1706-46-3Relevant articles and documents
Engineered Enzymes Enable Selective N-Alkylation of Pyrazoles With Simple Haloalkanes
Bengel, Ludwig L.,Aberle, Benjamin,Egler-Kemmerer, Alexander-N.,Kienzle, Samuel,Hauer, Bernhard,Hammer, Stephan C.
, p. 5554 - 5560 (2021)
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.
