Total Synthesis of the Stephacidins

描述（由申请人提供）：拟定研究旨在设计和执行千金藤素的全合成，千金藤素是一种结构新颖的生物碱，对某些睾酮依赖性前列腺细胞系表现出强效体外细胞毒性活性。该提案包括几个新的战略，旨在访问经常性的6-羟吲哚基序在短期内从现成的材料。此外，提出了一种新的不寻常的双环[2.2.2]二氮杂辛烷核的不对称选择性的建设的方法。最后，希望能够找到可靠和有效地从母体吲哚制备吲哚基硝酮（亚胺N-氧化物）的条件。理想情况下，这些和其他策略将用于制备千金藤素本身以及类似物，不仅用于评价生物活性，而且用于阐明其作用的未知机制。

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.