SYNTHESIS OF OPTICALLY PURE OXYGENATED CYCLOPENTANOIDS

光学纯含氧环戊烷的合成

• 批准号: 3175655
• 负责人: CARL RANDOLPH JOHNSON
• 金额: $ 11.36万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-05-01 至 1988-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3175655
• 关键词: DNA directed DNA polymerase; antineoplastics; antiviral agents; cyclopentane; drug design /synthesis /production; optics; prostaglandins

The specific aims of the research proposed are: (1) The development of an efficient method for the enantioconvergent production of an optically pure intermediate (a protected 4,5-dihydroxy-2-cyclopenten-1-one) of broad utility in the synthesis of a variety of biologically active oxygenated cyclopenanoids. (2) Optimization of the utilizaton of this intermediate in the development of a synthesis of the antitumor carbocyclic nucleoside, (-)-neplanocin A, by exploration of a number of synthetic pathways. (3) Utilization of the intermediate developed in (1) and the chemistry explored in (2) to synthesize a number of neplanocin A analogues (in which the base component has been altered) for screening as antitumor and/or antiviral agents. (4) Conversion of the intermediate noted in (1) into an optically pure form of "(-)-carbocyclic ribose" and conversion of this to the antibiotic (-)-aristeromycin. (5) Demonstration of the utility of the intermediate noted in (1) in the synthesis of an optically pure prostaglandin and other biologically interesting natural products. (6) Synthesis of simplified prostanoid targets which contain enone or latent enont functionality for screening in an effort to establish structure/activity relationships, particularly as DNA polymerase inhibitors, for compounds of this class as antineoplastic agents.

提出的研究的具体目的是： （1）开发对映体的有效方法 产生光学纯中间体（受保护 4,5-二羟基-2-Cyclopenten-1-1-1-）在合成中的广泛效用 各种生物活性的含氧环烯素。 （2）在开发中优化该中间体的利用 抗肿瘤碳环核苷的合成，（ - ） - 内皮蛋白A， 通过探索许多合成途径。 （3）在（1）和化学中开发的中间体的利用 在（2）中探索以合成许多Neplanocin A类似物（其中 基础成分已更改）作为抗肿瘤和/或 抗病毒药。 （4）将（1）中指出的中间体转化为光学纯形形式 of“（ - ） - 碳环核糖”，并将其转换为抗生素 （ - ） - 瘤霉素。 （5）在（1）中指出的中间体的实用性的演示 光学纯前列腺素和其他生物学的合成 有趣的天然产品。 （6）合成包含eNONE或 筛查的潜在Enont功能以建立 结构/活性关系，特别是作为DNA聚合酶 抑制剂，作为抗肿瘤剂的该类别的化合物。