以轴手性联芳为关键合成子对三环反式手性二醇类天然产物的高效构建

Tricyclic chiral trans-diol structure is an important structural unit, which widely exists in drugs and natural products. These natural products have important biological activities such as anti-angiogenesis, anti-aromatase activity and anti-fungal activity. Their unique structure and excellent biological activity have attracted much attention in the synthesis of these natural molecules. Therefore, the development of simple and efficient synthetic methods is of great significance for the universal synthesis of such natural products. In this project, we aim to develop an efficient and universal method to synthesize TAN-1085, FD-594, Pradimicinone and their analogues and derivatives using Suzuki coupling, asymmetric C-H functionalization, olefin oxidation, axially chiral to central chiral transfer as key steps.

三环手性反式二醇结构是一类重要的结构单元，广泛存在于药物及天然产物之中。这类天然产物具有抗血管增生、抗芳香酶活性、抗真菌等重要的生理活性，其独特的结构和优异的生理活性使得该系列天然分子的全合成备受关注。因此，发展简洁高效的合成方法，对该类天然产物进行普适性地合成具有重要意义。在该项目中，我们拟将轴手性联芳作为关键合成子，发展一个高效普适性的方法即以Suzuki偶联、不对称碳氢官能团化、烯烃氧化、轴手性到中心手性转移为关键合成步骤，实现三环手性反式二醇类天然产物TAN-1085、FD-594、Pradimicinone的全合成及其类似物和衍生物的简洁、高效、集群式合成。

通过该项目，在我们发展了高效不对称碳氢键活化构建轴手性联芳的体系，实现了轴手性联芳木脂素（steganone, isoschizandrin）、三环反式二醇（TAN-1085）等天然产物的全合成或形式全合成。在此工作基础之上，发展了两种不同的催化体系实现了对单轴、多轴化合物的高立体选择性合成，包括利用“瞬态手性辅基”策略合成联芳轴手性醛化合物，以及Pd(II)/手性磷酸(CPA)催化体系构建硫醚或硒醚联芳基轴手性化合物。