Synthesis Of New 2-Methylene-Substituted Cephalosporins

Cephalosporin drugs are a kind ofβ-lactam antibiotics, which are welcomed by the majority of patients with the advantages of strong, broad spectrum antibiotic, high stability toβ-lactamase, low rate of resistance, low toxicity of clinical and good effect. According to foreign literatures, the series of 2-methylene-substituted compounds are prond to enhance theβ-lactamase suppression. However,study on these compounds is still blank in our country.In this paper, 7 - amino acid cephalosporins (7-ACA) is selected as one of the starting materials. After reactions such as acylation, esterification, oxidation, mannich condensation, reduction, the deprotection of carboxylic ester, four 2-methylene-subs- -tituted cephalosporins are obtaind whose yields were 31.1%,23.8%, 20.7% and 19.3% (7-ACA as benchmark) respectively. This article also provides a new method to synthesize 2-methylene-substituted cephalosporins from 4-Methoxybenzyl-3- chloromethyl-7-(2-phenylacetamido)-3-cephem-4-carboxylate (GCLE). a new 2- methylene-substituted conpound is converted from GCLE through the reactions such as iodization, pro-nuclear replacement, oxidation, mannich condensation, reduction with the yield 18.4% (GCLE as benkmark).These compounds had never reported in any literatures. The structures of these new compounds are confirmed by HPLC, 1H-NMR and other analytical tools.These new antibacterial compounds can be further carried out in experiments of its biological activity and stability, to determine whether they can be used as new clinicaldrugs.They also can be used as a serials of new intermediates for further refine to access to new compounds.