Asymmetric Synthesis of Highly Functional Pyrrolidines

本计画旨在发展不对称甲亚胺叶立德环加成反应之新合成方法。通过提高该反应的效率和通用性，特别强调不对称合成，所得到的方法将能够有效组装在许多生物活性天然产物和合成类似物中发现的各种复杂的吡咯烷结构。所研究的1，3-偶极环加成反应涉及无环和环状甲亚胺叶立德。居民基板手性，手性助剂和手性催化剂的立体化学结果的影响将被详细检查。将开发高效的靶向合成抗肿瘤抗生素氰环素A和双霉素，并长期应用于结构相关的dnacins的合成。有了这个奖项，有机和大分子化学计划将支持凯斯西储大学化学系的Philip P. Garner博士的研究。 Garner教授和他的学生正在开发新的方法，用于有效和可控地合成环状含氮化合物。然后将所得方法用于构建相关的天然存在的化合物，从而说明新合成方法的能力，提供比从天然来源获得的化合物更大量的化合物，并促进合成可能导致未来发现下一代药物的非天然类似物。该项目汇集了来自不同文化背景的研究生和本科生，共同努力实现共同的目标，并为研究生提供了一个机会，作为本科生的导师。

This project addresses the development of new synthetic methodology for asymmetric azomethine ylide cycloadditions. By increasing the efficiency and generality of this reaction, with a particular emphasis on asymmetric synthesis, the resulting methodology will enable the efficient assembly of a variety of complex pyrrolidine structures found in many bioactive natural products and synthetic analogs. The 1,3-dipolar cycloaddition reactions to be studied will involve both acyclic and cyclic azomethine ylides. The influence of resident substrate chirality, chiral auxiliaries, and chiral catalysts on the stereochemical outcome will be examined in detail. Efficient target-oriented syntheses of the antitumor antibiotics cyanocycline A and bioxalomycin will be developed, with longer-term applicability to the synthesis of the structurally related dnacins.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Philip P. Garner of the Department of Chemistry at Case Western Reserve University. Professor Garner and his students are developing new methods for the efficient and controlled synthesis of cyclic nitrogen-containing compounds. The resulting methods are then utilized in the construction of relevant naturally occurring compounds, thereby illustrating the power of the new synthetic methods, providing access to larger quantities of compounds than may be obtained from natural sources, and facilitating the synthesis of unnatural analogues that may lead to the future discovery of next generation pharmaceuticals. The project brings together graduate and undergraduate students from diverse cultural backgrounds to work together towards common goals and provides an opportunity for graduate students to serve as mentors to the undergraduates.