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

迄今为止，既没有有效的抗病毒Wickerol A和B的全合成，也没有已知的合适的模型系统。由于这些结构是非常有前途的潜在药效团，进一步抗流感构效关系的研究，我们想在这个项目中开发一种合成方法来获得这类化合物。由于这两种有趣的二萜都具有新颖的稠合6-5-6-6复杂笼状结构，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，以建立最后一个轴向碳环，并在正确的位置进行官能化。从本质上讲，我们的主要重点是概述短的合成策略，是高度模块化，并允许后期多样化的有前途的SAR研究。

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.