Synthetic Studies of Polycyclic Natural Product Stemofoline and Its SAR Study

Stemofoline被称为乙酰胆碱酯酶抑制剂，因此它被认为是治疗阿尔茨海默病的有效药物。目前进行的构效关系研究表明，分子的整体结构对乙酰胆碱酯酶抑制活性有重要影响。我们开始了对这种分子的合成研究，试图合成各种茎麻碱衍生物，这些衍生物无法通过采用天然产物降解的半合成方法获得。因此，通过分子内1,3-偶极环加成和分子内sila-Pummerer反应的结合，以前所未有的环化模式构建了stemofoline的中心多环结构。

Stemofoline is known as a Acetylcholine esterase inhibitor, and thus it is known as the potent cure for Alzheimer disease. Structure-activity relationship study performed thus far indicated that the whole structure of the molecule is important for the Acetylcholine esterase inhibition activity. We started our synthetic study for this molecule in an attempt to synthesize various derivatives of stemofolines that could not be accessed by the semisynthetic approach employing the degradate of the natural product. As a result, construction of the central polycyclic structure of stemofoline was achieved by the combination of the intramolecular 1,3-dipolar cycloaddition and intramolecular sila-Pummerer reaction, with an unprecedented mode of cyclization.