Biomimetically inspired asymmetric total synthesis of (+)-19-dehydroxyl arisandilactone A.
Biomimetically inspired asymmetric total synthesis of (+)-19-dehydroxyl arisandilactone A.
复制标题
( )-19-脱羟基阿里山二内酯 A 的仿生启发不对称全合成
DOI：
10.1038/ncomms14233
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发表时间：
2017-01-31
影响因子：
16.6
通讯作者：
Yang Z
中科院分区：
文献类型：
--
作者：
Han YX;Jiang YL;Li Y;Yu HX;Tong BQ;Niu Z;Zhou SJ;Liu S;Lan Y;Chen JH;Yang Z
复杂的天然产物是一种被证实的丰富的疾病调节药物来源，也是研究化学生物学和药物发现的有效工具。复杂天然产物的结构通常被认为是有效化学合成的重要障碍。在这里，我们描述了一种简明高效的不对称合成19-脱羟基五味子内酯A-，它属于从药用植物五味子中分离得到的一类结构独特、高含氧量的去甲三萜类化合物。这一合成是通过Homo-Michael反应、串联的Retro-Michael/Michael反应和铜催化的分子内环丙烷化作为关键步骤进行的。密度泛函理论(DFT)计算支持Homo-Michael反应和串联Retro-Michael/Michael反应的机理。所开发的化学方法可用于五味子科去甲三萜的合成。芳香内酯A是一种具有复杂的氧桥联三环碳核的天然产物，使其成为全合成中的一个具有挑战性的目标。本文报道了其19-脱羟基衍生物的不对称全合成，关键步骤为同-Michael反应和串联Retro-Michael/Michael反应。
Complex natural products are a proven and rich source of disease-modulating drugs and of efficient tools for the study of chemical biology and drug discovery. The architectures of complex natural products are generally considered to represent significant barriers to efficient chemical synthesis. Here we describe a concise and efficient asymmetric synthesis of 19-dehydroxyl arisandilactone A—which belongs to a family of architecturally unique, highly oxygenated nortriterpenoids isolated from the medicinal plant Schisandra arisanensis. This synthesis takes place by means of a homo-Michael reaction, a tandem retro-Michael/Michael reaction, and Cu-catalysed intramolecular cyclopropanation as key steps. The proposed mechanisms for the homo-Michael and tandem retro-Michael/Michael reactions are supported by density functional theory (DFT) calculation. The developed chemistry may find application for the synthesis of its other family members of Schisandraceae nortriterpenoids. Arisandilactone A is a natural product with a complex oxa-bridged tricyclic carbon core, making it a challenging target in total synthesis. Here the authors report an asymmetric total synthesis of its 19-dehydroxy derivative, with homo-Michael and tandem retro-Michael/Michael reactions as key steps.