Novel sequential and biomimetic methods for polyketides: Total synthesis of Tuscolid/Tuscoron

聚酮类化合物由于其高度的结构多样性和复杂性以及广泛的重要生物学功能而成为具有吸引力的合成靶点。本研究项目的目的是开发新颖的-与已知程序相比，更直接和有效的-通过新颖的顺序过程合成聚酮的方法，这种方法允许通过在一锅方式中结合几种合成转换从简单的构建块快速增加结构复杂性。这些方法允许有效地接近结构独特的聚酮tuscolid和tuscorones，立体化学复合物和黏菌起源的生物活性代谢物。计划首次合成这类天然产物的亲本代表，明确确定其确切的三维结构，并进一步评估这些稀缺天然产物的不寻常生物学特征。最后，在他们极不寻常的生物合成的激励下，冒险的仿生合成方法将随着发现新颖和普遍有用的化学方法的概念而被追求。

Polyketides are attractive synthetic targets due to high degrees of structural diversity and complexity in combination with a broad range of important biological functions. Aim of this research project is the development of novel - in comparison to known procedures more direct and effective - methods to synthesize polyketides by novel sequential processes, which allow for a rapid increase of structural complexity from simple building blocks by combination of several synthetic transformations in a one-pot fashion.These methods allow for efficient approaches to the structurally unique polyketides tuscolid and tuscorones, stereochemically complex and biologically active metabolites of myxobacterial origin. It is planned to synthesize the parent representatives of this class of natural products for the first time, also to unequivocally determine their exact three-dimensional structures and to enable further evaluation of the unusual biological profiles of these scarce natural products. Finally, motivated by their highly unusual biosyntheses adventurous biomimetic synthetic approaches will be pursued with the notion to discover novel and generally useful chemical methods.