热诱导和光诱导铜促进的 C-Se 键形成：2-烷基-1,2-苯并硒唑-3(2H)-酮的合成及其对结核分枝杆菌的评价。
Thermal and Photoinduced Copper-Promoted C-Se Bond Formation: Synthesis of 2-Alkyl-1,2-benzisoselenazol-3(2H)-ones and Evaluation against Mycobacterium tuberculosis.
机构信息
Department of Chemistry and Biochemistry, The University of Toledo , 2801 W. Bancroft Street, Toledo, Ohio 43606, United States.
Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University , Fort Collins, Colorado 80523, United States.
出版信息
J Org Chem. 2017 Apr 7;82(7):3844-3854. doi: 10.1021/acs.joc.7b00440. Epub 2017 Mar 20.
2-Alkyl-1,2-benzisoselenazol-3(2H)-ones, represented by ebselen (1a), are being studied intensively for a range of medicinal applications. We describe both a new thermal and photoinduced copper-mediated cross-coupling between potassium selenocyanate (KSeCN) and N-substituted ortho-halobenzamides to form 2-alkyl-1,2-benzisoselenazol-3(2H)-ones containing a C-Se-N bond. The copper ligand (1,10-phenanthroline) facilitates C-Se bond formation during heating via a mechanism that likely involves atom transfer (AT), whereas, in the absence of ligand, photoinduced activation likely proceeds through a single electron transfer (SET) mechanism. A library of 15 2-alkyl-1,2-benzisoselenazol-3(2H)-ones was prepared. One member of the library was azide-containing derivative 1j that was competent to undergo a strain-promoted azide-alkyne cycloaddition. The library was evaluated for inhibition of Mycobacterium tuberculosis (Mtb) growth and Mtb Antigen 85C (Mtb Ag85C) activity. Compound 1f was most potent with a minimal inhibitory concentration (MIC) of 12.5 μg/mL and an Mtb Ag85C apparent IC of 8.8 μM.
2- 烷基-1,2-苯并异硒唑-3(2H)-酮，以依布硒啉（1a）为代表，正在被广泛研究以应用于各种医学用途。我们描述了一种新的热诱导和光诱导的铜介导的交叉偶联反应，该反应发生在 KSeCN 和 N-取代邻卤代苯甲酰胺之间，形成含有 C-Se-N 键的 2- 烷基-1,2-苯并异硒唑-3(2H)-酮。铜配体（1,10-菲咯啉）通过可能涉及原子转移（AT）的机制促进加热过程中的 C-Se 键形成，而在没有配体的情况下，光诱导激活可能通过单电子转移（SET）机制进行。我们制备了 15 种 2- 烷基-1,2-苯并异硒唑-3(2H)-酮的文库。文库中的一个成员是含有叠氮化物的衍生物 1j，它能够进行应变促进的叠氮化物-炔烃环加成反应。该文库用于抑制结核分枝杆菌（Mtb）生长和 Mtb Ag85C（Mtb Ag85C）活性的评估。化合物 1f 的抑制活性最强，最小抑菌浓度（MIC）为 12.5 μg/mL，Mtb Ag85C 的表观 IC 为 8.8 μM。
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