11-Step enantioselective synthesis of (-)-lomaiviticin aglycon.
11-Step enantioselective synthesis of (-)-lomaiviticin aglycon.
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DOI：
10.1021/ja200034b
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发表时间：
2011-05-18
影响因子：
15
通讯作者：
Gholap SL
中科院分区：
文献类型：
--
作者：
Herzon SB;Lu L;Woo CM;Gholap SL
洛麦维菌素A和洛麦维菌素B是从一株小单孢菌中分离出来的复杂的抗肿瘤抗生素。几种不同寻常的结构特征的结合使得lomaiviticins成为化学合成的极具挑战性的靶标。我们报道了一条11步，对映体选择性合成洛麦维星苷元的路线。我们的路线是通过两个等价的单体中间体的后期立体选择性二聚反应进行的，这种转化可能与天然产物的生物合成相似。我们描述的路线是可扩展和收敛的，它为确定这些天然产物的作用模式奠定了基础。
Lomaiviticins A and B are complex antitumor antibiotics that were isolated from a strain of Micromonospora. A confluence of several unusual structural features renders the lomaiviticins exceedingly challenging targets for chemical synthesis. We report an 11-step, enantioselective synthetic route to lomaiviticin aglycon. Our route proceeds by late-stage, stereoselective dimerization of two equivalent monomeric intermediates, a transformation that may share parallels with the natural products’ biosyntheses. The route we describe is scalable and convergent, and it lays the foundation for determination of the mode of action of these natural products.