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.

有机和高分子计划正在支持与维生素 B12 相关的有机金属试剂的研究。 人们发现了一系列新颖的化学反应，其中有机钴（III）试剂介导不同结构类型的交叉偶联，从而构建了几种具有重要生物学意义的化合物。 通过烷基钴肟 ıR-CoIII(dmgH)2py 介导的三种不同类型的新型自由基交叉偶联反应； dmgH = 二甲基乙二肟单阴离子！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偶联。 与其他合成上重要的自由基反应相比，这些自由基介导的反应的一个独特特征是产物中原始烯烃、质子化杂芳族或硝基烷基阴离子官能团的再生。 本研究将继续研究钴肟介导的交叉偶联及其应用：(1) 通过化学计量的烷基-硝基烷基阴离子交叉偶联，开发相当于格氏反应的自由基，与羟基溶剂和大多数常见有机官能团相容，(2) 核苷类抗生素衣霉素 V 的合成以及 通过化学计量的烷基-硝基烷基阴离子交叉偶联制备衣霉素及其类似物的一般策略，（3）通过烷基-硝基烷基阴离子交叉偶联合成C-二糖、C-寡糖和C-多糖的一般策略，这些糖本质上是未开发的生物有机有趣且潜在重要的天然产物非天然类似物类别 有价值的单糖，以及（4）通过烷基-烯基或烷基质子化杂芳族交叉偶联制备两类新的青霉素类似物，旨在成为细菌β-内酰胺酶自卫酶的基于机制的抑制剂。