Intramolecular C(sp(3))H amination of arylsulfonyl azides with engineered and artificial myoglobin-based catalysts.
Intramolecular C(sp(3))H amination of arylsulfonyl azides with engineered and artificial myoglobin-based catalysts.
复制标题
DOI：
10.1016/j.bmc.2014.05.015
复制
发表时间：
2014-10-15
影响因子：
3.5
通讯作者：
Fasan R
中科院分区：
文献类型：
--
作者：
Bordeaux M;Singh R;Fasan R
脂肪族CH键直接转化为CN键为在有机分子中引入含氮官能团提供了一种有吸引力的方法。继我们最近发现细胞色素 P450 酶可以通过分子内 C(sp3)-H 胺化反应催化芳基磺酰叠氮化合物的环化后，我们在此探索了其他血红素蛋白的 C-H 胺化反应性。各种含血红素的蛋白质，特别是肌红蛋白和辣根过氧化物酶，被发现能够催化这种转化。基于这一发现，制备了一系列分别含有活性位点突变和非天然Mn-和Co-原卟啉IX辅因子的工程和人工肌红蛋白变体，以研究这些结构变化对这些催化剂的催化活性和选择性的影响。我们的研究表明，金属取代的肌红蛋白构成了可行的 C-H 胺化催化剂，与合成金属卟啉对应物相比，显示出独特的反应性趋势。另一方面，发现血红素口袋水平的氨基酸取代有利于提高这些 Mb 催化反应的立体选择性和对映选择性。涉及动力学同位素效应实验的机理研究表明，CH 键断裂与肌红蛋白催化芳基磺酰叠氮化物胺化的限速步骤有关。总之，这些研究表明肌红蛋白构成了设计和开发 C-H 胺化催化剂的有前途的支架。
The direct conversion of aliphatic C—H bonds into C—N bonds provides an attractive approach to the introduction of nitrogen-containing functionalities in organic molecules. Following our recent discovery that cytochrome P450 enzymes can catalyze the cyclization of arylsulfonyl azide compounds via an intramolecular C(sp3)—H amination reaction, we have explored here the C—H amination reactivity of other hemoproteins. Various heme-containing proteins, and in particular myoglobin and horseradish peroxidase, were found to be capable of catalyzing this transformation. Based on this finding, a series of engineered and artificial myoglobin variants containing active site mutations and non-native Mn- and Co-protoporphyrin IX cofactors, respectively, were preparedWmvestigate the effect of these structural changes on the catalytic activity and selectivity of to these catalysts. Our studies showed that metallo-substituted myoglobins constitute viable C—H amination catalysts, revealing a distinctive reactivity trend as compared to synthetic metalloporphyrin counterparts. On the other hand, amino acid substitutions at the level of the heme pocket were found to be beneficial toward improving the stereo- and enantioselectivity of these Mb-catalyzed reactions. Mechanistic studies involving kinetic isotope effect experiments indicate that C—H bond cleavage is implicated in the rate-limiting step of myoglobin-catalyzed amination of arylsulfonyl azides. Altogether, these studies indicate that myoglobin constitutes a promising scaffold for the design and development of C— H amination catalysts.
登录
查看更多内容
影响因子：
15
作者：
Lelyveld VS;Brustad E;Arnold FH;Jasanoff A
通讯作者：
Jasanoff A
DOI：
10.1126/science.1207203
发表时间：
2011-08-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Park HS;Hohn MJ;Umehara T;Guo LT;Osborne EM;Benner J;Noren CJ;Rinehart J;Söll D
通讯作者：
Söll D
DOI：
10.1039/c39820001400
发表时间：
1982-01-01
影响因子：
--
作者：
BRESLOW, R;GELLMAN, SH
通讯作者：
GELLMAN, SH
影响因子：
16.6
作者：
Cui, Y;He, C
通讯作者：
He, C
影响因子：
16.6
作者：
McIntosh, John A.;Coelho, Pedro S.;Farwell, Christopher C.;Wang, Z. Jane;Lewis, Jared C.;Brown, Tristan R.;Arnold, Frances H.
通讯作者：
Arnold, Frances H.