- Engineered Enzymes Enable Selective N-Alkylation of Pyrazoles With Simple Haloalkanes
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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.
- Bengel, Ludwig L.,Aberle, Benjamin,Egler-Kemmerer, Alexander-N.,Kienzle, Samuel,Hauer, Bernhard,Hammer, Stephan C.
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supporting information
p. 5554 - 5560
(2021/02/01)
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- DERIVATIVES OF 6,7-DIHYDRO-5H-IMIDAZO[1,2-a]IMIDAZOLE-3-CARBOXYLIC ACID AMIDES
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Derivatives of 6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid amide exhibit good inhibitory effect upon the interaction of CAMs and Leukointegrins and are thus useful in the treatment of inflammatory disease.
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Page/Page column 36
(2010/12/29)
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