Singh Ritesh, Bordeaux Melanie, Fasan Rudi
Department of Chemistry, University of Rochester, Rochester, New York 14627.
ACS Catal. 2014 Jan 6;4(2):546-552. doi: 10.1021/cs400893n.
The direct amination of aliphatic C-H bonds represents a most valuable transformation in organic chemistry. While a number of transition metal-based catalysts have been developed and investigated for this purpose, the possibility to execute this transformation with biological catalysts has remained largely unexplored. Here, we report that cytochrome P450 enzymes can serve as efficient catalysts for mediating intramolecular benzylic C-H amination reactions in a variety of arylsulfonyl azide compouds. Under optimized conditions, the P450 catalysts were found to support up to 390 total turnovers leading to the formation of the desired sultam products with excellent regioselectivity. In addition, the chiral environment provided by the enzyme active site allowed for the reaction to proceed in a stereo- and enantioselective manner. The C-H amination activity, substrate profile, and enantio/stereoselectivity of these catalysts could be modulated by utilizing enzyme variants with engineered active sites.
脂肪族碳氢键的直接胺化反应是有机化学中一项极具价值的转化反应。尽管已经开发并研究了多种基于过渡金属的催化剂用于此目的，但利用生物催化剂实现这种转化的可能性在很大程度上仍未得到探索。在此，我们报道细胞色素P450酶可以作为高效催化剂，介导多种芳基磺酰叠氮化合物的分子内苄基碳氢键胺化反应。在优化条件下，发现P450催化剂能够支持高达390次的总周转数，以优异的区域选择性生成所需的磺内酰胺产物。此外，酶活性位点提供的手性环境使反应能够以立体和对映选择性的方式进行。通过利用具有工程化活性位点的酶变体，可以调节这些催化剂的碳氢键胺化活性、底物谱以及对映/立体选择性。
