36982-86-2Relevant academic research and scientific papers
Engineering Chemoselectivity in Hemoprotein-Catalyzed Indole Amidation
Brandenberg, Oliver F.,Miller, David C.,Markel, Ulrich,Ouald Chaib, Anissa,Arnold, Frances H.
, p. 8271 - 8275 (2019/08/22)
Here we report a cytochrome P450 variant that catalyzes C2-amidation of 1-methylindoles with tosyl azide via nitrene transfer. Before evolutionary optimization, the enzyme exhibited two undesired side reactivities resulting in reduction of the putative iron-nitrenoid intermediate or cycloaddition between the two substrates to form triazole products. We speculated that triazole formation was a promiscuous cycloaddition activity of the P450 heme domain, while sulfonamide formation likely arose from surplus electron transfer from the reductase domain. Directed evolution involving mutagenesis of both the heme and reductase domains delivered an enzyme providing the desired indole amidation products with up to 8400 turnovers, 90% yield, and a shift in chemoselectivity from 2:19:1 to 110:12:1 in favor of nitrene transfer over reduction or triazole formation. This work expands the substrate scope of hemoprotein nitrene transferases to heterocycles and highlights the adaptability of the P450 scaffold to solve challenging chemoselectivity problems in non-natural enzymatic catalysis.
Rhodium-catalyzed regioselective amidation of indoles with sulfonyl azides via C-H bond activation
Shi, Jingjing,Zhou, Bing,Yang, Yaxi,Li, Yuanchao
, p. 8953 - 8955 (2013/01/15)
Direct C-2 amidation of indoles was reported using sulfonyl azides as the amino source to release N2 as the single byproduct. This reaction exhibits high functional group tolerance and regioselectivity, providing a variety of 2-amino substituted indoles in high to excellent yield. The procedure is robust, reliable, and compatible with water and air.
