Copper-Catalyzed Double Additions and Radical Cyclization Cascades in the Re-Engineering of the Antibacterial Pleuromutilin.
Copper-Catalyzed Double Additions and Radical Cyclization Cascades in the Re-Engineering of the Antibacterial Pleuromutilin.
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DOI：
10.1002/chem.201504343
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发表时间：
2016-01-04
期刊：
影响因子：
--
通讯作者：
Procter DJ
中科院分区：
文献类型：
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作者：
Ruscoe RE;Fazakerley NJ;Huang H;Flitsch S;Procter DJ
一般的合成序列，包括简单的准备起始材料，提供了快速获得不同的，新的三环结构的途径，灵感来自于截胸菌素。SMII介导的双醛自由基环化级联反应，使用新的一锅铜催化的双有机镁与β-氯环己酮的加成反应制备，具有完全的序列选择性和典型的高非对映控制，以提供目标核心的类似物。我们的权宜之计(约7个 步骤)允许非传统的、从头合成的方法获得重要抗菌物质的类似物，这些类似物不能通过半合成从天然产品中制备。
A general synthetic sequence involving simply prepared starting materials provides rapid access to diverse, novel tricyclic architectures inspired by pleuromutilin. SmII‐mediated radical cyclization cascades of dialdehydes, prepared using a new, one‐pot, copper‐catalyzed double organomagnesium addition to β‐chlorocyclohexenone, proceed with complete sequence selectivity and typically with high diastereocontrol to give analogues of the target core. Our expedient approach (ca. 7 steps) allows non‐traditional, de novo synthetic access to analogues of the important antibacterial that can′t be prepared from the natural product by semisynthesis.