Total Synthesis of the Stephacidins

描述(申请人提供)：这项拟议的研究旨在设计和执行对Stephacidins的全合成，Stephacidins是一种结构新颖的生物碱，在体外对某些睾酮依赖的前列腺细胞株具有强大的细胞毒活性。该提案包括几项新战略，旨在从现成的材料中迅速获得重复出现的6-氧吲哚基序。此外，还提出了一种新的构筑双环[2.2.2]重氮辛烷对映体的新方法。最后，希望能够找到从母体吲哚制备吲哚基硝酮(亚胺N-氧化物)的可靠和有效的条件。理想情况下，这些策略和其他策略将被用于制备千金鱼素本身以及类似物，不仅用于评估生物活性，而且还用于阐明它们的未知作用机制。

DESCRIPTION (provided by applicant): The proposed research is aimed at devising and executing a total synthesis of the stephacidins, structurally novel alkaloids that exhibit potent in vitro cytotoxic activity against certain testosterone-dependent prostate cell lines. The proposal includes several new strategies aimed at accessing the recurring 6-oxyindole motif in short order from readily available materials. In addition, a new method for the enantioselective construction of the unusual bicyclo[2.2.2]diazaoctane core is presented. Finally, it is hoped that conditions can be found to reliably and efficiently prepare indolyl nitrones (imine N-oxides) from the parent indoles. Ideally, these and other strategies would be used prepare the stephacidins themselves as well as analogs not only for evaluations of bioactivity, but also to elucidate the unknown mechanism by which they operate.