Total synthesis of jerangolides

Jerangolides是粘杆菌Sorangium cellulosum的次级代谢物。这些天然产物具有抗真菌活性。最近，Pharmazeutische biotechnology， Universität des Saarlandes的Rolf m<e:1> ller教授小组发现，jerangolides是粘球菌（Myxococcus xanthus）多细胞子实体生成的高效抑制剂。粘球菌是粘球菌亚目的另一种粘细菌。为了详细研究其药理活性，需要大量的桔梗内酯及其带有亲和标签的衍生物。因此，我们希望开发所有已知的jerangolides的全合成方法。基于这些天然产物的局部对称性，这些合成可以设计得非常短和有效（仅为已发表的合成选定jerangolides的一半步骤）。值得注意的是，我们的合成计划允许用相同的策略合成所有的jerangolides。合成了定义明确的jerangolides B、E和H的立体异构体，为确定手性未知的立体中心构型提供了可能性。此外，利用我们的策略，我们可以很容易地合成许多类似物，以进一步阐明构效关系。

Jerangolides are scundary metabolites from the myxobacterium Sorangium cellulosum. These natural products show antifungal activity. Recently, the group of Prof. Rolf Müller, Pharmazeutische Biotechnologie, Universität des Saarlandes, found that the jerangolides are highly potent inhibitors of the generation of multi-cell fruiting bodies of Myxococcus xanthus, another myxobacterium from the suborder Myxococcales. To study this pharmacological activity in detail, large amounts of the jerangolides as well as derivatives thereof with affinity tags are required. Therefore, we want to develop total syntheses of all known jerangolides. Based on a local symmetry in these natural products, these syntheses can be designed very short and efficient (only half the number of steps of already published syntheses of selected jerangolides). Notably, our synthetic plan allows the synthesis of all jerangolides with the same strategy. The synthesis of well-defined stereo isomers of the jerangolides B, E and H offers the possibility to determine the configuration of a stereocenter with unknown chirality. Furthermore, with our strategy we can easily synthesize numerous analogues to additionally elucidate structure-activity relationships.