Diazo Reagents with Small Steric Footprints for Simultaneous Arming/SAR Studies of Alcohol-Containing Natural Products via O-H Insertion
Diazo Reagents with Small Steric Footprints for Simultaneous Arming/SAR Studies of Alcohol-Containing Natural Products via O-H Insertion
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DOI：
10.1021/cb2002686
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发表时间：
2011-11-01
影响因子：
4
通讯作者：
Romo, Daniel
中科院分区：
文献类型：
--
作者：
Chamni, Supakarn;He, Qing-Li;Romo, Daniel
天然产品是必不可少的。基础细胞研究的工具，可识别医学相关的蛋白质靶标，并发现潜在的治疗线索。开发能够对天然产物进行温和和选择性衍生化的方法对于挖掘其丰富的信息内容仍然具有重要意义。在这里，我们描述了用于同时武装和结构活性关系的新型重氮试剂。含醇天然产物的 (SAR) 研究 具有小空间足迹，即 α-三氟乙基 (HTFB) 取代试剂 研究了几种天然产物（包括强效翻译抑制剂乳酰米霉素）的 Rh(II) 催化 0 H 插入反应，观察到有用的反应性以及化学和位点（化学位点）选择性 证明了与 FK506 和烟曲霉醇已知蛋白质靶标的差异结合，验证了α-三氟乙基衍生物较小空间足迹的优势。还描述了对叠氮苯基重氮试剂，该试剂将证明可用于低亲和力小分子蛋白质受体的光亲和标记。
Natural products are essential. tools for basic cellular studies leading to the identification of medically relevant protein targets', and the discovery of potential therapeutic leads. The development of methods that enable mild and selective derivatization of natural products continues to be of significant interest for mining their information-rich content. Herein, we describe novel diazo reagents for simultaneous arming and structure activity relationship. (SAR) studies of alcohol-containing natural products With a small steric footprint, namely, an alpha-trifluoroethyl (HTFB) substituted reagent The Rh(II)-catalyzed 0 H insertion reaction of several natural products, including the potent translation inhibitor lactimidomycin, was investigated, and useful reactivity and both chemo- and site (chemosite) selectivities were observed Differential binding to the known protein targets of both FK506 and fumagillol was demonstrated, validating the advantage of the smaller steric footprint of alpha-trifluoroethyl derivatives' A p-azidophenyl diazo reagent is also described that will prove useful for photoaffinity labeling of low affinity small, molecule protein receptors.