LITHIUM PERCHLORATE DIETHYL ETHER MEDIATED REACTIONS

高氯酸锂二乙醚介导的反应

• 批准号: 2177071
• 负责人: PAUL A GRIECO
• 金额: $ 23.98万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-07-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2177071
• 关键词: Diels Alder reaction; chemical addition; chemical synthesis; ibogaine; lithium; molecular polarity; paclitaxel; sex hormone analog; stereochemistry; steroid analog

The major focus of this grant renewal application is to probe further the reactivity and selectivity of a number of organic reactions in highly polar media such as 3.0-5.0 M lithium perchlorate-diethyl ether with applications to molecules of biological interest. This proposal is divided into three parts. The first part of this proposal concentrates on ionic Diels-Alder reactions with applications to the total synthesis of endiandric acid A, 11-oxosteroids, and lycopodine. All studies proposed in this area will be of a fundamental nature in order to define limits and scope of this potentially useful reaction. The second part focuses on cationic [5+2] cycloaddition reactions which have received only scant attention during the past 30 years despite the potential it holds for those engaged in the synthesis of natural and unnatural products. We have found that the yields can be dramatically improved by employing 3.0 M LiClO4-EtOAc in the presence of trimethylsilyl triflate. We propose to examine a number of inter- and intramolecular cationic [5+2] cycloaddition reactions in order to determine the generality of our findings. We propose to apply the above chemistry to the total synthesis of the novel non- steroidal estrogen, miroestrol. In addition we plan to prepare a number of bicyclo [5.3.1] systems related to taxol. In the final section, we will focus on completion of a synthesis of tabersonine and development of a novel approach to iboga alkaloids.

本次赠款续展申请的主要重点是进一步探讨 许多有机反应的反应活性和选择性 极性介质，例如 3.0-5.0 M 高氯酸锂-乙醚 应用于具有生物学意义的分子。 这个提议是 分为三个部分。 该提案的第一部分集中于 离子 Diels-Alder 反应及其在全合成中的应用 Endiandric Acid A、11-oxosteroids 和 Lycopodine。提出的所有研究 该领域将具有基本性质，以便界定限制和 这种潜在有用反应的范围。 第二部分重点讨论 阳离子[5+2]环加成反应仅收到很少的 尽管其潜力巨大，但在过去 30 年中仍受到关注 从事天然和非天然产品合成的人员。我们有 发现采用 3.0 M 可以显着提高产量 在三氟甲磺酸三甲基甲硅烷基酯存在下，LiClO4-EtOAc。 我们建议 检查许多分子间和分子内阳离子 [5+2] 环加成 反应以确定我们的研究结果的普遍性。我们建议 将上述化学应用于新型非-的全合成 类固醇雌激素，miroestrol。 另外我们计划准备一些 与紫杉醇相关的双环[5.3.1]系统。 在最后一节中，我们 将重点完成 tabersonine 的合成和开发 一种获取伊博加生物碱的新方法。