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Biocatalytic Regio- and Stereo-Selective Alkylation of Pyrazoles for the Synthesis of β-Substituted Amino Acids
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J
DOI：10.1002/adsc.70569.png)
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Abstract
En 中文
Noncanonical amino acids (ncAAs) are valuable chiral building blocks with a broad range of applications. β-Pyrazol-1-yl-L-alanine (β-PA), a typical ncAA, is a bioactive molecule and chiral building block for pharmaceutically active agents. In this work, we have developed an enzymatic approach for highly regio- and stereo-selective pyrazole alkylation to synthesize various β-pyrazole-substituted α-amino acids. Three cysteine synthase homologous enzymes exhibited a broad substrate scope toward substituted pyrazoles and related N-heterocycles, catalyzing highly N1- or C4-selective alkylation of these nucleophiles with the α-aminoacrylate intermediate, which is a key intermediate of type II PLP-dependent enzymes. Accordingly, a variety of β-pyrazole-substituted L-alanines were synthesized with high regioselectivity (>98:2 r.r.) and enantioselectivity (up to >99:1 e.r.). Moreover, the practical utility is demonstrated by preparative biocatalytic transformations. This work not only showcases the values of biocatalysis in facile and selective synthesis of ncAAs but also offers an avenue for accessing to valuable N-alkylated pyrazole scaffolds.
Keywords:
alkylation
biocatalysis
cysteine synthase
pyrazoles
Journal
A
IF:
4
Papers:
424
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