Asymmetric Synthesis of Highly Functional Pyrrolidines

本项目致力于开发不对称亚甲基叶立德环加成反应的新合成方法。通过提高反应的效率和通用性，特别强调不对称合成，所产生的方法将能够有效地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。将要研究的1，3-偶极环加成反应将涉及无环和环甲亚胺叶立德。将详细考察底物手性、手性助剂和手性催化剂对立体化学产物的影响。抗肿瘤抗生素氰环素A和比奥沙霉素的高效靶向合成将被开发出来，并将长期适用于结构相关的Dnacine的合成。凭借这一奖项，有机和高分子化学计划支持凯斯西储大学化学系的菲利普·P·加纳博士的研究。加纳教授和他的学生正在开发高效、可控地合成环状含氮化合物的新方法。所得到的方法随后被用于构建相关的天然化合物，从而说明了新的合成方法的力量，提供了比从自然来源获得的更多的化合物的途径，并促进了可能导致未来发现下一代药物的非天然类似物的合成。该项目将来自不同文化背景的研究生和本科生聚集在一起，朝着共同的目标努力，并为研究生提供了一个担任本科生导师的机会。

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.