Total synthesis and biological evaluation of transvalencin Z.
Total synthesis and biological evaluation of transvalencin Z.
复制标题
反价蛋白Z的全合成及生物学评价。
DOI：
10.1021/np200972s
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发表时间：
2012
影响因子：
5.1
通讯作者：
Aldrich,CourtneyC
中科院分区：
文献类型：
--
作者：
Nelson,KathrynM;Salomon,ChristineE;Aldrich,CourtneyC
耐药结核病正在全球流行，迫切需要确定新的治疗方法来治疗疾病。Transvalencin Z(1)是一种来自于nocardia transvalenensis的天然产物，对耻垢分枝杆菌具有较强的选择性抑菌活性，是研究其结构活性和作用机制的理想靶点。通过化学合成、高效液相色谱保留时间和旋光度测定，确定了反价菌素Z的四种可能的非对映体的绝对构型。令人惊讶的是，没有一种反valencin Z非对映体对一组微生物病原体表现出任何抑制活性，包括几种分枝杆菌。
The emerging global epidemic of drug-resistant tuberculosis has created an urgent need to identify novel therapeutic approaches for disease treatment. Transvalencin Z (1) is a natural product fromNocardia transvalensiswith relatively potent and selective antimycobacterial activity againstMycobacterium smegmatis, making it an attractive target for structure–activity and mechanism of action studies. The total synthesis of the four possible diastereomers of transvalencin Z was completed (1a–d), and the absolute configurations were defined using chemical synthesis, HPLC retention times, and optical rotation measurements. Surprisingly, none of the transvalencin Z diastereomers exhibited any inhibitory activity against a panel of microbial pathogens, including several species of mycobacteria.