Total synthesis of salvinorin A

该项目的主要目标是使用分子内Diels-Alder反应（IMDA）作为关键转化完成新克罗烷二萜salvinorin A的全合成。作为选择性κ-阿片受体（KOR）激动剂，鼠尾草素A代表了用于开发用于治疗中枢神经系统病症的新药剂的有吸引力的先导结构。我们的概念新颖的合成的完成将提供一个缩短的访问，这种新克罗烷相比，公开的总合成，并另外打开新的途径，结构类似物，这是不可用的，或只有困难，从天然产物。在这个研究项目的前期工作中，我们已经开发了一种用于新克罗烷BC子系统的双环结构单元的短路线。由于它的氧化烯烃裂解已经实现，它现在可以迅速转化为所需的三烯的关键的分子内[4+2]环加成，得到新克罗烷框架。在建立用于将该高级中间体转化为二萜鼠尾草素A的适当条件之后，还将检查我们的新克罗烷BC结构单元向与鼠尾草素A相关的生物活性二萜雀花黄素和科伦宾的简明转化。

The main objective of this project is the completion of the total synthesis of the neoclerodane diterpene salvinorin A using an intramolecular Diels-Alder reaction (IMDA) as the key transformation. As a selective kappa-opioid receptor (KOR) agonist, salvinorin A represents an attractive lead structure for the development of new agents for the treatment of disorders of the central nervous system. The completion of our conceptually novel synthesis would provide a shortened access to this neoclerodane compared to the published total syntheses and additionally open new avenues to structural analogs, which are not available, or only with difficulty, from the natural product. In previous work on this research project, we have developed a short route to a bicyclic building block for the neoclerodane BC subsystem. Since its oxidative olefin cleavage was already achieved, it can now be transformed rapidly into the desired triene for the crucial intramolecular [4+2] cycloaddition to give the neoclerodane framework. Next to establishing appropriate conditions for the conversion of this advanced intermediate into the diterpene salvinorin A, a concise transformation of our neoclerodane BC building block into the bioactive diterpenes chasmanthin and columbin related to salvinorin A is to be examined as well.