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.

总而言之，我们设想完成了古库林蛋白天然产物家族的海洋双（Tropolonoid）四苯二苯二甲酸的首个总合成。古库林蛋白是从红船赞助商Phorbas Gukulensis的样品中分离出来的。古库烯蛋白已被证明是体内和体外各种癌细胞系的潜在细胞毒素（gukulenin a）。迄今为止分离的八种gukulenins中有七个表现出具有十个中心手性中心和一根手性轴的独特的六囊性双BIS（α-tropolonoid）分子结构。到目前为止，gukulenins的结构阐明是基于NMR实验的解释，并将通过我们对Gkulenin A的总合成来验证A。GkuleninA的总合成的动机首先源于自然产物的独特分子结构。 Gkulenin A的总合成需要由于前所未有的靶标构建而创新的合成方法开发。随着DE Mayo反应的进一步发展，我们已经在第一笔资金期间在这方面做出了明显的贡献。进一步的合成方法发展在第二个资金期间也是必不可少的，尤其是在与α-传统的化学方面。如果我们的项目成功，我们将能够支持有关gukulenins目的地生物学活动有限的进一步研究。