New Stereoselective Radical Cyclizations

本项目的重点是在三个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。适用于具有众多立体中心和官能团的底物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兼容的一种方法是将反应发展研究纳入天然产物的总合成。因此，在合成生物碱Acuumine、Lyconadin A和Hirsuellone A/D的过程中，将研究三个新的自由基环化反应，每个反应产生两个立体中心。在Acuumine的合成过程中，将探索由分子内芳基自由基共轭加成、烯醇形成和羟基化组成的自由基-极性交叉反应。Lyconadin A合成的核心是一个串联的过程，其特点是7-外酰基环化。这些毛状体酮的合成将被用作开发12-内酰基大环化的领域。自由基环化反应之所以被选中进行研究，是因为它温和的反应条件和级联转化的潜力使它们对合成化学家具有吸引力。有了这个奖项，有机和高分子化学计划支持杨百翰大学化学和生物化学系的Steven L.Castle教授的研究。卡塞尔教授的研究工作围绕着新的激进环化反应的发展展开。该化学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，如制药、农用化学品和材料(聚合物)行业的研究人员。

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.