Novel enzymatic reduction of α-amido- and α-cyanoalkyl-β-keto esters catalyzed by ketoreductases
| Autor: | Theodore Tyrikos-Ergas, Vasileios Giannopoulos, Ioulia Smonou, Kamela Myrtollari |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
chemistry.chemical_classification
010405 organic chemistry Process Chemistry and Technology Lactacystin 010402 general chemistry 01 natural sciences Catalysis 0104 chemical sciences Reduction (complexity) chemistry.chemical_compound Enzyme chemistry Yield (chemistry) Organic chemistry Stereoselectivity Physical and Theoretical Chemistry |
| Zdroj: | Molecular Catalysis. 490:110952 |
| ISSN: | 2468-8231 |
| DOI: | 10.1016/j.mcat.2020.110952 |
| Popis: | An enzymatic approach for the asymmetric reduction of α-amido- and α-cyanoalkyl-β-keto esters has been developed. We have shown that NADPH-dependent ketoreductases can catalyze these transformations with excellent activity and high stereoselectivity, leading to optically pure β-hydroxy-α-amido esters as well as optically pure β-hydroxy-α-cyanoalkyl esters. With this method tert-butyl 2-acetamido-3-hydroxy-4-methylpentanoate, a valuable chiral intermediate for the synthesis of lactacystin, was obtained in high yield and excellent anti-diastereoselectivity. The ketoreductase catalyzed reduction of α-cyanomethyl- and α-cyanoethyl-β-keto esters to form the corresponding optically pure β-hydroxy esters, which are chiral intermediates for the synthesis of optically pure α-substituted γ-butyro and δ-valerolactams, was accomplished in high yield and high stereoselectivity leading to one stereoisomer out of four (>99 % de, >99 % ee, >99 % conversion). |
| Databáze: | OpenAIRE |
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