通过格拉布催化剂复分解反应对海绵胺A进行合成修饰。具有增强抗菌和抗原生动物特性的新型结构。
Synthetic modification of manzamine A via Grubbs metathesis. Novel structures with enhanced antibacterial and antiprotozoal properties.
作者信息
Winkler Jeffrey D, Londregan Allyn T, Hamann Mark T
机构信息
Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
出版信息
Org Lett. 2007 Oct 25;9(22):4467-9. doi: 10.1021/ol701799c. Epub 2007 Oct 5.
Abstract
A strategy for the structural modification of biologically important alkene-containing natural products via ring-opening olefin metathesis is described. Exposure of manzamine A 1 to the second-generation Grubbs catalyst in the presence of ethylene leads to the formation of 2 and 4. The antibacterial activity of the novel manzamine analogue 2 (IC50=0.10 nM) against Mycobacterium intracellulare is ca. 2-fold more potent than that of ciprofloxacin (IC50=0.18 nM), a drug that is frequently used against antibiotic-resistant infections.
摘要
描述了一种通过开环烯烃复分解对具有生物学重要性的含烯烃天然产物进行结构修饰的策略。在乙烯存在下，将曼氏胺A 1暴露于第二代格拉布催化剂会生成2和4。新型曼氏胺类似物2（IC50 = 0.10 nM）对胞内分枝杆菌的抗菌活性约为环丙沙星（IC50 = 0.18 nM）的2倍，环丙沙星是一种常用于治疗抗生素耐药感染的药物。
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