Total Synthesis of the Stephacidins

描述（由申请人提供）：拟议的研究旨在设计和执行stephacidins的全合成，这是一种结构新颖的生物碱，在体外对某些睾酮依赖性前列腺细胞系表现出有效的细胞毒性活性。该提案包括几种新的策略，旨在从现成的材料中快速获取重复出现的6-氧吲哚基序。此外，还提出了一种特殊的双环[2.2.2]重氮辛烷核对映选择性构造的新方法。最后，希望能找到可靠、高效地从母体吲哚制备吲哚基硝基（亚胺n -氧化物）的条件。理想情况下，这些和其他策略将被用来制备stephacidins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运作的未知机制。

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.