Synthesis of Pyran Bicyclic Natural Products

吡喃双环天然产物的合成

基本信息

批准号：
6595792
负责人：
SALVATORE D LEPORE
金额：
$ 13.97万
依托单位：
FLORIDA ATLANTIC UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-04-10 至 2006-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6595792
关键词：
Diels Alder reaction alkenes antiAIDS agent antiinflammatory agents bicyclic compound biological products carbonyl group chemical synthesis diene manganese molecular rearrangement pyrans selenium stereochemistry

项目摘要

DESCRIPTION (provided by applicant): This proposal sets forth a research program for the development of new organic reactions involving chiral allenylcarbonyl compounds that aims to facilitate the synthesis of pyran bicyclic natural products. Numerous compounds containing the pyran ring exhibit important biological activity against tumors, HIV infection, and inflammation. To explore the medicinal potential of various important members of the family of pyran natural products, an innovative and general strategy for their chemical synthesis is proposed. Specifically, the synthesis of three pyran-containing compounds is discussed - harpagide, an anti-inflammatory compound, and two simplified analogs of ochrephilone, an anti-HIV agent. The projected route for the synthesis ochrephilone analogs and harpagide involves the development of three new reactions, the first being a powerful intramolecular Diels-Alder cyclization. Preliminary data included in the proposal demonstrate, for the first time, the feasibility of Diels-Alder reactions of allenyl carbonyl groups (as diene equivalents) with vinylselenium dienophiles. The second reaction targeted in this proposal involves the formation of vinylselenium compounds with control over the double-bond geometry. Thirdly, a novel manganese complexation/rearrangement reaction to give non-racemic allenyl carbonyl compounds is described. Besides their application in this proposed work, these three key reactions taken together are also expected to facilitate the future synthesis of a wide variety pyran bicyclic compounds.

描述（由申请人提供）：该提案阐明了一项研究计划，以开发涉及手性甲烯基辅助化合物的新有机反应，旨在促进Pyran Bicyclic Natural Products的合成。许多含有pyran环的化合物表现出针对肿瘤，HIV感染和炎症的重要生物学活性。为了探索Pyran天然产品家族的各种重要成员的药用潜力，提出了一种创新的一般策略。具体而言，讨论了三种含pyran的化合物的合成 - 竖鼠，一种抗炎化合物和两种简化的抗HIV剂Ochrephilone的简化类似物。合成纤维酮类似物和竖岩的投影途径涉及三个新反应的发展，第一种反应是强大的分子内DIELS-ALDER-alder环化。该提案中包含的初步数据首次证明，甲烯基羰基（作为二烯当量）与乙烯基替代二烯的可行性。该提案中针对的第二个反应涉及与双键几何形状控制的乙烯基替代化合物的形成。第三，描述了一种新型的锰络合/重排反应，从而描述了非流行甲烯基羰基化合物。除了在这项拟议的工作中应用它们外，这三个关键反应还有望促进未来多种pyran pyran双环化合物的综合。