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）：该提案提出了开发涉及手性联烯基羰基化合物的新有机反应的研究计划，旨在促进吡喃双环天然产物的合成。许多含有吡喃环的化合物表现出抗肿瘤、HIV 感染和炎症的重要生物活性。为了探索吡喃天然产物家族各个重要成员的药用潜力，提出了一种创新的通用化学合成策略。具体来说，讨论了三种含吡喃化合物的合成 - 哈巴苷（一种抗炎化合物）和两种简化的赭石酮类似物（一种抗 HIV 药物）。预计的合成赭石酮类似物和哈巴苷的路线涉及三个新反应的开发，第一个是强大的分子内狄尔斯-阿尔德环化。该提案中包含的初步数据首次证明了联烯基羰基（作为二烯等价物）与乙烯基硒亲双烯体进行狄尔斯-阿尔德反应的可行性。该提案的第二个目标涉及通过控制双键几何形状形成乙烯基硒化合物。第三，描述了一种新的锰络合/重排反应以产生非外消旋联烯基羰基化合物。除了在这项拟议工作中的应用之外，这三个关键反应一起也有望促进未来各种吡喃双环化合物的合成。