Expanding Radical SAM Chemistry by Using Radical Addition Reactions and SAM Analogues
Expanding Radical SAM Chemistry by Using Radical Addition Reactions and SAM Analogues
复制标题
使用自由基加成反应和 SAM 类似物扩展自由基 SAM 化学
DOI：
10.1002/anie.201605917
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发表时间：
2016-09-19
影响因子：
16.6
通讯作者：
Zhang, Qi
中科院分区：
文献类型：
--
作者：
Ji, Xinjian;Li, Yongzhen;Zhang, Qi
自由基S-腺苷-L-甲硫氨酸（SAM）酶利用[4Fe-4S]簇结合SAM并还原性切割其碳-硫键以产生高度反应性的5 '-脱氧腺苷（dAdo）自由基。几乎在所有情况下，dAdo自由基都会从底物或酶中提取一个氢原子，从而引发一系列高度多样化的反应。在这里，我们报告的dAdo自由基为基础的化学从氢提取自由基加成自由基SAM酶NosL的反应中的变化。这种变化是通过使用含有烯烃部分的底物类似物实现的。我们还表明，两个SAM类似物含有不同的核苷功能启动自由基为基础的反应，具有高效率。在反应中产生的烯烃的自由基加合物被发现经历两个不同的反应，并详细研究了这一过程的机理见解。我们的研究证明了一种有前途的策略，在扩大自由基SAM化学，提供了一种有效的方法来获得核苷的化合物，通过使用自由基SAM依赖的反应。
Radical S-adenosyl-l-methionine (SAM) enzymes utilize a [4Fe-4S] cluster to bind SAM and reductively cleave its carbon-sulfur bond to produce a highly reactive 5'-deoxyadenosyl (dAdo) radical. In almost all cases, the dAdo radical abstracts a hydrogen atom from the substrates or from enzymes, thereby initiating a highly diverse array of reactions. Herein, we report a change of the dAdo radical-based chemistry from hydrogen abstraction to radical addition in the reaction of the radical SAM enzyme NosL. This change was achieved by using a substrate analogue containing an olefin moiety. We also showed that two SAM analogues containing different nucleoside functionalities initiate the radical-based reactions with high efficiencies. The radical adduct with the olefin produced in the reaction was found to undergo two divergent reactions, and the mechanistic insights into this process were investigated in detail. Our study demonstrates a promising strategy in expanding radical SAM chemistry, providing an effective way to access nucleosidecontaining compounds by using radical SAM-dependent reactions.