Synthesis of Norbornane Bisether Antibiotics via Silver-mediated Alkylation.
Synthesis of Norbornane Bisether Antibiotics via Silver-mediated Alkylation.
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DOI：
10.1039/c5ra03321g
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发表时间：
2015
期刊：
影响因子：
3.9
通讯作者：
Pfeffer FM
中科院分区：
文献类型：
--
作者：
Hickey SM;Ashton TD;White JM;Li J;Nation RL;Yu HY;Elliott AG;Butler MS;Huang JX;Cooper MA;Pfeffer FM
合成了一系列的双醚双胍类抗菌剂，并对其抗菌性能进行了评价。使用威廉姆森方法学不能成功地进行关键的转化--十六烷二醇6-的双烷基化，但使用Ag 2 O介导的烷基化已经完成。进一步官能化，以纳入两个胍基团产生了一系列结构刚性阳离子两亲物，其中几个（16 d，16 g和16 h）表现出抗生素活性。例如，化合物16 d对包括铜绿假单胞菌（MIC = 8 μg/mL）、大肠杆菌（MIC = 8 μg/mL）和耐甲氧西林金黄色葡萄球菌（MIC = 8 μg/mL）在内的广泛范围的细菌具有活性。
A small series of norbornane bisether diguanidines have been synthesized and evaluated as antibacterial agents. The key transformation—bisalkylation of norbornane diol 6—was not successful using Williamson methodology but has been accomplished using Ag2O mediated alkylation. Further functionalization to incorporate two guanidinium groups gave rise to a series of structurally rigid cationic amphiphiles; several of which (16d, 16g and 16h) exhibited antibiotic activity. For example, compound 16d was active against a broad range of bacteria including Pseudomonas aeruginosa (MIC = 8 µg/mL), Escherichia coli (MIC = 8 µg/mL) and methicillin-resistant Staphylococcus aureus (MIC = 8 µg/mL).