Synthetic Studies of Polycyclic Natural Product Stemofoline and Its SAR Study

Stemofoline被称为乙酰胆碱酯酶抑制剂，因此它被称为阿尔茨海默病的有效治疗。结构-活性关系研究表明，分子的整体结构对乙酰胆碱酯酶抑制活性很重要。我们开始了对该分子的合成研究，试图合成stemofolines的各种衍生物，这些衍生物不能通过采用天然产物降解物的半合成方法获得。结果表明，通过分子内1，3-偶极环加成反应和分子内Sila-Pummerer反应的结合，以前所未有的环化方式构建了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.