当前位置: X-MOL 学术ACS Cent. Sci. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Catalysis-Enabled Access to Cryptic Geldanamycin Oxides.
ACS Central Science ( IF 18.2 ) Pub Date : 2020-02-24 , DOI: 10.1021/acscentsci.0c00024
Margaret J Hilton 1 , Christopher M Brackett 2 , Brandon Q Mercado 1 , Brian S J Blagg 2 , Scott J Miller 1
Affiliation  

Catalytic, selective modifications of natural products can be a fertile platform for not only unveiling new natural product analogues with altered biological activity, but also for revealing new reactivity and selectivity hierarchies for embedded functional groups in complex environments. Motivated by these intersecting aims, we report site- and stereoselective oxidation reactions of geldanamycin facilitated by aspartyl-peptide catalysts. Through the isolation and characterization of four new geldanamycin oxides, we discovered a synergistic effect between lead peptide-based catalysts and geldanamycin, resulting in an unexpected reaction pathway. Curiously, our discoveries would likely not have been possible absent the attractive noncovalent interactions intrinsic to both the catalysts and the natural product. The result is a set of new “meta” catalytic reactions that deliver both unknown and previously incompletely characterized geldanamycin analogues. Enabled by the catalytic, site-selective epoxidation of geldanamycin, biological assays were carried out to document the bioactivities of the new compounds.

中文翻译:

催化访问隐匿性格尔德霉素氧化物。

天然产物的催化选择性修饰可以成为一个肥沃的平台,不仅可以揭示具有改变的生物活性的新天然产物类似物,而且可以揭示复杂环境中嵌入式官能团的新反应性和选择性层次。受这些相交目标的影响,我们报告了由天冬氨酰-肽催化剂促进的格尔德霉素的定点和立体选择性氧化反应。通过分离和表征四种新的格尔德霉素氧化物,我们发现了基于铅肽的催化剂和格尔德霉素之间的协同作用,从而导致了意外的反应途径。奇怪的是,如果没有催化剂和天然产物固有的有吸引力的非共价相互作用,我们的发现将不可能实现。结果是产生了一组新的“元”催化反应,可同时传递未知的和以前不完整表征的格尔德霉素类似物。通过格尔德霉素的催化,位点选择性环氧化,进行了生物学测定以证明新化合物的生物活性。
更新日期:2020-03-26
down
wechat
bug