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.

综上所述，我们预计将完成从古库兰素天然产物家族中首次全合成海洋双(对旋体)四萜类化合物。古库兰素是从红色海绵Phorbas Gukulensis的样品中分离得到的。古库兰素已被证明在体内和体外对各种癌细胞株(古库兰素A)具有很强的细胞毒作用。到目前为止分离的8个古古兰素中，有7个具有独特的六环双(α-tropolonid)分子结构，具有10个手性中心和1个手性轴。到目前为止，古库兰素的结构解释一直基于核磁共振实验的解释，并将通过我们的古库兰素A的全合成来验证。我们全合成古库兰素A的动机首先来自于天然产物独特的分子结构。古库兰素A的全合成需要创新的合成方法，因为它具有前所未有的目标分子结构。随着德马约反应的进一步发展，我们在第一个资助期已经在这方面做出了明显的贡献。在第二个资助期，进一步开发合成方法也是至关重要的，特别是在使用和使用α-tropolone的化学方面。如果我们的项目成功，我们将能够支持进一步研究古库兰素的生物活性，尽管从海绵中获得的数量有限。