Deracemization of diastereomerically pure syn- and anti-α-substituted β-hydroxyesters by Novozyme 435 lipase and determination of their absolute configuration by NMR spectroscopy
| Autor: | Dieter Greif, Christian Trapp, Marek J. Pecyna, Corinna Herrmann, Annett Fuchs, Kateřina Barková, Martin Hofrichter |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
biology
010405 organic chemistry Process Chemistry and Technology Absolute configuration Nuclear magnetic resonance spectroscopy 010402 general chemistry biology.organism_classification 01 natural sciences Catalysis 0104 chemical sciences Acylation chemistry.chemical_compound chemistry Biocatalysis biology.protein Organic chemistry Candida antarctica Physical and Theoretical Chemistry Enantiomer Lipase Derivatization |
| Zdroj: | Molecular Catalysis. 509:111578 |
| ISSN: | 2468-8231 |
| Popis: | Enantiomerically pure α-substituted β-hydroxyesters are important chiral building blocks for ligands, auxiliaries and β-lactam antibiotics. A two-step chemo-enzymatic procedure using lipase as biocatalyst is an efficient way to synthesize such products. To date, the methods described are limited to molecules that do not contain a chiral center adjacent to the racemic carbinol, and furthermore, they are limited to acylation. Here, we investigated the deracemization of diastereomerically pure syn- and anti-α-substituted β-hydroxyesters containing two stereo centers, using experimental methods under neat conditions and classical molecule dynamics (MD) simulation. A screening of free and immobilized commercial lipases identified immobilized lipase B from Candida antarctica (Novozyme 435) as the most appropriate biocatalyst for sterically demanding α-substituted β-hydroxyesters. Using Novozyme 435, reaction conditions were optimized and hydroxyesters (3S) or (3R) were achieved with enantiomeric excesses up to ≥99% ee and maximum overall yields of 80%. The absolute configuration of the enantiomers was eventually determined by 1H-NMR spectroscopy after derivatization with Mosher's reagent (α-methoxy-α-trifluoromethylphenylacetic acid = MTPA). |
| Databáze: | OpenAIRE |
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