Development of a Highly Modular Synthesis of the Novel Anti-Influenza Natural Products Wickerol A and B

新型抗流感天然产物 Wickerol A 和 B 的高度模块化合成的开发

• 批准号: 329049264
• 负责人: Dr. Matthias Göhl
• 金额: --
• 依托单位: Department of Chemistry
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/329049264?language=en
• 关键词: Development; Highly; Modular; Synthesis; Novel

There is neither a total synthesis of the potent antiviral wickerols A and B, nor of suitable model systems known to date. As these structures are very promising potential pharmacophores for further anti-influenza structure activity relationships investigations, we would like to develop a synthetic approach to access this kind of compounds in this project. As both interesting diterpenes have a novel fused 6-5-6-6 complex cage structure, they seem challenging to prepare. The key transformations include a [2,3]-Wittig anionic oxy-Cope rearrangement cascade followed by a type II ring-closing carbonyl-ene reaction to establish the last axial-faced carbocycle with functionalizations in the right place. Essentially, our main focus is to outline short synthetic strategy that is highly modular and allows late-stage diversification for promising SAR studies.

既没有强效抗病毒的柳条醇a和B的完全合成，也没有迄今为止已知的合适的模型系统。由于这些结构在进一步的抗流感结构活性关系研究中是非常有前景的潜在药效团，我们希望在本项目中开发一种合成方法来获取这类化合物。由于这两种有趣的二萜都具有新颖的融合6-5-6-6复杂的笼状结构，因此它们的制备似乎具有挑战性。关键的转化包括[2,3]-Wittig阴离子氧- cope重排级联，然后是II型闭环羰基-烯反应，以在正确的位置建立具有官能化的最后一个轴面碳环。从本质上讲，我们的主要重点是概述高度模块化的短期综合策略，并允许有前途的SAR研究的后期多样化。