异小构树碱及其类似物的合成.pdf

摘 要 多羟基吡咯烷类生物碱是一类重要的亚氨基糖，其独特的分子结构和对 糖苷酶潜在的抑制活性引起了人们广泛的关注。对于这一类亚氨基糖的结构 修饰是设计合成具有更高生物活性亚氨基糖的重要方式。小构树碱W 是一种 具有较好的 β- 糖苷酶抑制活性的亚氨基糖，本论文设计合成了 iso- Broussonetine W 以及一系列具有相同的13 碳原子支链的衍生物。 一．iso-Broussonetine W 的合成 我们从商业易得的双丙叉葡萄糖出发，通过15 步转化得到中间体酮2- 199，再通过格氏加成反应得到侧链加成产物 2-210。我们尝试了通过烯烃 复分解、Suzuki 反应、不饱和羰基加成反应等方法对目标产物进行合成，但 是都没有成功。 二．iso-Broussonetine W 衍生物的合成 我们通过侧链加成的中间体2-199，利用烯烃复分解反应进行了一系列 C-2 枝化衍生物的合成，对于这一类的枝化衍生物的系统合成和生物活性测 试对于研究此类化合物的构效关系有至关重要的作用。 I 异小构树碱W 及其类似物的合成 关键词：异小构树碱W C-2 枝化 亚氨基糖 II Abstract Polyhydroxylated pyrrolidine alkaloids are an important family of iminosaccharides. They have attracted widespread attention due to their unique molecular structure and potential glycosidase inhibition activity. The structural modification of such iminosaccharides is an important way to access iminosaccharides with higher biological activity. In this dissertation, the C-2 migrated analogues of broussonetine W and a series of C13 branched derivatives were synthesized. 1. Synthesis of iso-Broussonetine W The intermediate ketone 2-199 was prepared from commercially available diacetone-d-glucose in 15 steps, using Grignard reaction to produce 2-210. We tried to synthesize the target compound by olefin metathesis, Suzuki reaction, unsaturated carbonyl addition reaction, etc., but unfortunately all failed. 2. Synthesis of iso-Broussonetine W Derivatives A series of C-2 branched derivatives were synthesized from 2-199, using Grignard reaction and cross metathesis as key steps.