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Biocatalytic Carbene Transfer Using Diazirines.

Porter NJ, Danelius E, Gonen T, Arnold FH
J Am Chem Soc 144 8892-8896 (2022)
Cited: 10 times
EuropePMC logo PMID: 35561334

Abstract

Biocatalytic carbene transfer from diazo compounds is a versatile strategy in asymmetric synthesis. However, the limited pool of stable diazo compounds constrains the variety of accessible products. To overcome this restriction, we have engineered variants of Aeropyrum pernix protoglobin (ApePgb) that use diazirines as carbene precursors. While the enhanced stability of diazirines relative to their diazo isomers enables access to a diverse array of carbenes, they have previously resisted catalytic activation. Our engineered ApePgb variants represent the first example of catalysts for selective carbene transfer from these species at room temperature. The structure of an ApePgb variant, determined by microcrystal electron diffraction (MicroED), reveals that evolution has enhanced access to the heme active site to facilitate this new-to-nature catalysis. Using readily prepared aryl diazirines as model substrates, we demonstrate the application of these highly stable carbene precursors in biocatalytic cyclopropanation, N-H insertion, and Si-H insertion reactions.

Articles - 7ute mentioned but not cited (1)

  1. Biocatalytic Carbene Transfer Using Diazirines. Porter NJ, Danelius E, Gonen T, Arnold FH. J Am Chem Soc 144 8892-8896 (2022)


Reviews citing this publication (3)

  1. MicroED in drug discovery. Danelius E, Patel K, Gonzalez B, Gonen T. Curr Opin Struct Biol 79 102549 (2023)
  2. Advances and applications of microcrystal electron diffraction (MicroED). Haymaker A, Nannenga BL. Curr Opin Struct Biol 84 102741 (2024)
  3. Recent Synthetic Advances on the Use of Diazo Compounds Catalyzed by Metalloporphyrins. Simões MMQ, Cavaleiro JAS, Ferreira VF. Molecules 28 6683 (2023)

Articles citing this publication (6)

  1. MicroED Structure of a Protoglobin Reactive Carbene Intermediate. Danelius E, Porter NJ, Unge J, Arnold FH, Gonen T. J Am Chem Soc 145 7159-7165 (2023)
  2. Protoglobin-Catalyzed Formation of cis-Trifluoromethyl-Substituted Cyclopropanes by Carbene Transfer. Schaus L, Das A, Knight AM, Jimenez-Osés G, Houk KN, Garcia-Borràs M, Arnold FH, Huang X. Angew Chem Int Ed Engl 62 e202208936 (2023)
  3. Mechanistic Insights into the Ene-Reductase-Catalyzed Promiscuous Reduction of Oximes to Amines. Breukelaar WB, Polidori N, Singh A, Daniel B, Glueck SM, Gruber K, Kroutil W. ACS Catal 13 2610-2618 (2023)
  4. Reactions of Frustrated Lewis Pairs with Chloro-Diazirines: Cleavage of N=N Double Bonds. Mandal D, Chen T, Qu ZW, Grimme S, Stephan DW. Angew Chem Int Ed Engl 61 e202209241 (2022)
  5. An artificial metalloenzyme that can oxidize water photocatalytically: design, synthesis, and characterization. Polanco EA, Opdam LV, Passerini L, Huber M, Bonnet S, Pandit A. Chem Sci 15 3596-3609 (2024)
  6. Enzymatic Nitrogen Incorporation Using Hydroxylamine. Gao S, Das A, Alfonzo E, Sicinski KM, Rieger D, Arnold FH. J Am Chem Soc 145 20196-20201 (2023)


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