102362-98-1Relevant articles and documents
Versatile new reagent for nitrosation under mild conditions
Galloway, Jordan D.,Sarabia, Cristian,Fettinger, James C.,Hratchian, Hrant P.,Baxter, Ryan D.
supporting information, p. 3253 - 3258 (2021/05/06)
Here we report a new chemical reagent for transnitrosation under mild experimental conditions. This new reagent is stable to air and moisture across a broad range of temperatures and is effective for transnitrosation in multiple solvents. Compared with traditional nitrosation methods, our reagent shows high functional group tolerance for substrates that are susceptible to oxidation or reversible transnitrosation. Several challenging nitroso compounds are accessed here for the first time, including 15N isotopologues. X-ray data confirm that two rotational isomers of the reagent are configurationally stable at room temperature, although only one isomer is effective for transnitrosation. Computational analysis describes the energetics of rotamer interconversion, including interesting geometry-dependent hybridization effects.
Mechanism-Guided Design and Discovery of Efficient Cytochrome P450-Derived C-H Amination Biocatalysts
Fasan, Rudi,Kolev, Joshua N.,Ren, Xinkun,Steck, Viktoria
, p. 10343 - 10357 (2020/07/04)
Cytochromes P450 have been recently identified as a promising class of biocatalysts for mediating C-H aminations via nitrene transfer, a valuable transformation for forging new C-N bonds. The catalytic efficiency of P450s in these non-native transformations is however significantly inferior to that exhibited by these enzymes in their native monooxygenase function. Using a mechanism-guided strategy, we report here the rational design of a series of P450BM3-based variants with dramatically enhanced C-H amination activity acquired through disruption of the native proton relay network and other highly conserved structural elements within this class of enzymes. This approach further guided the identification of XplA and BezE, two atypical natural P450s implicated in the degradation of a man-made explosive and in benzastatins biosynthesis, respectively, as very efficient C-H aminases. Both XplA and BezE could be engineered to further improve their C-H amination reactivity, which demonstrates their evolvability for abiological reactions. These engineered and natural P450 catalysts can promote the intramolecular C-H amination of arylsulfonyl azides with over 10 000-14 000 catalytic turnovers, ranking among the most efficient nitrene transfer biocatalysts reported to date. Mechanistic and structure-reactivity studies provide insights into the origin of the C-H amination reactivity enhancement and highlight the divergent structural requirements inherent to supporting C-H amination versus C-H monooxygenation reactivity within this class of enzymes. Overall, this work provides new promising scaffolds for the development of nitrene transferases and demonstrates the value of mechanism-driven rational design as a strategy for improving the catalytic efficiency of metalloenzymes in the context of abiological transformations.
Chemoselective, enzymatic C-H bond amination catalyzed by a cytochrome P450 containing an Ir(Me)-PIX cofactor
Dydio, Pawel,Key, Hanna M.,Hayashi, Hiroki,Clark, Douglas S.,Hartwig, John F.
supporting information, p. 1750 - 1753 (2017/02/15)
Cytochrome P450 enzymes have been engineered to catalyze abiological C-H bond amination reactions, but the yields of these reactions have been limited by low chemoselectivity for the amination of C-H bonds over competing reduction of the azide substrate t
