Studies On Synthesis Of An Analogue Of Cefpirome

Since the antibacterial activity and pharmacokinetics of cephalosporin antibioticschange greatly according to the changes of C-3 substituents, C-3 modification hasbeen an emphasis in the research and development of cephalosporin antibiotics. Agood example of C-3 modification is cefpirome, a representative drug of thefourth-generation cephalosporins. It stands a good chance that new compounds havingantibacterial activity will be found in cefpirome analogues whose C-3' substituents arepyridine derivatives. Thus the syntheses of cefpirome analogues are highlymeaningful. And the synthesis of 2,3-cyclopentenopyridine, a key side chain ofcefpirome, also caught much attention in the areas of cephalosporin antibiotics.Two synthetic routes for 2,3-cyclopentenopyridine were studied in this paper.Firstly, 2,3-cyclopentenopyridine was obtained in the yield of 21.1% throughcondensation, dehydrobromination, thermal rearrangement starting from cyclopentone.And it was also obtained in the yield of 20.8% through replacement,dehydrobromination, thermal rearrangement starting from phthalic anhydride.Concerning the synthesis of cefpirome analogue, three synthetic routes werestudied. The route employing GCLE as the starting material was emphaticallyexamined. After replacement of C-Cl of GCLE with iodide, followed by substitutionby pyridine, deprotection of carboxyl group, hydrolysis of 7-phenylacetamido andreaction with MAEM, the target molecular 7-[2-(2-aminothiazol-4-yl)-2-(Z)-oxyiminoacetamido]-3-(1-pyridiniomethyl)-ceph-3-em-4-carboxylate was obtained inthe yield of 65.2%. In the other two methods, the yield of final product was 10.4%and 54.5% on the basis of cefotaxime.