权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

First expedient syntheses of naturally occuring protoilludane type sesquiterpenes and analogues; Application of innovative and unprecedented routes for the formation of cyclobutenes, alkylidenecyclobutanes and unsaturated four-membered heterocycles

天然存在的原伊鲁烷型倍半萜及其类似物的首次便捷合成；

基本信息

批准号：
357443029
负责人：
Professor Dr. Dorian Didier
金额：
--
依托单位：
Arbeitsgruppe Organische Chemie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2017
资助国家：
德国
起止时间：
2016-12-31 至 2019-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/357443029?language=en
关键词：
First expedient syntheses naturally occuring

项目摘要

Unsaturated four-membered ring systems are important synthons in synthetic organic chemistry. However, a lack of diverse and available methodologies limit the current scope for possible studies. Through innovative and unprecedented strategies, we wish to develop a new toolbox that would simplify access and sophistication of such architectures. We already demonstrated the great potential of one-pot sequences to undergo the diastereo- and enantioselective formation of alkylidenecyclobutanes by combining boron-homologation and boron-allylation reactions. In order to develop rapid and diversified syntheses of four-membered ring derivatives, we will take on the challenge of introducing heteroelements to the core of cyclic structures. As four-membered heterocycles have been recognized as important patterns in drug discovery, novel and straightforward methods towards their construction will represent highly valuable tools in organic and medicinal chemistry. Azete, oxete and thiete will be obtained via new synthetic methods and further derivatized into alkylidene four-membered heterocyclic molecules, employing either boron-allylations or gamma-selective cross-coupling reactions. In addition, their functionalization will be explored to open a landscape of entirely new substrates for further studies. The obtained vinyl-cyclobutenes, -azetes, -oxetes and -thietes will be taken to the next level of molecular architectures by developing stereo- and regioselective Diels-Alder reactions, to furnish complex fused ring systems. In parallel, efforts will be made to apply these unique one-pot sequences to the synthesis of naturally occurring sesquiterpenoids of the protoilludane class, which present interesting biological properties. Expedient and stereoselective routes have been designed to access such 4-6-5 fused cyclic systems, based on the methodologies that we have previously established, and these would allow for a wide diversification of the different scaffolds, starting from common intermediates. In collaboration with the pharmaceutical department, surrogates will be evaluated for their antibacterial and antifungal properties to ultimately lead to great improvements in medicinal chemistry on this specific class of compounds, the synthesis of which has scarcely been explored.

不饱和四元环系是合成有机化学中的重要化合物。然而，由于缺乏多样化和可用的方法，限制了目前可能进行研究的范围。通过创新和前所未有的策略，我们希望开发一个新的工具箱，以简化此类体系结构的访问和复杂性。我们已经证明了单锅序列通过结合硼同源化和硼烯丙化反应进行非映对和对映选择性形成烷基烷环丁烷的巨大潜力。为了发展快速、多样化的四元环衍生物的合成，我们将在环结构的核心引入杂元素。由于四元杂环已被公认为药物发现的重要模式，新的和直接的方法来构建它们将是有机化学和药物化学中非常有价值的工具。Azete， oxete和thite将通过新的合成方法得到，并通过硼烯化反应或γ选择性交叉偶联反应进一步衍生成烷基烷四元杂环分子。此外，它们的功能化将被探索，为进一步研究开辟一个全新的底物景观。所获得的乙烯基环丁烯、-氮、-氧和-硫将通过发展立体和区域选择性diols - alder反应而进入分子结构的下一个水平，以提供复杂的融合环体系。同时，将努力将这些独特的一锅序列应用于天然存在的原酰苯环类倍半萜类化合物的合成，这些化合物具有有趣的生物学特性。基于我们之前建立的方法，我们设计了方便和立体选择性的途径来获得这种4-6-5融合循环系统，这些途径将允许从常见中间体开始的不同支架的广泛多样化。与制药部门合作，将评估替代品的抗菌和抗真菌性能，最终导致这类化合物的药物化学的巨大改进，其合成几乎没有探索过。