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Natural products as a rich source of pharmaceuticals and innovative chemical transformations: platform development for the generation of new antiviral drugs, antifeedant terpenoids, and novel methodology for chemical synthesis

天然产物作为丰富的药物来源和创新的化学转化：用于生成新型抗病毒药物、拒食萜类化合物的平台开发以及化学合成的新方法

基本信息

批准号：
244325724
负责人：
Professor Dr. Thomas Magauer
金额：
--
依托单位：
Institut für Organische Chemie
依托单位国家：
德国
项目类别：
Independent Junior Research Groups
财政年份：
2013
资助国家：
德国
起止时间：
2012-12-31 至 2017-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/244325724?language=en
关键词：
Natural products rich source pharmaceuticals

项目摘要

Natural products are a rich source for novel biologically active molecules. They have been inspiring scientists for more than a century and have entailed seminal discoveries in the natural sciences. The unique biological spectrum and the complex molecular framework they often display lead to intriguing research projects that offer new ideas for chemical transformations and important biological insights. This proposal covers three such projects. First, we present a bio-inspired strategy for the synthesis of much-needed, potent antiinfluenza A compounds. Two highly active members of this class are the polycyclic meroterpenoids stachyflin and aureol, which display a novel mode of action. Our general and convergent synthetic route not only provides one individual member of this class but also gives direct access to related natural products, allows for rapid diversification, and can produce a library of novel analogs not yet accessible via semi-synthesis. Second, a biomimetic enantioselective decarboxylative protonation (EDP) protocol of 2- hydroxymalonates is developed and applied for the synthesis of the recently discovered, antifeedant leucosceptroid sesterterpenoids. The biosynthesis of the leucosceptroids is unknown and the planned biomimetic conversion of leucosceptroid A and B to C and D will shed light on part of it. Finally, the third part is dedicated to the synthesis of halogenated molecules, which are highly versatile and valuable building blocks in medicinal chemistry. The one-pot beta-halogenation of unsaturated compounds and a reductive ring expansion of gem-dihalocyclopropanes are described and applied for the synthesis of two indole alkaloids, the acetylcholinesterase (AChE) inhibitors kopsihainanines A and B.

天然产物是新型生物活性分子的丰富来源。世纪以来，它们一直激励着科学家，并在自然科学领域带来了开创性的发现。独特的生物光谱和它们经常显示的复杂分子框架导致了有趣的研究项目，为化学转化和重要的生物学见解提供了新的思路。本提案涉及三个此类项目。首先，我们提出了一种生物启发的策略，用于合成急需的，有效的抗流感A化合物。这一类的两个高度活跃的成员是多环meroterpenoids stachyflin和aureol，它们显示了一种新的作用模式。我们的一般和收敛的合成路线不仅提供了这类的一个单独的成员，而且还提供了直接获得相关的天然产物，允许快速多样化，并可以产生一个新的类似物库尚未通过半合成。其次，仿生对映选择性脱羧质子化（EDP）协议的2-羟基丙二酸酯的开发和应用于最近发现的，拒食的leucoseptroid二萜类化合物的合成。的leucoseptroids的生物合成是未知的和拟仿生转换leucoseptroids A和B到C和D将揭示了它的一部分。最后，第三部分是致力于卤代分子的合成，这是高度通用的和有价值的积木在药物化学。本文报道了不饱和化合物的一锅法β-卤代反应和偕二卤代环丙烷的还原性扩环反应，并应用于合成两种吲哚生物碱--乙酰胆碱酯酶（AChE）抑制剂kopsihainanines A和B。