Engineered enzymes enable selective N‐alkylation of pyrazoles with simple haloalkanes

Bengel LL, Aberle B, Egler-Kemmerer A-N, Kienzle S, Hauer B, Hammer S (2021)
Angewandte Chemie International Edition 60(10): 5554-5560.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
Download
Es wurden keine Dateien hochgeladen. Nur Publikationsnachweis!
Autor*in
Bengel, Ludwig L.; Aberle, Benjamin; Egler-Kemmerer, Alexander-N.; Kienzle, Samuel; Hauer, Bernhard; Hammer, StephanUniBi
Abstract / Bemerkung
Selective alkylation of pyrazoles could solve a challenge in chemistry and streamline synthesis of important molecules. Here we report catalyst‐controlled pyrazole alkylation by a cyclic two‐enzyme cascade. In this enzymatic system, a promiscuous enzyme uses haloalkanes as precursors to generate non‐natural analogs of the common cosubstrate S‐adenosyl‐l‐methionine. A second engineered enzyme transfers the alkyl group in highly selective C−N bond formations to the pyrazole substrate. The cosubstrate is recycled and only used in catalytic amounts. Key is a computational enzyme‐library design tool that converted a promiscuous methyltransferase into a small enzyme family of pyrazole‐alkylating enzymes in one round of mutagenesis and screening. With this enzymatic system, pyrazole alkylation (methylation, ethylation, propylation) was achieved with unprecedented regioselectivity (>99 %), regiodivergence, and in a first example on preparative scale.
Erscheinungsjahr
2021
Zeitschriftentitel
Angewandte Chemie International Edition
Band
60
Ausgabe
10
Seite(n)
5554-5560
ISSN
1433-7851
eISSN
1521-3773
Finanzierungs-Informationen
Open-Access-Publikationskosten wurden durch die Universität Bielefeld im Rahmen des DEAL-Vertrags gefördert.
Page URI
https://pub.uni-bielefeld.de/record/2949714

Zitieren

Bengel LL, Aberle B, Egler-Kemmerer A-N, Kienzle S, Hauer B, Hammer S. Engineered enzymes enable selective N‐alkylation of pyrazoles with simple haloalkanes. Angewandte Chemie International Edition. 2021;60(10):5554-5560.
Bengel, L. L., Aberle, B., Egler-Kemmerer, A. - N., Kienzle, S., Hauer, B., & Hammer, S. (2021). Engineered enzymes enable selective N‐alkylation of pyrazoles with simple haloalkanes. Angewandte Chemie International Edition, 60(10), 5554-5560. https://doi.org/10.1002/anie.202014239
Bengel, L. L., Aberle, B., Egler-Kemmerer, A. - N., Kienzle, S., Hauer, B., and Hammer, S. (2021). Engineered enzymes enable selective N‐alkylation of pyrazoles with simple haloalkanes. Angewandte Chemie International Edition 60, 5554-5560.
Bengel, L.L., et al., 2021. Engineered enzymes enable selective N‐alkylation of pyrazoles with simple haloalkanes. Angewandte Chemie International Edition, 60(10), p 5554-5560.
L.L. Bengel, et al., “Engineered enzymes enable selective N‐alkylation of pyrazoles with simple haloalkanes”, Angewandte Chemie International Edition, vol. 60, 2021, pp. 5554-5560.
Bengel, L.L., Aberle, B., Egler-Kemmerer, A.-N., Kienzle, S., Hauer, B., Hammer, S.: Engineered enzymes enable selective N‐alkylation of pyrazoles with simple haloalkanes. Angewandte Chemie International Edition. 60, 5554-5560 (2021).
Bengel, Ludwig L., Aberle, Benjamin, Egler-Kemmerer, Alexander-N., Kienzle, Samuel, Hauer, Bernhard, and Hammer, Stephan. “Engineered enzymes enable selective N‐alkylation of pyrazoles with simple haloalkanes”. Angewandte Chemie International Edition 60.10 (2021): 5554-5560.
Alle Dateien verfügbar unter der/den folgenden Lizenz(en):
Creative Commons Namensnennung 4.0 International Public License (CC-BY 4.0):
Link(s) zu Volltext(en)
Access Level
OA Open Access

Export

Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®

Quellen

PMID: 33300646
PubMed | Europe PMC

Suchen in

Google Scholar