Chemoenzymatic Synthesis of 2-Aryl Thiazolines from 4-Hydroxybenzaldehydes Using Vanillyl Alcohol Oxidases.
Angew Chem Int Ed Engl
; 63(30): e202405833, 2024 07 22.
Article
em En
| MEDLINE
| ID: mdl-38748747
ABSTRACT
Nitrogen heterocycles are commonly found in bioactive natural products and drugs. However, the biocatalytic tools for nitrogen heterocycle synthesis are limited. Herein, we report the discovery of vanillyl alcohol oxidases (VAOs) as efficient biocatalysts for the one-pot synthesis of 2-aryl thiazolines from various 4-hydroxybenzaldehydes and aminothiols. The wild-type biocatalyst features a broad scope of 4-hydroxybenzaldehydes. Though the scope of aminothiols is limited, it could be improved via semi-rational protein engineering, generating a variant to produce previously inaccessible cysteine-derived bioactive 2-aryl thiazolines using the wild-type VAO. Benefiting from the derivatizable functional groups in the enzymatic products, we further chemically modified these products to expand the chemical space, offering a new chemoenzymatic strategy for the green and efficient synthesis of structurally diverse 2-aryl-thiazoline derivatives to prompt their use in drug discovery and catalysis.
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Base de dados:
MEDLINE
Assunto principal:
Tiazóis
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article