New Stereoselective Radical Cyclizations

新的立体选择性自由基环化

• 批准号: 0716991
• 负责人: Steven Castle
• 金额: $ 35万
• 依托单位: Brigham Young University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2011-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0716991&HistoricalAwards=false
• 关键词: New; Stereoselective; Radical; Cyclizations

This project is focused on the discovery of new stereoselective radical cyclizations in the context of three alkaloid total syntheses. Synthetic methods that are applicable to substrates adorned with numerous stereocenters and functional groups are extremely valuable to researchers engaged in the synthesis of complex organic molecules. One way to ensure that new methodology is compatible with challenging substrates is to incorporate the reaction development studies into the total synthesis of a natural product. Accordingly, three novel radical cyclizations, each of which creates two stereocenters, will be investigated in the course of synthesizing the alkaloids acutumine, lyconadin A, and hirsutellones A/D. A radical?polar crossover reaction consisting of an intramolecular aryl radical conjugate addition followed by enolate formation and hydroxylation will be explored during the acutumine synthesis. The centerpiece of the lyconadin A synthesis is a tandem process featuring a 7-exo acyl radical cyclization. The synthesis of the hirsutellones will be used as an arena for developing a 12-endo acyl radical macrocyclization. Radical cyclizations have been selected for study because the mild reaction conditions and potential for cascade transformations render them attractive to synthetic chemists.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Steven L. Castle of the Department of Chemistry and Biochemistry at Brigham Young University. Professor Castle's research efforts revolve around the development of new radical cyclizations. This chemistry employs mild reaction conditions, which allow for compatibility with many sensitive functional groups that are present in organic molecules. Successful development of the methodology will positively impact researchers reliant upon chemical synthesis, such as those working in the pharmaceutical, agrochemical, and materials (polymer) industries.

本项目的重点是在三种生物碱全合成的背景下发现新的立体选择性自由基环化反应。 适用于装饰有许多立构中心和官能团的基底的合成方法对于从事复杂有机分子合成的研究人员来说是非常有价值的。 确保新方法与具有挑战性的底物相容的一种方法是将反应开发研究纳入天然产物的全合成中。 因此，三个新的自由基环化，其中每一个创建两个立体中心，将在合成生物碱acutumine，lyconadin A，和hirsutellones A/D的过程中进行研究。 激进分子？在acutumine合成过程中，将探索由分子内芳基共轭加成、随后烯醇化物形成和羟基化组成的极性交叉反应。 番茄红素A合成的核心是一个串联过程，其特征是7-外酰基自由基环化。 本论文的研究将为12-内酰基自由基大环化反应的开展提供一个竞技场。 自由基环化反应之所以被选中进行研究，是因为其温和的反应条件和级联转化的潜力使其对合成化学家具有吸引力。杨百翰大学化学与生物化学系的Castle。 卡斯尔教授的研究工作围绕着新的自由基环化的发展。 这种化学反应采用温和的反应条件，允许与有机分子中存在的许多敏感官能团相容。 该方法的成功开发将对依赖化学合成的研究人员产生积极影响，例如那些在制药，农业化学和材料（聚合物）行业工作的研究人员。