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

聚酮类化合物因其高度的结构多样性和复杂性以及广泛的重要生物功能而成为极具吸引力的合成靶标。本研究项目的目的是开发新的方法，与已知的方法相比，更直接和更有效的方法，通过新的顺序过程合成多酮，允许通过一锅式结合几个合成转化来快速增加结构复杂性。这些方法允许有效地获得结构独特的多酮类化合物，包括粘菌来源的立体化学复杂和生物活性代谢物。计划首次合成这类天然产物的母体代表，并明确确定其确切的三维结构，并能够进一步评估这些稀有天然产物的不同寻常的生物学特征。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被追求，以发现新的和普遍有用的化学方法。

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.