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首页> 外文期刊>Chemistry: A European journal >Synthesis and Evaluation of Novel Analogues of Ripostatins
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Synthesis and Evaluation of Novel Analogues of Ripostatins

机译：Ripostatins新型类似物的合成与评价

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摘要

Ripostatins are polyene macrolactones isolated from the myxobacterium Sorangium cellulosum. They exhibit antibiotic activity by inhibiting bacterial RNA polymerase (RNAP) through a binding site and mechanism that are different from those of current antibacterial drugs. Thus, the ripostatins serve as starting points for the development of new anti-infective agents with a novel mode of action. In this work, several derivatives of ripostatins were produced. 15-Desoxyripostatin A was synthesized by using a one-pot carboalumination/cross-coupling. 5,6-Dihydroripostatin A was constructed by utilizing an intramolecular Suzuki crosscoupling macrolactonization approach. 14,14’-Difluororipostatin A and both epimeric 14,14’-difluororipostatins B were synthesized by using a Reformatsky type aldol addition of a haloketone, Stille cross-coupling, and ring-closing metathesis. The RNAP-inhibitory and antibacterial activities are presented. Structure–activity relationships indicate that the monocyclic keto-ol form of ripostatin A is the active form of ripostatin A, that the ripostatin C5–C6 unsaturation is important for activity, and that C14 geminal difluorination of ripostatin B results in no loss of activity.
机译：Ripostatins是从粘质纤维素纤维素中分离的多烯大内酯。它们通过与当前抗菌药物不同的结合位点和机制抑制细菌RNA聚合酶（RNAP），从而表现出抗生素活性。因此，核苷可作为开发具有新型作用方式的新型抗感染剂的起点。在这项工作中，产生了核苷的几种衍生物。通过一锅碳铝化/交叉偶联合成15-脱氧核糖核酸A。利用分子内Suzuki交叉偶联大内酯化方法构建了5，6-二氢核蛋白A。通过使用卤代酮的Reformatsky型羟醛加成，Stille交叉偶联和闭环易位合成了14,14'-Difluororipostatin A和两种14,14'-difluororipostatinsB。介绍了RNAP抑制和抗菌活性。结构与活性的关系表明，ripostatin A的单环酮醇形式是ripostatin A的活性形式，ripostatin C5-C6的不饱和度对活性很重要，并且C14宝石双氟化的ripostatin B不会造成活性损失。

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