Total Synthesis of Gukulenin A

综上所述，我们设想完成从gukulenins天然产物家族中首次完全合成海洋双（tropolonoid）四萜类化合物。gukulenins是从红色海绵Phorbas Gukulensis样品中分离出来的。gukulenins已被证明对体内和体外的各种癌细胞系具有强效的细胞毒性（gukulenin A）。迄今为止分离的8个gukulenins中有7个具有独特的六环双（α-tropolonoid）分子结构，具有十个手性中心和一个手性轴。到目前为止，gukulenins的结构解析是基于核磁共振实验的解释，并将通过我们的gukulenin A的全合成来验证。我们对gukulenin A全合成的动机首先源于天然产物的独特分子结构。由于靶分子结构前所未有，gukulenin A的全合成需要创新的合成方法。随着德梅奥反应的进一步发展，我们已经在第一个筹资期间在这方面作出了明显的贡献。在第二个资助期，进一步的合成方法发展也是必不可少的，特别是关于α-对偶酮的化学反应。如果我们的项目成功，我们将能够支持对gukulenins生物活性的进一步研究，尽管海洋海绵的可用性有限。

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.