Synthesis of kanamycin A derivatives by regioselective masking drug resistant enzymes targeting hydroxyl groups

选择性封闭卡那霉素A耐药酶羟基衍生物的合成(英文)

The 3＇-OH, 4＇-OH and 2＂-OH of kanamycin A were modified in search of new aminoglycosides to overcome resistant enzymes, ANTs and APHs. The key intermediate was a dibenzylidene-protected derivative of kanamycin A. The aimed sites were masked by benzyl, methyl and allyl groups. Multi-step reactions gave the desired aminoglycoside derivatives but showed less antibiotic activity than kanamycin A.

为寻找能抵抗耐药酶作用的氨基糖苷类抗生素,本文对卡那霉素A的3′-OH,4′-OH和2″-OH位点进行了修饰。合成路线中的关键中间体为引入双苄叉保护基的卡那霉素A衍生物。目标羟基通过苄基化,甲基化和烯丙基化的方法进行修饰。最后通过多步反应脱保护,得到目标产物。活性结果显示,目标产物对敏感菌和耐药菌未显示出良好的抗菌活性。