Total Synthesis of Gukulenin A

Gukulenin A 的全合成

• 批准号: 344336255
• 负责人: Professor Dr. Martin Hiersemann
• 金额: --
• 依托单位: Forschungsgebiet Organische Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/344336255?language=en
• 关键词: Total; Synthesis; Gukulenin

In summary, we envision the completion of the first total synthesis of a marine bis(tropolonoid) tetraterpenoid from the natural product family of the gukulenins. The gukulenins are isolated from samples of the red marine sponge Phorbas Gukulensis. The gukulenins have been shown to be potent cytotoxics for various cancer cell lines in vivo and in vitro (gukulenin A). Seven of the eight gukulenins isolated to date exhibit a unique hexacyclic bis(α-tropolonoid) molecular architecture with ten centers of chirality and one axis of chirality. The structural elucidation of gukulenins has so far been based on the interpretation of NMR experiments and will be verified by our total synthesis of gukulenin A. Our motivation for the total synthesis of gukulenin A stems first from the unique molecular architecture of the natural product. Total synthesis of gukulenin A requires innovative synthesis method development due to the unprecedented target molecule architecture. With the further development of the de Mayo reaction, we have already made a visible contribution in this respect during the first funding period. Further synthesis method development is also essential in the second funding period, especially with regard to chemistry with and on α-tropolones. If our project is successful, we will be able to support further studies on the biological activity of gukulenins despite limited availability from the marine sponge.

总之，我们设想完成来自 gukulenins 天然产物家族的海洋双（tropolonoid）四萜类化合物的首次全合成。gukulenins 是从红色海洋海绵 Phorbas Gukulensis 的样品中分离出来的。在体内和体外对各种癌细胞系具有有效的细胞毒性（gukulenin A），迄今为止分离的八种 gukulenin 中的 7 种表现出独特的六环。具有十个手性中心和一个手性轴的双（α-tropolonoid）分子结构迄今为止是基于 NMR 实验的解释，并将通过我们的 gukulenin A 的全合成来验证。古库列宁A的全合成首先源于天然产物独特的分子结构，由于前所未有的目标分子结构，古库列宁A的全合成需要创新的合成方法开发。 de Mayo 反应，我们在第一个资助期内已经在这方面做出了明显的贡献，在第二个资助期中，进一步的合成方法开发也至关重要，特别是在 α-托酚酮的化学方面，如果我们的项目成功的话。尽管海绵的供应有限，但我们将能够支持对古库列宁生物活性的进一步研究。