Total Synthesis of Gukulenin A

总之，我们设想完成的第一个全合成的海洋双（tropolylene）四萜类化合物的天然产物家庭的gukulenins。gukulenins是从红色海绵Phorbas Gukulensis的样品中分离出来的。已显示古枯菌素在体内和体外对各种癌细胞系是有效的细胞毒性剂（古枯菌素A）。迄今分离的8种gukulenins中有7种具有独特的六环双（α-tropolylene）分子结构，具有10个手性中心和1个手性轴。到目前为止，古枯菌素的结构解析是基于核磁共振实验的解释，并将通过我们的全合成古枯菌素A来验证。我们全合成gukulenin A的动机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，全合成gukulenin A需要创新的合成方法。随着德马约反应的进一步发展，我们在第一个供资期间已经在这方面作出了明显的贡献。在第二个供资期内，还必须进一步开发合成方法，特别是关于α-环酚酮的化学。如果我们的项目成功，我们将能够支持进一步研究gukulenins的生物活性，尽管从海绵中获得的有限。

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.