Metal Substitution Modulates the Reactivity and Extends the Reaction Scope of Myoglobin Carbene Transfer Catalysts. Issue 12 (15th May 2017)

• Record Type: Journal Article
• Authors: Sreenilayam, Gopeekrishnan; Moore, Eric J.; Steck, Viktoria; Fasan, Rudi
• Is Part Of: Advanced synthesis & catalysis. Volume 359:Issue 12(2017)
• Page Start: 2076
• Page End: 2089
• Publication Date: 2017-05-15
• Subjects: artificial metalloenzymes -- biocatalysis -- carbene transfer -- C–H carbene insertion -- myoglobin -- protein engineering; Catalysis -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Chemistry -- Periodicals; Chemistry, Technical -- Periodicals; Chemistry -- Periodicals; Catalysis -- Periodicals; Technology, Pharmaceutical -- Periodicals; 547.2
• DOI: 10.1002/adsc.201700202
• Languages: English
• ISSNs: 1615-4150

Abstract

Abstract: Engineered myoglobins have recently emerged as promising scaffolds for catalyzing carbene‐mediated transformations. In this work, we investigated the effect of altering the metal center and first‐sphere coordination residue on the carbene transfer reactivity of myoglobin. To this end, we first established an efficient protocol for the recombinant expression of myoglobin variants incorporating metalloporphyrins with non‐native metals, including second‐ and third‐row transition metals (ruthenium, rhodium, iridium). Characterization of the cofactor‐substituted myoglobin variants across three different carbene transfer reactions (cyclopropanation, N–H insertion, S–H insertion) revealed a major influence of the nature of the metal center, its oxidation state and first‐sphere coordination environment on the catalytic activity, stereoselectivity, and/or oxygen tolerance of these artificial metalloenzymes. In addition, myoglobin variants incorporating manganese‐ or cobalt‐porphyrins were found capable of catalyzing an intermolecular carbene C–H insertion reaction involving phthalan and ethyl α‐diazoacetate, a reaction not supported by iron‐based myoglobins and previously accessed only using iridium‐based (bio)catalysts. These studies demonstrate how modification of the metalloporphyrin cofactor environment provides a viable and promising strategy to enhance the catalytic properties and extend the reaction scope of myoglobin‐based carbene transfer catalysts. Abstract :