Development of Pummerer-Based Oxidative Cyclization Chemistry for Natural Products Synthesis

螺环是在吲哚或咪唑核上形成的一系列天然生物碱，具有广泛的生物学活性，包括抗癌和抗菌活性。因此，全合成研究可能会通过提供宏观数量的天然产品以及作为药物制剂的铅开发的结构类似物来影响这些更大的健康问题。在这个持续进行的项目中，将探索将一种新的方法应用于这些具有立体化学挑战性的目标类型。这一化学源于在前一次赠款期间发展起来的泵工人氧化化学的最新进展。该奖项通过国家科学基金会的有机和高分子化学项目支持宾夕法尼亚州立大学化学系的肯·费尔德曼教授的研究。费尔德曼教授致力于开发新的策略和新的化学反应，以有效地构建具有生物活性的复杂天然产品。对这些研究目标的成功起诉可能导致新的药物线索，这反过来将对美国的制药企业产生有利影响。

Spirocycles formed from formal oxidative cyclization onto indole or imidazole cores comprise a diverse family of naturally occurring alkaloids that exhibit a wide range of promising biological properties, including anticancer and antibiotic activity. Consequently, total synthesis studies may impact on these larger health concerns by providing the natural products in macroscopic quantities along with structural analogues for lead development as pharmaceutical agents. In this continuing project, the application of a new approach to these stereochemically challenging types of targets will be explored. This chemistry stems from recent advances in Pummerer oxidation chemistry developed during the former grant period. Targets include dibromoagelaspongin, palau'amine, and the axinellamines.This award through the Organic and Macromolecular Chemistry Program of the National Science Foundation supports the research of Professor Ken Feldman in the Department of Chemistry at the Pennsylvania State University. Professor Feldman's research efforts focus on the development of new strategies and new chemical reactions for the efficient construction of complex, biologically active natural products. Successful prosecution of these research objectives may lead to new drug leads, which in turn will impact favorably on the pharmaceutical enterprise in the United States.