Synthesis of neamine-derived pseudodisaccharides by stereo- and regio-selective functional group transformations.
Synthesis of neamine-derived pseudodisaccharides by stereo- and regio-selective functional group transformations.
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DOI：
10.1039/b907518f
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发表时间：
2009-09
影响因子：
3.2
通讯作者：
L. Pang;Dan-Jiao Wang;Jian Zhou;Li-he Zhang;X. Ye
中科院分区：
文献类型：
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作者：
L. Pang;Dan-Jiao Wang;Jian Zhou;Li-he Zhang;X. Ye
新胺通常是氨基糖苷类抗生素的核心结构。为了了解新胺的抗菌活性与官能团构型的关系，设计合成了一系列在2-脱氧链胺(2-DOS)环或糖环上进行官能团操作的新型新胺类似物。该合成方法包括催化费里尔II重排、立体和区域选择性官能团转化、糖基偶联反应和整体去保护等步骤来构建2-DOS衍生物。在合成的新胺类似物中，四个化合物与新胺具有相似的16S rRNA结合亲和力，而它们对18S rRNA的结合亲和力低于新胺，这意味着它们对哺乳动物的毒性较低。这一策略可能在其他新胺类化合物的化学合成和具有更高生物活性的新氨基糖苷类抗生素的合成中得到应用。
Neamine is normally found as a core structure of aminoglycoside antibiotics. In order to understand the relationship between the antibiotic activity and the configurations of the functional groups of neamine, a series of novel neamine analogues with functional group manipulations on the 2-deoxystreptamine (2-DOS) ring or the sugar ring were designed and synthesized. The synthetic approach involved the construction of 2-DOS derivatives by catalytic Ferrier II rearrangement, stereo- and regio-selective functional group transformations, glycosyl coupling reaction, and global deprotection. Of the synthetic neamine analogues, four compounds showed comparable 16S rRNA binding affinities with neamine, whereas they displayed lower binding affinities towards 18S rRNA than neamine, implying a lower toxicity to mammals. This strategy might have applications in the chemical synthesis of other neamine derivatives and new aminoglycoside antibiotics with improved biological activities.