Total Synthesis of Etnangien
Total Synthesis of Etnangien
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DOI：
10.1021/ja9056163
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发表时间：
2009-08-26
影响因子：
15
通讯作者：
Menche, Dirk
中科院分区：
文献类型：
--
作者：
Li, Pengfei;Li, Jun;Menche, Dirk
第一个全合成的强效rna聚合酶抑制剂etnangien被描述，它明确地建立了这种敏感的大环内酯类抗生素的相对和绝对构型。便捷和模块化合成的主要特点包括立体选择性底物控制的硼和锡介导的醛醇偶联，以设置具有高度立体选择性和产率的甲基和羟基立体中心的特征序列，构象受限底物的高效Heck大环化，以及后期引入不稳定侧链。趋同的方法应该适用于设计的类似物。
The first total synthesis of the potent RNA-polymerase inhibitor etnangien is described, which establishes unequivocally the relative and absolute configuration of this sensitive macrolide antibiotic. Key features of the expedient and modular synthesis include stereoselective substrate-controlled boron- and tin-mediated aldol couplings to set the characteristic sequences of methyl and hydroxyl bearing stereogenic centers with high degrees of stereoselectivity and yield, an efficient Heck macrocyclization of a conformationally restricted substrate, and a late-stage introduction of the labile side chain. The convergent approach should be amenable to designed analogues.