Gram-positive bacteria are among the most common human pathogens associated with clinical infections which range from mild skin infections to sepsis. Resistance towards existing class of drugs by Gram-positive bacteria including methicillin resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis (MRSE) and vancomycin resistant enterococci (VRE) is a growing concern. There is an urgent need to discover new antibiotics which are active against resistant strains of Gram positive bacteria. We report herein a novel class of spiropyrimidinetrione oxazolidinone derivatives as novel antibacterial agents. Key step towards the synthesis of title compounds involved the use of tert-amino reaction with [1,5]-hydride shift leading to the new CC bond formation. Compound 30n has demonstrated potent antibacterial activity against a panel of Gram-positive microbial strains including MRSA, MRSE, and LNZ and vancomycin resistant strains of E. faecalis. Further, molecular docking studies suggest that 30n has binding mode similar to that of LNZ in 50S RNA ribosome.

革兰氏阳性细菌是与临床感染相关的最常见的人类病原体，其范围从轻度皮肤感染到败血症。革兰氏阳性细菌（包括耐甲氧西林的金黄色葡萄球菌（MRSA），表皮葡萄球菌（MRSE）和耐万古霉素的肠球菌（VRE））对现有药物的耐药性日益引起人们的关注。迫切需要发现对革兰氏阳性细菌的耐药菌株具有活性的新抗生素。我们在本文中报道了作为新型抗菌剂的一类新的螺嘧啶三酮恶唑烷酮衍生物。向标题化合物的合成关键步骤涉及使用的叔-[氨基]与[1,5]-氢化物位移的氨基反应导致新的C C键形成。化合物30n已显示出对包括MRSA，MRSE和LNZ在内的一系列革兰氏阳性微生物菌株和粪肠球菌的万古霉素耐药菌株的有效抗菌活性。此外，分子对接研究表明30n具有与50S RNA核糖体中的LNZ相似的结合模式。