Synthesis of Heterocyclic Natural Products

本研究项目涉及几种具有生物学和/或结构意义的复杂自然分子的立体特异性全合成。特别地，重点将放在生产和改进具有潜在广泛适用性的方法上，这将对参与化学治疗剂合成的有机和药物化学家具有实际用途。已经开始了一些具有挑战性的、结构独特的多环海洋苔藓虫生物碱的全合成工作，这些研究将在所要求的资助期间继续进行。具体而言，将完成chartelline A和securine A/securamine A的全合成。此外，对不寻常的Securinega生物碱secu的短对映选择性全合成的研究即将完成。通过一种新颖的串联多步工艺构建天然产物的独特四环环体系。美国国家科学基金会的有机和大分子化学项目用这个奖项来支持宾夕法尼亚州立大学化学系的Steven M. Weinreb教授的研究。Weinreb教授的研究工作主要围绕开发合成杂环有机化合物的高效新方法，并将这种化学应用于合成重要结构复杂的天然产物。该方法的成功发展将对制药和农业工业的中间体合成产生特别的影响。

This research program deals with the stereospecific total synthesis of several complex naturally-occurring molecules having biological and/or structural significance. In particular, emphasis will be placed upon producing and refining methodology having potentially broad applicability which will be of practical use to both organic and medicinal chemists involved in synthesis of chemotherapeutic agents. Work has been initiated on total syntheses of some of the challenging, structurally unique polycyclic marine bryozoan alkaloids of the chartelline/chartellamide/securamine group and these studies will be continued during the requested grant period. Specifically, total syntheses of chartelline A and securine A/securamine A will be completed. In addition, studies are nearing completion on a short enantioselective total synthesis of the unusual Securinega alkaloid secu?amamine A via a novel tandem multistep process to construct the unique tetracyclic ring system of the natural product. With this award, the Organic and Macromolecular Chemistry Program of NSF is supporting the research of Professor Steven M. Weinreb of the Department of Chemistry at Penn State University. Professor Weinreb's research efforts revolve primarily around the development of efficient new methodology for the synthesis of heterocyclic organic compounds, and applications of this chemistry to the synthesis of important structurally complex natural products. Successful development of the methodology will have particular impact on synthesis of intermediates in the pharmaceutical and agricultural industries.