Selective transformations of complex molecules are enabled by aptameric protective groups
Selective transformations of complex molecules are enabled by aptameric protective groups
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DOI：
10.1038/nchem.1402
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发表时间：
2012-10-01
期刊：
影响因子：
21.8
通讯作者：
Herrmann, Andreas
中科院分区：
文献类型：
--
作者：
Bastian, Andreas A.;Marcozzi, Alessio;Herrmann, Andreas
药物发现的新趋势促使人们对天然产物作为化学多样性和铅结构的来源重新产生兴趣。然而，由于许多天然化合物的结构复杂，衍生物的合成并不容易实现。在这里，我们展示了一种概念上的新方法，使用寡核苷酸作为适配体保护基团。这些化合物通过复杂分子中的非共价相互作用阻断几种功能，并在一个合成步骤中实现天然抗生素的高度化学和区域选择性衍生化（> - 99%），转化率高达83%。这项技术揭示了胺基抗生素中重要的结构-活性关系，有助于加速发现新的生物活性结构，并避免潜在的昂贵和繁琐的合成路线。
Emerging trends in drug discovery are prompting a renewed interest in natural products as a source of chemical diversity and lead structures. However, owing to the structural complexity of many natural compounds, the synthesis of derivatives is not easily realized. Here, we demonstrate a conceptually new approach using oligonucleotides as aptameric protective groups. These block several functionalities by non-covalent interactions in a complex molecule and enable the highly chemo-and regioselective derivatization (>99%) of natural antibiotics in a single synthetic step with excellent conversions of up to 83%. This technique reveals an important structure-activity relationship in neamine-based antibiotics and should help both to accelerate the discovery of new biologically active structures and to avoid potentially costly and cumbersome synthetic routes.