Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 61, Issue 48, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202213056
Keywords
Alkylation; Biocatalysis; Heterocycles; Methyltransferase; SAM Recycling
Categories
Funding
- Deutsche Forschungsgemeinschaft [HA 7668/2-1]
- Deutsche Bundesstiftung Umwelt [20020/690]
- Spanish MICINN (Ministerio de Ciencia e Innovacion) [PID2019-111300GA-I00]
- Ramon y Cajal program [RYC2020-028628-I]
- Spanish MIU (Ministerio de Universidades) predoctoral FPU fellowship [FPU18/02380]
- Projekt DEAL
Ask authors/readers for more resources
This study reports a new method for regioselective N-methylation of unsaturated heterocycles. By using two methyltransferases and simple reagents, important molecules with biological activities can be synthesized efficiently.
Methods for regioselective N-methylation and -alkylation of unsaturated heterocycles with off the shelf reagents are highly sought-after. This reaction could drastically simplify synthesis of privileged bioactive molecules. Here we report engineered and natural methyltransferases for challenging N-(m)ethylation of heterocycles, including benzimidazoles, benzotriazoles, imidazoles and indazoles. The reactions are performed through a cyclic enzyme cascade that consists of two methyltransferases using only iodoalkanes or methyl tosylate as simple reagents. This method enables the selective synthesis of important molecules that are otherwise difficult to access, proceeds with high regioselectivity (r.r. up to >99 %), yield (up to 99 %), on a preparative scale, and with nearly equimolar concentrations of simple starting materials.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available