Catalytic Asymmetric Synthesis of Mixed 3,3′-Bisindoles and Their Evaluation as Wnt Signaling Inhibitors
Catalytic Asymmetric Synthesis of Mixed 3,3′-Bisindoles and Their Evaluation as Wnt Signaling Inhibitors
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DOI：
10.1002/anie.201208918
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发表时间：
2013-01-01
影响因子：
16.6
通讯作者：
Arai, Midori A.
中科院分区：
文献类型：
--
作者：
Arai, Takayoshi;Yamamoto, Yushi;Arai, Midori A.
吲哚类生物碱具有重要的生物活性，是药学领域的重要化合物在大量的吲哚中，两个吲哚在c3和c30位相连的分子代表了一个独特的双吲哚族在六氢吡罗吲哚类生物碱的全合成中，通过两个手性吲哚的自由基偶联，实现了二聚体3,3k -双吲哚的构建Kanai， Matsunaga等人报道了由氧吲哚和isatin缩合而成的双氧吲哚催化不对称双Michael反应合成了chimonantine和folicanthine然而，在开发更多样化的不对称双吲哚时，由于单个分子中两个吲哚基团的反应性难以控制，双吲哚骨架构建后的化学选择性转化是不利的。Overman[8]和Trost[9]课课组报道了由外消旋不对称的3-吲哚- 30 -基氧基吲哚与异丁苷衍生重氮化合物通过铑催化偶联反应合成(+)-gliocladin C的立体选择性全合成。Stephenson和他的同事开发了一种有趣的可见光光氧化还原催化吡咯啉与吲哚的不对称偶联，用于(+)-gliocladin C.[10]的全合成这些开创性的工作表明，具有不同氧化态的两种吲哚底物的偶联反应可能是一种替代的更简洁的方法
Indole alkaloids possess significant biological activity, and are important compounds in pharmaceutical science.[1] Among the large number of indoles, molecules in which two indoles are connected at the C3-and C3о-positions represent a unique family of bisindoles.[2] In addition to the staurosporines [3] and bisindolylmethanes,[4] directly connected bisindoles at the C3-and C3о-positions are also included in this category (Scheme 1).[5]In the total synthesis of hexahydropyrroloindoline alkaloids, the construction of dimeric 3, 3о-bisindoles has been achieved by the radical coupling of two chiral indoles.[6] Kanai, Matsunaga, and co-workers reported the total syntheses of chimonantine and folicanthine by a catalytic asymmetric double Michael reaction of bisoxindole, which was prepared by condensation of oxindole and isatin.[7] However, in the development of more diverse unsymmetrical bisindoles, chemoselective transformation after the construction of the bisindole skeletons is disadvantageous because the reactivity of two indole moieties in a single molecule is difficult to control. The research groups of Overman [8] and Trost [9] reported the stereoselective total synthesis of (+)-gliocladin C from racemic, unsymmetrical 3-indol-3о-yloxindoles, synthesized by a Rh-catalyzed coupling reaction of indoles with an isatin-derived diazo compound. Stephenson and co-workers developed an interesting visible-light photoredox catalytic unsymmetrical coupling of pyrroloindolines with indoles for the total synthesis of (+)-gliocladin C.[10] These pioneering works suggest that the coupling reaction of two indole substrates having different oxidation states could be an alternative and more concise approach for