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

有机和大分子计划正在支持针对与维生素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，在这些化学反应中，有机钴(III)试剂介导了不同结构类型的交叉偶联，导致了几个具有重要生物意义的化合物的构建。三种不同类型的烷基钴肟ıR-CoIII(DmgH)2py；dmgH=丁二酮肟！正被研究：(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在产物中再生原始的烯烃、质子化的杂芳烃或硝基烷基阴离子官能团。这项研究将继续研究钴肟介导的交叉偶联及其在以下方面的应用：(1)通过化学计量的烷基-硝基阴离子交叉偶联，开发一种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的合成和通过化学计量的烷基-硝基阴离子交叉偶联制备衣霉素及其类似物的通用策略的发展；(3)合成C-二、C-寡糖和C-多糖的通用策略，通过有价值的单糖的烷基-硝基阴离子交叉偶联，以及(4)制备两类新的青霉素类似物，旨在成为细菌β-内酰胺酶自我防御酶的基于机理的抑制剂，通过烷基-烯基或烷基-质子化杂芳烃的交叉偶联。

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.