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.

有机和大分子计划正在支持针对研究与维生素B12相关的有机试剂研究的研究。已经发现了一系列新型的化学反应，其中有机粘液（III）试剂介导了各种结构类型的交叉耦合，从而导致构建几种具有生物学上重要的化合物。三种不同类型的新型自由基交叉耦合反应是通过烷基钴氧III（DMGH）2PY介导的； dmgh =二甲基乙酰胺单声道！正在研究：（1）烷基 - 烯基交叉耦合，（2）烷基 - 促成的异芳族交叉耦合，以及（3）烷基甲丙基烷基烷基烷基交叉耦合。与其他重要的自由基反应相比，这些自由基介导的反应的独特特征是原始烯烃，质子化的杂芳族或硝基烷基烷基化功能的再生。这项研究将继续研究（1）与格里格纳德反应相等的根本性的钴毒介导的跨耦合和应用的研究，与羟基溶液和大多数常见的有机官能团通过stoichimememper arkyl-nitroakylyakylyakylyakylanion cronteration a Dreation a Dreation a Deventrion A and vartight and vetrient and（2）为了通过化学计量计量烷基苯甲酸氨基烷基跨耦合制备衣霉素和类似物，（3）一种一般策略，用于合成C-di-，c- oligo-和c-洛克糖和C-二糖，本质上是生物学上有趣且潜在的不一成外重要的自然产物的无效类似物的alkylyl-nIT，从本质上讲，基本上是意想不到的意外类似物，单糖和（4）通过烷基 - 烷基烯基或烷基促异的异芳族交叉耦合来制备两种新的青霉素类似物，设计为基于机制的细菌β-内酰胺酶自卫酶的基于机制的抑制剂。