合成及抗菌天然产物脂唑烷酮 A 的生物评价。
Synthesis and Biological Evaluation of the Antimicrobial Natural Product Lipoxazolidinone A.
机构信息
Department of Chemistry and Comparative Medicine Institute, North Carolina State University, 2620 Yarbrough Drive, Raleigh, NC, 27695, USA.
出版信息
Angew Chem Int Ed Engl. 2018 Jul 9;57(28):8682-8686. doi: 10.1002/anie.201805078. Epub 2018 Jun 10.
Abstract
Natural products have historically been a major source of antibiotics and therefore novel scaffolds are constantly of interest. The lipoxazolidinone family of marine natural products, with an unusual 4-oxazolidinone heterocycle at their core, represents a new scaffold for antimicrobial discovery; however, questions regarding their mechanism of action and high lipophilicity have likely slowed follow-up studies. Herein, we report the first synthesis of lipoxazolidinone A, 15 structural analogues to explore its active pharmacophore, and initial resistance and mechanism of action studies. These results suggest that 4-oxazolidinones are valuable scaffolds for antimicrobial development and reveal simplified lead compounds for further optimization.
摘要
天然产物一直是抗生素的主要来源，因此新型支架一直受到关注。脂氧恶唑烷酮类海洋天然产物，以其核心的不寻常的 4-恶唑烷酮杂环为代表，是一种新的抗菌发现的支架；然而，关于其作用机制和高亲脂性的问题可能减缓了后续研究。本文首次报道了脂氧恶唑烷酮 A 的全合成，合成了 15 个结构类似物，以探索其活性药效基团，并进行了初步的耐药性和作用机制研究。这些结果表明，4-恶唑烷酮是有价值的抗菌药物开发支架，并揭示了简化的先导化合物，以进一步优化。
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