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.

有机和大分子项目正在支持与维生素B12相关的有机金属试剂的研究。在一系列新的化学反应中，有机钴（III）试剂介导不同结构类型的交叉偶联，从而导致几种重要的生物化合物的构建。烷基钴酰肟ıR-CoIII(dmgH)2py介导的三种不同类型新型自由基交叉偶联反应二甲基甲氧肟单阴离子！主要研究有：(1)烷基-烯基交叉偶联，(2)烷基-质子化杂芳烃交叉偶联，(3)烷基-硝基烷基阴离子交叉偶联。与其他重要的合成自由基反应相比，这些自由基介导的反应有一个独特的特点，就是产物中原有的烯烃、质子化的杂芳烃或硝基烷基离子官能团的再生。本研究将继续研究钴胺肟介导的交叉偶联，并将其应用于：(1)通过化学计量烷基-硝基脲基离子交叉偶联，开发一种与格氏反应等效的自由基，与羟基溶剂和大多数常见的有机官能团兼容；(2)核苷类抗生素tunicamycin V的合成和通过化学计量烷基-硝基烷基脲离子交叉偶联制备tunicamycin及其类似物的一般策略的发展；(3)合成c -二-、c -寡-和c -多糖的一般策略；通过有价值的单糖的烷基-硝基烷基脲离子交叉偶联，基本上未开发的生物有机有趣和潜在重要的天然产物的非天然类似物，以及(4)制备两种新的青霉素类似物，设计为细菌β -内酰胺酶自卫酶的基于机制的抑制剂。通过烷基-烯基或烷基-质子化异芳烃交叉偶联。