C-C Bond Formation via Alkyl Cobaloxime Radical Chemistry: New Synthetic Reactions and Bio-Organic Applications

通过烷基钴肟自由基化学形成 C-C 键：新的合成反应和生物有机应用

• 批准号: 8806805
• 负责人: Bruce Branchaud
• 金额: $ 19.79万
• 依托单位: University of Oregon Eugene
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1992-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8806805&HistoricalAwards=false
• 关键词: Bond; Formation; via; Alkyl; Cobaloxime

The Organic and Macromolecular Program is supporting research directed toward the study of organometallic reagents related to vitamin B12. A series of novel chemical reactions have been discovered in which organo-cobalt (III) reagents mediate the cross coupling of varied structure types which leads to the construction of several biologically important compounds. Three different types of novel radical cross coupling reactions mediated via alkyl cobaloximes ıR-CoIII(dmgH)2py; dmgH = dimethylglyoxime monoanion! are being studied: (1) alkyl-alkenyl cross coupling, (2) alkyl-protonated heteroaromatic cross coupling, and (3) alkyl-nitroalkylanion cross coupling. A unique feature of these radical-mediated reactions, compared to other synthetically important radical reactions, is regeneration of the original olefin, protonated heteroaromatic, or nitroalkylanion functionality in the product. This research will continue the study of cobaloxime-mediated cross couplings and applications to (1) the development of a radical equivalent to the Grignard reaction, compatible with hydroxylic solvents and most of the common organic functional groups, via stoichiometric alkyl-nitroakylanion cross coupling, (2) a synthesis of the nucleoside antibiotic tunicamycin V and the development of a general strategy for the preparation of tunicamycins and analogs via stoichiometric alkyl-nitroalkylanion cross couplings, (3) a general strategy for the synthesis of C-di-, C-oligo-, and C-polysaccharides, essentially unexplored classes of bio-organically interesting and potentially significant unnatural analogs of natural products, via alkyl-nitroalkylanion cross coupling of valuable monosaccharides, and (4) preparation of two new classes of penicillin analogs, designed to be mechanism-based inhibitors of bacterial beta-lactamase self-defense enzymes, via alkyl-alkenyl or alkyl-protonated heteroaromatic cross couplings.

有机和高分子计划支持研究 针对与以下有关的有机金属试剂的研究 维生素B12 一系列新颖的化学反应已经被 发现其中有机钴（III）试剂介导 不同结构类型的交叉耦合， 构建几种重要的生物化合物。 三种不同类型的新型自由基交叉偶联反应 通过烷基钴肟介导的<$R-CoIII（dmgH）2 py; dmgH = 丁二酮肟单阴离子！正在研究：（1） 烷基-烯基交叉偶联，（2）烷基质子化 杂芳族交叉偶联，和（3）烷基-硝基烷基阴离子 交叉耦合 这些由自由基介导的 与其他重要的合成自由基相比， 反应，是原始烯烃的再生，质子化 杂芳族或硝基烷基阴离子官能团 产品 本研究将继续对钴胺素介导的 交叉耦合和应用（1）开发一个 自由基等价于Grignard反应，与 羟基溶剂和大多数常见的有机官能团 基团，通过化学计量的烷基-硝基烷基阴离子交叉偶联， (2)核苷抗生素衣霉素V的合成， 制定一项总体战略， 衣霉素和类似物通过化学计量 烷基-硝基烷基阴离子交叉偶联，（3）一般策略 为了合成C-二糖、C-寡糖和C-多糖， 基本上未被探索的生物有机有趣的类 和潜在的重要的非天然类似物， 产品，通过烷基-硝基烷基阴离子交叉偶联有价值的 单糖，和（4）制备两个新的类别， 青霉素类似物，被设计为基于机制的抑制剂 细菌β-内酰胺酶的自我防御酶，通过 烷基-烯基或烷基-质子化杂芳族交叉 联轴节.