抗艾滋病天然产物Rubriflordilactione B的多样性导向合成

In this project, Rubriflordilactione B was studied on diversity-oriented synthesis as a lead compound,which was isolated from Schisandra rubriflora. .The natural product Rubriflordilactione B has not only the highly complex and novel multi-ring structure but also very important anti-aids biological activity. The convergent strategy was designed for synthesis of the Rubriflordilactione B. the feature of the route is organo catalysis and transition metal catalysts for efficient building the molecular skeleton and chiral center; Based on this route, the Rubriflordilactione B was diversity synthesis from the functional groups, constructing unit, stereochemistry and molecular skeleton diversity. As an example, the natural product Rubriflordilactione A was synthesis by using skeleton diversity strategies. .It is of great significance to study on the diversity-oriented synthesis of Rubriflordilactione B for the design and synthesis of new and complicated compounds as well as find efficiency and low poison of candidates.

本项目拟以中药红花五味子中分离得到的天然产物Rubriflordilactione B为先导化合物进行定向多样性合成研究。.Rubriflordilactione B不仅具有复杂、新颖的多环结构，而且具有重要的抗艾滋病生物活性，以该化合物作为先导化合物设计汇聚式合成路线，路线中大量采用现代合成方法，如有机小分子催化和过渡金属催化等来高效构筑分子骨架、手性中心和环系；并从官能团、构建单元、立体化学和分子骨架多样性上对先导化合物进行定向多样性合成，同时利用分子骨架多样性策略来合成源于同一物种的天然产物Rubriflordilactione A。.此研究对于丰富新化合物和复杂化合物多样性的设计与合成及寻找高效低毒的候选药物具有重要意义。

本项目以中药红花五味子中分离得到的天然产物Rubriflordilactione B为先导化合物进行定向多样性合成研究。天然产物Rubriflordilactone B不仅具有复杂、新颖的多环结构，而且具有重要的抗艾滋病生物活性，以该化合物作为先导化合物设计汇聚式合成路线，同时利用分子骨架多样性策略来合成源于同一物种的天然产物Rubriflordilactione A。. 依据计划书中的合成路线，以Mukaiyama-Michael加成和过渡金属催化的[2+2+2]三炔环化为关键反应，线性最长10步反应高效的合成了C-5-差向的Rubriflordilactone B的ABCDE环系；以Polar-radical-crossover cycloaddition (PRCC) 反应为关键反应，从商品易得的原料出发以四步反应高效简洁和立体选择性的合成带有五个手性中心的目标分子Rubriflordilactone B的右半部DEFG环系和骨架。为最后合成目标分子打下了基础。. 此研究对于丰富新化合物和复杂化合物多样性的设计与合成及寻找高效低毒的候选药物具有重要意义。