Selection, Purification, Characterisation, and Cloning of a Novel Heat-Stable Stereo-Specific Amidase fromKlebsiellaoxytoca, and Its Application in the Synthesis of Enantiomerically Pure (R)- and (S)-3,3,3-Trifluoro-2-hydroxy-2-methylpropionic Acids and (S)-3,3,3-Trifluoro-2-hydroxy-2-methylpropionamide
| Autor: | Veronika Venetz, Walter Brieden, Andreas Tinschert, Jean-Paul Roduit, Nicholas M. Shaw, Thomas Zimmermann, Marie-Louise Hischier, Patricia De Riedmatten, Andrew Naughton, Evelyne Schmid, Karen Robins, Bertin Zimmermann, Roman NEUMüLLER, Josef Werlen |
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| Rok vydání: | 2002 |
| Předmět: | |
| Zdroj: | Organic Process Research & Development. 6:497-504 |
| ISSN: | 1520-586X 1083-6160 |
| DOI: | 10.1021/op020025d |
| Popis: | We isolated, characterised, and cloned an enantio-specific amidase from Klebsiella oxytoca and used it to resolve (R,S)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide, giving (R)-3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid and (S)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide. The (S)-amide could then be hydrolysed chemically to (S)-3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid. The process can therefore be adapted to produce both (R)- and (S)-enantiomers of 3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid, or (S)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide. The biocatalytic step is part of a combined chemical and biocatalytic route that starts from ethyl trifluoroacetoacetate. The products typically have a purity of greater than 98% and ee values of essentially 100% after isolation. The process has been used to produce 100-g amounts of the (S)-acid, and successfully scaled up to produce 100-kg amounts of the (R)-acid, with the biotransformation carried out at the 1500-L scale. |
| Databáze: | OpenAIRE |
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