ORGANOMANGANESE REAGENTS IN ORGANIC SYNTHESIS

有机合成中的有机锰试剂

• 批准号: 3297026
• 负责人: PHILIP Ridley DESHONG
• 金额: $ 12.34万
• 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/3297026
• 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.

该研究建议描述了一系列旨在探测的实验 有条件的五角骨苯丙基复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。 这些包括确定范围和限制 顺序插入反应，用于制备的新方法 高度官能化的锰配合物，特别是糖基曼种植 复合物和顺序插入的分子内变体 反应。 提案的第二部分描述了 有机友试剂与C-糖基物质的总合成 tiazofurin（NSC-286193），硒苏富林和吡afur蛋白在光学上活跃 形式。 tiazofurin和selenazofurin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 对刘易斯肺癌和L1210和p388的物质具有活性 体内白血病。 吡afur蛋白是一种从链霉菌分离的C-核苷， 抗肿瘤和广谱抗病毒活性。 吡唑富林抑制 复制离子，单纯疱疹，麻疹，犀牛和流感的复制 病毒以及小鼠的朋友和Rauscher白血病病毒。 文化的诺维科夫 大鼠肝脏细胞，HeLa细胞和小鼠L细胞也对 吡af菜。 该提案的最后一部分描述了 有机团长的五核酸元复合物的利用来合成 在天然产物中发现的系统，例如C-糖化糖基化合物和 聚醚系统。 在此研究中合成的化合物 将用作乙霉菌素B总合成的模型化合物， pluramycin，Chrysomycin B，Lasolocid和Monensin。