环状海星皂甙Sepositoside A的合成研究

Starfish glycoside is an important class of marine natural products and they possess a broad spectrum of bioactivities and manifold architectural complexity. Structurally, these molecules can be roughly divided into three categories, i.e., sulfated starfish glycosides, polyhydroxylated starfish glycosides and cyclic starfish glycosides. So far, several starfish glycosides have been synthesized, but none of cyclic starfish glycosides were included because of the extremely challenging 16-membered large ring. In this project, we selected sepositoside A, a typical cyclic starfish glycoside, as the target molecule, hoping to establish a modular synthetic approach to this compound as well as its analogues and thus enable in-depth study on their structure-activity relationships.. We plan to construct an expanded large ring via macrolactonization and then achieve ring contraction by acid-promoted formation of glucopyranosyl unit, thus furnishing the strained 16-membered large ring in target molecule. As the aglycone part is labile to acids and 3β-OH is a relatively inactive acceptor, we intend to harness the recent developments in glycosylation including the mild Au(I)-catalyzed protocol to install needed monosaccharide units.

海星皂甙是一类重要的海洋天然产物，具有丰富的生物活性和多样的结构特点。从结构上来看，海星皂甙可以分为三种类型，即硫酸化海星皂甙、多羟基海星皂甙和环状海星皂甙。目前，硫酸化海星皂甙和多羟基海星皂甙均有合成报道的例子，而环状海星皂甙由于其分子内的大环结构带来的挑战，尚无相关合成报道。本项目中，我们选取Sepositoside A为合成研究的目标分子，期望发展出一种模块化的合成路线，同时合成若干类似物并进行构效关系研究。. 我们拟采用大环内酯化反应来进行关环，通过酸促进的吡喃糖环构建实现缩环操作，从而实现目标分子中极具挑战性的张力大环结构。考虑到甙元部分对酸的敏感性及其在糖苷化反应中的低活性，我们计划尝试新近发展的温和高效的金催化糖苷化方法，以期实现相关单糖片段的安装。

海星皂甙是一类重要的海洋天然产物，具有丰富的生物活性和多样的结构特点。从结构上看，海星皂甙可以分为三大类，既海星皂甙、多羟基海星皂甙和环状海星皂甙。其中，环状海星皂甙具有十分独特的16员张力大环结构，在合成上颇具挑战。本项目通过全合成手段合成了典型的环状海星皂甙Sepositoside A，为后续的构效关系和作用机制研究铺平了道路。.本项目从麦角固醇、全乙酰基葡萄糖、全乙酰基半乳糖、L-阿拉伯糖等商品化试剂出发，快速构建了所需四个砌块。随后，利用烯烃复分解和不对称双羟化构建了立体拥挤的甙元-葡萄糖间醚键；通过TrBArF4促进的N-苯基三氟乙亚胺酯给体和HOTf促进的三氯乙酰亚胺酯给体的糖苷化构建了甾环C3的二糖片段；通过Au(I)催化的关环糖苷化反应构建了关键的16员大环结构。最后，通过不对称双羟化和保护基操作顺利实现了天然产物Sepositoside A的首次全合成。本项目开发的合成路线高度模块化，对其他环状糖类化合物和复杂糖缀合物的合成也将发挥启发作用。