Models of the putative antimony( v )–diolate motifs in antileishmanial pentavalent antimonial drugs
Models of the putative antimony( v )–diolate motifs in antileishmanial pentavalent antimonial drugs
复制标题
抗地利什曼病五价锑药物中推定锑( v )-二醇基序的模型
DOI：
10.1039/d3dt01623d
复制
发表时间：
2023
影响因子：
4
通讯作者：
Johnstone, Timothy C.
中科院分区：
文献类型：
--
作者：
Lindquist-Kleissler, Brent;Johnstone, Timothy C.
五价锑剂是一种用于治疗被忽视的热带疾病利什曼病的含锑小分子药物，尽管其广泛使用了半个多世纪，但其结构仍然未知。这些药物是通过Sb（V）前体和糖衍生物的组合制备的，并且所提出的结构经常调用环状锑硼烷基序，其中邻位二醇盐配体螯合Sb（V）中心。作为更好地理解五价锑药物的结构的一步，一系列的环状有机锑硼烷跨越立体化学空间所提供的邻位二醇基序已被合成和表征。X射线晶体学和NMR光谱提供了明确的表征这些模型化合物的结构和二醇盐与Sb（V）中心的相互作用。特别值得注意的是在NMR光谱信号中观察到的作为二醇盐的立体化学的函数的系统趋势。这些模型化合物的光谱特征将为阐明五价锑药物的结构提供一个框架。
The structures of the pentavalent antimonials, small-molecule Sb-containing drugs used to treat the neglected tropical disease leishmaniasis, remain unknown despite their widespread use for over half a century. These drugs are prepared by combination of an Sb(V) precursor and a sugar derivative and proposed structures frequently invoke a cyclic stiborane motif in which a vicinal diolate ligand chelates an Sb(V) center. As a step towards better understanding the structures of the pentavalent antimonial drugs, a series of cyclic organostiboranes spanning the stereochemical space afforded by a vicinal diolate motif has been synthesized and characterized. X-ray crystallography and NMR spectroscopy provide unambiguous characterization of the structures of these model compounds and of the interaction of the diolate with the Sb(V) center. Particularly notable are the systematic trends observed in the NMR spectroscopic signals as a function of the stereochemistry of the diolate. The spectroscopic signatures identified with these model compounds will provide a framework for elucidating the structures of the pentavalent antimonial drugs.