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Bioinspired Discovery of Chemical Reactions and Biological Probes

机译:生物启发发现化学反应和生物探针

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Indole alkaloids are a large and diverse family of natural products that display a variety of medicinal properties. These natural products have consistently proven difficult to synthesize, due in large part to their complex skeletons and sterically hindered quaternary carbon centers. We have reported the efficient syntheses of polycyclic indole derivatives using gold catalysts, which selectively activate alkynylindoles for tandem cyclizations with high stereospecificity. The facile nature of these methods has allowed previously implausible diversity syntheses to be carried out yielding a large and highly diverse library of polycyclic indolines. Biological screenings revealed compounds that selectively re-sensitize methicillin-resistant Staphylococcus aureus (MRSA) to -lactam antibiotics, which may herald a new way of staving off the incursion of drug-resistant strains of common human pathogens.
机译:吲哚生物碱是具有多种医学特性的大量天然产品家族。一直以来,这些天然产物被证明很难合成,这在很大程度上是由于它们复杂的骨架和空间受阻的季碳中心。我们已经报道了使用金催化剂有效地合成多环吲哚衍生物,所述金催化剂选择性地激活炔基吲哚用于具有高立体特异性的串联环化。这些方法的简便性质使得先前难以置信的多样性合成得以进行,从而产生了大型且高度多样化的多环吲哚啉文库。生物筛选显示了可以选择性地使耐甲氧西林的金黄色葡萄球菌(MRSA)重新敏感于-lactam抗生素的化合物,这可能预示了一种新的方法,可以避免入侵普通人类病原体的耐药菌株。

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