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

由吲哚或咪唑核上的形式氧化环化形成的螺环包括天然存在的生物碱的不同家族，其表现出广泛的有前途的生物学性质，包括抗癌和抗生素活性。 因此，全合成研究可能会影响这些更大的健康问题，通过提供宏观量的天然产物沿着结构类似物的铅开发作为药物制剂。 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。 这种化学反应源于前一个赠款期间开发的Pummerer氧化化学的最新进展。 目标包括dibromoagelaspongin，帕劳'amine，和axinellamines.这个奖项通过美国国家科学基金会的有机和大分子化学计划支持肯·费尔德曼教授在宾夕法尼亚州立大学化学系的研究。 Feldman教授的研究重点是开发新的策略和新的化学反应，以有效构建复杂的、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导致新的药物线索，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.