Synthesis and Neurotrophic Activity Studies of Illicium Sesquiterpene Natural Product Analogues.
Synthesis and Neurotrophic Activity Studies of Illicium Sesquiterpene Natural Product Analogues.
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DOI：
10.1002/chem.201605362
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发表时间：
2017-03
期刊：
影响因子：
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通讯作者：
Johannes Richers;A. Pöthig;E. Herdtweck;C. Sippel;F. Hausch;K. Tiefenbacher
中科院分区：
文献类型：
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作者：
Johannes Richers;A. Pöthig;E. Herdtweck;C. Sippel;F. Hausch;K. Tiefenbacher
神经营养性天然产物具有开发抗神经变性治疗剂的特权结构的潜力。然而，只有少数研究已经进行了调查一个共同的药效基序和结构活性关系（SAR）。在这里，调查结构上更简单的类似物的神经营养倍半萜的八角家庭。简明的合成路线使得能够以克级制备（±）-Merrilactone A和（±）-Anislactone A/B的碳骨架。这允许通过修改核心结构，包括氧化水平的变化和官能团的改变来获得一系列结构类似物。总共合成了15种天然产物的衍生物，并测试了它们的神经突生长活性。我们的研究表明，结构更简单的天然产物类似物可以保留有希望的生物活性，这些类似物可以通过简单的合成路线获得。
Neurotrophic natural products hold potential as privileged structures for the development of therapeutic agents against neurodegeneration. However, only a few studies have been conducted to investigate a common pharmacophoric motif and structure-activity relationships (SARs). Here, an investigation of structurally more simple analogues of neurotrophic sesquiterpenes of the illicium family is presented. A concise synthetic route enables preparation of the carbon framework of (±)-Merrilactone A and (±)-Anislactone A/B on a gram scale. This has allowed access to a series of structural analogues by modification of the core structure, including variation of oxidation levels and alteration of functional groups. In total, 15 derivatives of the natural products have been synthesized and tested for their neurite outgrowth activities. Our studies indicate that the promising biological activity can be retained by structurally simpler natural product analogues, which are accessible by a straightforward synthetic route.