New Stereoselective Radical Cyclizations

这个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。具有大量立体中心和官能团修饰的底物的合成方法对从事复杂有机分子合成的研究人员是非常有价值的。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全合成中。因此，在合成水仙碱、水仙碱A和毛酮A/D生物碱的过程中，将研究三种新的自由基环化，每一种都产生两个立体中心。一个激进的吗?研究了由分子内芳基共轭加成、烯酸酯形成和羟基化组成的极性交叉反应。lyconadin A合成的核心是一个以7-外显酰基环化为特征的串联过程。毛甾酮的合成将作为开发12-内端酰基大环化的舞台。选择自由基环化作为研究对象，是因为其温和的反应条件和潜在的级联转化对合成化学家很有吸引力。杨百翰大学化学与生物化学系的Steven L. Castle教授获得了这个奖项，这是有机与大分子化学项目对他的研究的支持。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，允许与存在于有机分子中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、农用化学和材料（聚合物）工业工作的研究人员。

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.