Investigation of Marine and Terrestrial Natural Products

该项目侧重于开发合成复杂天然产物的新方法。氮杂环环丙胺的合成和断裂将被检查，以评估这些不寻常的化合物作为新的手性构建块。本文将利用一种新的反应在环肽生物碱中构造烷基芳基醚，用于合成一种含有手性叔烷基芳基醚片段的环肽生物碱鲸烷酸D。铜和钯催化的方法将提供这种在食品化学中具有重要意义的天然产物的足够数量，以澄清不一致的毒性数据并建立罗克福汀C与草氨酸的关系。将开发新的影响大环化的偶联策略，并将其应用于合成一种具有不稳定官能团的应变[9]副环烷pondaplin。还将探索一种新的具有合成挑战性的天然产物，trichodermamide a的合成，从而对青霉嗪的推定结构进行评估。有了这个奖项，有机和大分子化学项目支持宾夕法尼亚大学化学系的Madeleine M. Joullie博士的研究。虽然天然来源提供了许多具有生物活性的令人着迷的化合物，但它们通常数量不足，来源不可靠，并且/或由于不良副作用而不适合用作药物。因此，“从零开始”合成复杂的有机化学品是一项必要的努力。朱丽教授和她的学生正在开发新的方法，解决不寻常的结构特征，以合成复杂的天然产物。他们的目标包括一种新的化合物，洛克福汀C，它在食品化学中非常重要，因为它存在于蓝纹奶酪中，而且目前可用的毒性数据不一致。

This project focuses on the development of new methods for the synthesis of complex natural products. The synthesis and fragmentation of azabicyclic cyclopropylamines will be examined to evaluate these unusual compounds as novel chiral building blocks. A new reaction permitting the construction of the alkyl-aryl ether in cyclopeptide alkaloids will be utilized in the synthesis of ceanothine D, a cyclopeptide alkaloid that contains a chiral tertiary alkyl-aryl ether moiety. A copper and palladium-catalyzed approach for the synthesis of roquefortine C will provide this natural product, of great importance in food chemistry, in sufficient quantity to permit clarification of inconsistent toxicity data and establishment of the relationship of roquefortine C to oxaline. New coupling strategies effecting macrocyclization will be developed and applied to the synthesis of pondaplin, a strained [9]paracyclophane with labile functionalities. The synthesis of a new synthetically challenging natural product, trichodermamide A, will also be explored, permitting an assessment of the putative structure of penicillazine.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Madeleine M. Joullie of the Department of Chemistry at the University of Pennsylvania. While natural sources provide many fascinating chemical compounds with promising biological activity, often they are available in insufficient quantities, derived from unreliable sources, and/or inappropriate as drugs due to undesirable side effects. Thus, the synthesis of complex organic chemicals "from scratch" is an essential endeavor. Professor Joullie and her students are developing novel methods, addressing unusual structural features, for the synthesis of complex natural products. Their targets include a novel compound, roquefortine C, that is of great importance in food chemistry, given its presence in blue cheese and inconsistencies in currently available toxicity data.