N-Halogenation by Vanadium-Dependent Haloperoxidases Enables 1,2,4-Oxadiazole Synthesis.

Autor: Sharma M; Department of Chemistry, Emory University, 1515 Dickey Dr, Atlanta, GA, 30322.; School of Molecular Sciences, Arizona State University, 551 E University Dr, Tempe, AZ, 85281., Patton ZE; Department of Chemistry, Emory University, 1515 Dickey Dr, Atlanta, GA, 30322., Shoemaker CR; School of Molecular Sciences, Arizona State University, 551 E University Dr, Tempe, AZ, 85281., Bacsa J; Department of Chemistry, Emory University, 1515 Dickey Dr, Atlanta, GA, 30322., Biegasiewicz KF; Department of Chemistry, Emory University, 1515 Dickey Dr, Atlanta, GA, 30322.; School of Molecular Sciences, Arizona State University, 551 E University Dr, Tempe, AZ, 85281.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Dec 09; Vol. 63 (50), pp. e202411387. Date of Electronic Publication: 2024 Oct 30.
DOI: 10.1002/anie.202411387
Abstrakt: Nitrogen-containing compounds are valuable synthetic intermediates and targets in nearly every chemical industry. While methods for nitrogen-carbon and nitrogen-heteroatom bond formation have primarily relied on nucleophilic nitrogen atom reactivity, molecules containing nitrogen-halogen bonds allow for electrophilic or radical reactivity modes at the nitrogen center. Despite the growing synthetic utility of nitrogen-halogen bond-containing compounds, selective catalytic strategies for their synthesis are largely underexplored. We recently discovered that the vanadium-dependent haloperoxidase (VHPO) class of enzymes are a suitable biocatalyst platform for nitrogen-halogen bond formation. Herein, we show that VHPOs perform selective halogenation of a range of substituted benzamidine hydrochlorides to produce the corresponding N'-halobenzimidamides. This biocatalytic platform is applied to the synthesis of 1,2,4-oxadiazoles from the corresponding N-acylbenzamidines in high yield and with excellent chemoselectivity. Finally, the synthetic applicability of this biotechnology is demonstrated in an extension to nitrogen-nitrogen bond formation and the chemoenzymatic synthesis of the Duchenne muscular dystrophy drug, ataluren.
(© 2024 Wiley-VCH GmbH.)
Databáze: MEDLINE
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