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

由吲哚或咪唑核形成的正式氧化环形成的螺旋环包括多种天然存在的生物碱，具有广泛的有前途的生物学特性，包括抗癌和抗生素活性。因此，全合成研究可以通过提供宏观数量的天然产物以及用于先导剂开发的结构类似物来影响这些更大的健康问题。在这个持续的项目中，将探索一种新方法在这些具有立体化学挑战性的目标类型中的应用。这种化学源于在前资助期间发展的彭默尔氧化化学的最新进展。靶点包括二溴松脂蛋白、帕劳胺和阿西那胺。该奖项通过美国国家科学基金会的有机和大分子化学项目来支持宾夕法尼亚州立大学化学系肯·费尔德曼教授的研究。费尔德曼教授的研究重点是开发新的策略和新的化学反应，以有效地构建复杂的、具有生物活性的天然产物。这些研究目标的成功实施可能会带来新的药物线索，这反过来又会对美国的制药企业产生有利的影响。

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.