Kamachi H, Okita T, Yamasaki T, Naito T
Bristol-Myers Research Institute, Ltd., Tokyo Research Center, Japan.
J Antibiot (Tokyo). 1990 Jul;43(7):820-9. doi: 10.7164/antibiotics.43.820.
A novel direct introduction of a formamido group into the 7 alpha (6 alpha)-position of cephalosporins (penicillins) was achieved by treatment of 7 beta (6 beta)-[(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadien-1- ylidene)methylimino]cephem (penam) esters with N,N-bis(trimethylsilyl)formamide, followed by deblocking with Girard reagent T to give the corresponding 7 alpha (6 alpha)-formamido-7 beta (6 beta)-amino derivatives. Three 7 alpha-formamidocephalosporins were prepared by the conventional N-acylation of 7 alpha-formamidocephem. All of them were resistant to beta-lactamases, showing similar MIC values against both of a pair of a beta-lactamase-producing strain and the corresponding non or low-producing strain of the same species of bacteria, when tested on Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Enterobacter cloacae and Citrobacter freundii.
通过用N，N-双（三甲基硅基）甲酰胺处理7β（6β）-[（3，5-二叔丁基-4-氧代-2，5-环己二烯-1-亚基）甲基亚氨基]头孢烯（青霉烯）酯，然后用吉拉德试剂T脱保护，实现了将甲酰胺基新颖地直接引入头孢菌素（青霉素）的7α（6α）位，得到相应的7α（6α）-甲酰胺基-7β（6β）-氨基衍生物。通过7α-甲酰胺基头孢烯的常规N-酰化反应制备了三种7α-甲酰胺基头孢菌素。当在金黄色葡萄球菌、肺炎克雷伯菌、大肠杆菌、奇异变形杆菌、普通变形杆菌、摩根氏摩根菌、阴沟肠杆菌和弗氏柠檬酸杆菌上进行测试时，它们均对β-内酰胺酶具有抗性，对一对产β-内酰胺酶菌株和同一细菌物种相应的非产或低产菌株显示出相似的最低抑菌浓度值。
