Optimization of 2-alkoxyacetates as acylating agent for enzymatic kinetic resolution of chiral amines
| Autor: | Márk Oláh, Gábor Hornyánszky, László Poppe, Daniel L. Kovacs, Gabriel Katona |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
biology
010405 organic chemistry Chemistry Organic Chemistry 010402 general chemistry biology.organism_classification 01 natural sciences Biochemistry Medicinal chemistry 0104 chemical sciences Catalysis Kinetic resolution Acylation Homologous series chemistry.chemical_compound Drug Discovery Candida antarctica Enantiomer Enantiomeric excess Isopropyl |
| Zdroj: | Tetrahedron. 74:3663-3670 |
| ISSN: | 0040-4020 |
| DOI: | 10.1016/j.tet.2018.05.032 |
| Popis: | In this study, the activity of acetic acid esters modified with electron withdrawing 2-alkoxy-groups was investigated as acylating agent in kinetic resolution (KR) of racemic amines. A homologous series of the isopropyl esters of four 2-alkoxyacetic acids (2-methoxy-, 2-ethoxy-, 2-propoxy- and 2-butoxyacetic acids) were prepared and investigated for enantiomer selective N-acylation, catalyzed by lipase B from Candida antarctica, under batch and continuous-flow conditions. In the first set of experiments, isopropyl 2-propoxyacetate showed the highest effectivity with all of the four racemic amines [(±)-1-phenylethylamine, (±)-4-phenylbutan-2-amine, (±)-heptan-2-amine and (±)-1-methoxypropane-2-amine] in the set enabling excellent conversions (≥46%) and enantiomeric excess values (ee ≥ 99%) with each amines in continuous-flow mode KRs under the optimized reaction conditions. In a second set of experiments, KRs of five additional amines – being substituted derivatives of (±)-1-phenylethylamine – further demonstrated the usefulness of isopropyl 2-propoxyacetate – being the best acylating agent in the first set of KRs – in KRs leading to (R)-N-propoxyacetamides with high ee values (≥99.8%). |
| Databáze: | OpenAIRE |
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