ORGANOMANGANESE REAGENTS IN ORGANIC SYNTHESIS

有机合成中的有机锰试剂

• 批准号: 3297024
• 负责人: PHILIP Ridley DESHONG
• 金额: $ 14.27万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3297024
• 关键词: antineoplastics; antiviral agents; carbonyl compound; chemical synthesis; drug design /synthesis /production; glycosylation; manganese; monensin; nucleosides; organometallic compounds; reagent /indicator

This research proposal describes a series of experiments designed to probe the ability of organomanganese pentacarbonyl complexes to serve as reagents for the synthesis of structurally complex organic substances. The proposal is comprised of three sections. In the first, methodological studies are outlined. These include determination of the scope and limitation of the sequential insertion reaction, novel methodology for the preparation of highly functionalized manganese complexes, in particular glycosylmanganese complexes, and intramolecular variants of the sequential insertion reaction. The second section of the proposal describes the application of organomanganese reagents to the total synthesis of C-glycosyl substances tiazofurin (NSC-286193), selenazofurin, and pyrazofurin in optically active form. Tiazofurin and selenazofurin are synthetic C-nucleosides which possess potent antiviral and antitumor activity. For instance, both substances exhibit activity against Lewis lung carcinoma and L1210 and P388 leukemias in vivo. Pyrazofurin is a C-nucleoside isolated from Streptomyces candidus which has antitumor and broad spectrum antiviral activity. Pyrazofurin suppresses the replication of vaccinia, herpes simplex, measles, rhino and influenza viruses, and Friend and Rauscher leukemia virus in mice. Cultured Novikoff rat hepatome cells, HeLa cells and mouse L cells are also sensitive to pyrazofurin. The final section of the proposal describes preliminary studies of the utilization of organomanganese pentacarbonyl complexes for the synthesis of systems found in natural products such as C-arylated glycosyl compounds and polyether systems. The compounds synthesized during this investigation will serve as model compounds for the total synthesis of vineomycin B, pluramycin, chrysomycin B, lasolocid and monensin.

这项研究计划描述了一系列旨在探索 有机锰五羰基配合物作为试剂的能力 用于合成结构复杂的有机物质。 该提案 由三部分组成。 首先，方法论研究是 概述。 其中包括确定《公约》的范围和限制， 序贯插入反应，新的制备方法， 高度官能化的锰络合物，特别是糖基锰 复合物，以及顺序插入的分子内变体 反应 提案的第二部分介绍了 有机锰试剂在碳糖基物质全合成中的应用 噻唑弗林（NSC-286193），硒唑弗林，并在光学活性 form. 硫唑弗林和硒唑弗林是合成的C-核苷， 具有很强的抗病毒和抗肿瘤活性。 比方说都 对刘易斯肺癌和L 1210和P 388显示活性物质 体内白血病 吡唑呋啶是从白色链霉菌中分离的C-核苷， 抗肿瘤和广谱抗病毒活性。 吡唑弗林抑制 牛痘、单纯疱疹、麻疹、犀牛和流感的复制 病毒，以及小鼠中的Friend和Rauscher白血病病毒。 文化Novikoff 大鼠肝细胞、HeLa细胞和小鼠L细胞也对 阿佐弗林。 提案的最后一节介绍了对 利用有机锰五羰基配合物合成 天然产物中发现的系统，如C-芳基化糖基化合物， 聚醚体系 本研究中合成的化合物 将作为全合成长春霉素B的模型化合物， 普朗霉素、金霉素B、拉索罗菌素和莫能菌素。