Total Synthesis of the Stephacidins

千金藤菌素的全合成

• 批准号: 6948763
• 负责人: Carlos Ariel Guerrero
• 金额: $ 2.99万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2008-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6948763
• 关键词: chemical synthesis; indoles; method development; predoctoral investigator

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.

描述（由申请人提供）：拟议的研究旨在设计和执行斯蒂芬蛋白（结构新颖的生物碱）的完全合成，这些生物碱表现出有效的体外细胞毒性活性，以针对某些依赖睾丸激素的前列腺细胞系。该提案包括几种旨在从易于使用的材料的短期顺序访问重复的6-氧吲哚图案的新策略。此外，提出了一种新方法，用于对对映体构造不寻常的bicyclo [2.2.2] Dizaoctane Core。最后，希望可以发现条件可靠，有效地从母体吲哚制备吲哚基硝基（亚胺N-氧化物）。理想情况下，这些策略和其他策略将被使用准备史蒂芬蛋白本身以及类似物，不仅用于评估生物活性，而且还阐明了它们运作的未知机制。