ASYMMETRIC SYNTHESIS OF MEDIUM RING POLYETHERS

中环聚醚的不对称合成

• 批准号: 6351337
• 负责人: MICHAEL T. CRIMMINS
• 金额: $ 23.67万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2004-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6351337
• 关键词: antineoplastics; biological products; brevetoxin; cyclic compound; drug design /synthesis /production; ethers; stereochemistry

This new program will focus on the development of a novel strategy for the enantioselective synthesis of complex medium ring ether marine natural products. A practical asymmetric aldol addition followed by a ring closing metathesis reaction will be used to construct six to nine membered cyclic ethers. The ring closing metathesis reaction of medium rings can be effected without cyclic constraints by exploiting the gauche effect of adjacent oxygen substituents. This effect will be explored in a tandem ring opening-ring closing metathesis reaction for the simultaneous production of two medium-sized cyclic ethers. The methods for medium ring ether synthesis will be utilized in the synthesis of a variety of novel, pharmacologically active marine natural products such as isolaurallene, pannosallene, brevetoxin A, mucocin and gigantecin. Since many of the polyether toxins and the cytotoxic annonaceous acetogenins are available in very small quantities, chemical synthesis offers one solution to the supply problem for further studies on the mechanism of action and chemical modification of the toxins and antitumor agents, leading ultimately to improvements in public health.

该新计划将着重于制定复杂介质环醚天然产品的对映选择性合成的新型策略。 实用的不对称醛醇添加，然后进行环闭合反应反应构建六到九个成员的环状醚。 可以通过利用相邻的氧取代基的Gauche效应而无需循环限制而在无环状限制的情况下进行环的闭合分解反应。 该效应将在串联环开环闭合反应反应中探索，以同时生产两个中型环状醚。 中环醚合成的方法将用于多种新型的药理活性海洋天然产物（例如Inalaralallene，Pannosallene，Brevetosallene，Brevetoxin A，Mucocin和Gigantecin）的合成。由于许多聚醚毒素和细胞毒性的牛tacogenin的可用数量很少，因此化学合成为供应问题提供了一种解决方案，用于进一步研究毒素和抗肿瘤剂的作用机理和化学修饰，最终导致公共卫生改善。