Core-Structure-Oriented Asymmetric Organocatalytic Substitution of 3-Hydroxyoxindoles: Application in the Enantioselective Total Synthesis of (+)-Folicanthine
Core-Structure-Oriented Asymmetric Organocatalytic Substitution of 3-Hydroxyoxindoles: Application in the Enantioselective Total Synthesis of (+)-Folicanthine
复制标题
3-羟基吲哚的核心结构导向不对称有机催化取代：在( )-叶棘素对映选择性全合成中的应用
DOI：
10.1002/anie.201107079
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发表时间：
2012-01-01
影响因子：
16.6
通讯作者：
Gong, Liu-Zhu
中科院分区：
文献类型：
--
作者：
Guo, Chang;Song, Jin;Gong, Liu-Zhu
环色胺生物碱构成了一个天然产物大家族（图1），它们显示出令人着迷的生物活性。 [1]例如，(+)-毛壳素不仅具有抗菌和细胞抑制活性，而且还是赖氨酸特异性组蛋白甲基转移酶的有效抑制剂。 [2]化合物 WIN 64821 首次从曲霉属物种中分离出来，[3] 是一种针对人神经激肽-1 和胆囊收缩素 B 受体的有效竞争性 P 物质拮抗剂。 [4]此外，环色胺生物碱家族的其他成员也被发现表现出重要的生物和药物活性。 [5]除了广泛的生物活性外，环色胺生物碱还含有八氢-3a, 3'abispyrrolo [2, 3-b] 吲哚亚基（核心结构 A，图 1），其特征是邻近的全碳四级立构中心。这些化合物一直是有机合成领域的长期挑战。[6]这些生物碱所表现出的独特的结构阵列和有趣的生物活性导致了对有效的不对称合成方法的需求。世界各地的研究小组致力于开发新的合成方法来构建六氢吡咯并吲哚骨架。 [7] Overman 及其同事报道了光学纯的蜡菊酯的对映选择性全合成，其中利用分子内双 Heck 和二烷基化反应构建环色胺核心，立体化学控制来自酒石酸衍生物。 [8] Movassaghi 及其同事建立了 3-溴-六氢吡咯并吲哚的还原同二聚体，很容易衍生自 L-色氨酸，这提供了邻近四元立体中心的简便构建，从而导致了几种光学纯环色胺生物碱的对映选择性全合成。 [9]最近，Sodeoka 和同事将相关策略应用于 (+)-毛壳素的全合成。 [10]此外，Overman 及其同事描述了从核心结构 A 的内消旋衍生物开始的催化剂控制的对映选择性全合成环色胺生物碱。 [7, 11] 尽管取得了这些出色的成就，但开发获取 A 型环色胺结构的对映选择性催化方法在六氢吡咯并吲哚生物碱家族的全合成中仍然具有重要意义。在过去的几年中，人们为全碳季3, 3'-二取代羟吲哚的对映选择性合成做出了许多努力，[12]，但这些方案尚未提供用于合成3a, 3a'-双吡咯烷[2, 3-b]二氢吲哚骨架的手性中间体。这种催化对映选择性合成尚未解决的挑战促使我们考虑一种新方法。正如方案 1 中的逆合成分析所示，我们合成核心结构 A 的策略涉及通过 Rodrigo 方案从二酰胺 1 获取 A 型结构。 [13]二酰胺1可以通过氧化/烷基化反应由2制备。贝克曼重排反应将从3得到2，它被认为是合成核心结构A的关键中间体，可以通过对映选择性取代获得
Cyclotryptamine alkaloids constitute a large family of natural products (Figure 1) which show fascinating biological activities.[1] For example,(+)-chaetocin not only shows antibacterial and cytostatic activity, but is also a potent inhibitor of a lysine-specific histone methyltransferase.[2] The compound WIN 64821, first isolated from Aspergillus sp.,[3] is a potent competitive substance P antagonist with respect to human neurokinin-1 and the cholecystokininB receptor.[4] Moreover, other members of the cyclotryptamine alkaloid family have also been found to exhibit important biological and pharmaceutical activities.[5] In addition to their wide range of bioactivities, the cyclotryptamine alkaloids contain an octahydro-3a, 3’abispyrrolo [2, 3-b] indole subunit (core structure A, Figure 1), which is characterized by vicinal all-carbon quaternary stereogenic centers. These compounds have been a longstanding challenge in organic synthesis.[6] The unique structural arrays and interesting biological activities displayed by these alkaloids have led to a demand for efficient asymmetric synthetic methods. Much effort has been directed toward the development of new synthetic methods for the construction of hexahydropyrroloindole skeletons from research groups around the world.[7] Overman and co-workers reported the enantioselective total synthesis of optically pure chimonanthines, wherein intramolecular double Heck and dialkylation reactions were exploited to construct the cyclotryptamine core, and the stereochemical control came from a tartrate derivative.[8] Movassaghi and co-workers have established a reductive homodimerization of 3-bromo-hexahydropyrroloindole, readily derived from L-tryptophan, which provided facile construction of the vicinal quaternary stereogenic centers that led to the enantioselective total synthesis of several optically pure cyclotryptamine alkaloids.[9] Very recently, Sodeoka and co-workers applied a related strategy to the total synthesis of (+)-chaetocin.[10] In addition, Overman and co-workers have described the catalyst-controlled enantioselective total syntheses of cyclotryptamine alkaloids from meso derivates of the core structure A.[7, 11] In spite of these elegant achievements, the development of an enantioselective catalytic method to access cyclotryptamine structures of type A still holds great importance in the total synthesis of the hexahydropyrroloindole alkaloid family. Over the past several years, numerous endeavors have been directed toward the enantioselective synthesis of allcarbon quaternary 3, 3’-disubstituted oxindoles,[12] but these protocols have not provided a chiral intermediate for the synthesis of the 3a, 3a’-bispyrrolidino [2, 3-b] indoline skeleton. The unmet challenge of this catalytic enantioselective synthesis prompted us to consider a new approach. Our strategy to synthesize the core structure A, as indicated by the retrosynthetic analysis in Scheme 1, involves accessing structures of type A from diamide 1 by the Rodrigo protocol.[13] The diamide 1 would be prepared from 2 through oxidation/alkylation reactions. A Beckmann rearrangement reaction would give 2 from 3, which is considered to be the key intermediate for the synthesis of the core structure A, and could be obtained from an enantioselective substitution