本项目是将含氟合成子的合成方法学与天然产物的合成结合起来，分子设计与合成含氟天然产物的类似物。该项目包含二方面的研究内容：首先探索出重要含氟合成砌块：γ,γ-二氟-α, β-不饱和δ内酯的合成方法学，将主要研究含二氟亚甲基的1,5-不饱和二醇一步氧化关环来构建这一重要含氟合成砌块。然后应用该砌块来合成具有生物活性的天然产物goniothalamin和pironetin的含氟类似物。同时也探索了具有重要抗癌活性的天然产物Fostriecin 和 Discodermolide二氟亚甲基类似物的合成。

Currently more than half of the prescription drugs are of natural product origin and the expectations from combinatorial libraries in drug screening have not been realized. Therefore, the natural product-inspired drug discovery and development has received renewed attention in recent years. The interest of fluorinated analogs of natural products is increasing continuously, because the incorporation of fluorine atom(s) or fluoroalkyl groups may greatly modify the chemical properties and biological activities of those molecules. In this project, an efficient and general strategy to gem-difluoromethylenated α, β-unsaturated δ-lactones in high yields from various aldehydes (including aliphatic, aromatic,α,β-unsaturated and sterically hindered aldehydes) has been developed. This methodology was successfully applied for the preparation of the natural products analogues containing gem-difluoromethylenated α,β-unsaturated δ-lactone moiety, such as gem-difluoromethylenated goniothalamin and pironetin. The synthesis of gem-difluoromethylenated fostriecin and discodermolide was also extensively investigated.

本项目是将含氟合成子的合成方法学与天然产物的合成结合起来，分子设计与合成含氟天然产物的类似物。该项目包含二方面的研究内容：首先探索出重要含氟合成砌块：γ,γ-二氟-α, β-不饱和δ内酯的合成方法学，将主要研究含二氟亚甲基的1,5-不饱和二醇一步氧化关环来构建这一重要含氟合成砌块。然后应用该砌块来合成具有生物活性的天然产物goniothalamin和pironetin的含氟类似物。同时也探索了具有重要抗癌活性的天然产物Fostriecin 和 Discodermolide二氟亚甲基类似物的合成。