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.

该研究计划描述了一系列旨在探索的实验 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。 提案 由三个部分组成。 首先，方法论研究是 概述。 其中包括确定范围和限制 顺序插入反应，制备的新方法 高功能化的锰络合物，特别是糖基锰 复合物和顺序插入的分子内变体 反应。 该提案的第二部分描述了应用 C-糖基物质全合成有机锰试剂 光学活性的噻唑呋林 (NSC-286193)、硒唑呋林和吡唑呋林 形式。 噻唑呋林和硒唑呋林是合成的 C-核苷， 具有有效的抗病毒和抗肿瘤活性。 例如，两者 物质对 Lewis 肺癌以及 L1210 和 P388 具有活性 体内白血病。 吡唑呋林 (Pyrazofurin) 是一种从链霉菌 (Streptomyces candidus) 中分离出来的 C-核苷，具有 抗肿瘤和广谱抗病毒活性。 吡唑呋林抑制 牛痘、单纯疱疹、麻疹、犀牛和流感的复制 病毒，以及小鼠体内的弗兰德和劳舍白血病病毒。 培养诺维科夫 大鼠肝细胞、HeLa 细胞和小鼠 L 细胞也对 吡唑呋林。 该提案的最后一部分描述了初步研究 五羰基有机锰配合物在合成中的应用 天然产物中发现的系统，例如 C-芳基化糖基化合物和 聚醚系统。 本研究期间合成的化合物 将作为 vineomycin B 全合成的模型化合物， 多霉素、红霉素B、拉索洛西和莫能菌素。