetic route of Biapenem. The key intermediate 6,7-dihydro-6-mercapto-5H-pyrazolo[1,2--α][1,2,4]-triazolium chloride was synthesized from hydrazine via condensation ,allylation , deprotection of ketimine, bromination, cyclization , thioacetation , methanolysis, oxidation,deformylation,cyclization and reduction . Our research also focused on the joint between the carbapenem bicyclic nuclus and the side chain.We synthesized the carbapenem bicyclic nuclus of carboxylic group protected allyl by new methods. The process is moderate and simpler to industry with consumption.Since the carbapenems on sale such as Imipenem and Meropenem were lack of effective antibacterial activity against metnicillin-resistant staphylococcus aureus (MRSA) , so we focused on the design and synthesis of anti-MRSA carbapenem derivatives. The prepared side chains of 2-(derived phenyl)-5-methyl mercapt-1,3,4-oxodiazole were introduced into the C-2 of 1 β -methyl carbapenem bicyclic nuclus. After removal the protected group , we gain...