Methoxamine Synthesis in a Biocatalytic 1-Pot 2-Step Cascade Approach
| Autor: | Wolfgang Kroutil, Robert C. Simon, Dörte Rother, Vanessa Erdmann, Ilona Frindi-Wosch, Torsten Sehl |
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| Rok vydání: | 2019 |
| Předmět: |
010405 organic chemistry
Alcohol General Chemistry 010402 general chemistry 01 natural sciences Combinatorial chemistry Catalysis Methoxamine 0104 chemical sciences Transaminase chemistry.chemical_compound Cascade reaction chemistry Biocatalysis medicine Enantiomeric excess Amination Pyruvate decarboxylase medicine.drug |
| Zdroj: | ACS Catalysis. 9:7380-7388 |
| ISSN: | 2155-5435 |
| DOI: | 10.1021/acscatal.9b01081 |
| Popis: | Due to its function as a vasopressor, the vicinal amino alcohol methoxamine is a potential candidate for the treatment of hypotension and incontinence or has applications in ophthalmology. In this study, a biocatalytic method was developed to produce each of the four stereoisomers of methoxamine in a sequential 1-pot 2-step cascade reaction, starting from readily available pyruvate and 2,5-dimethoxybenzaldehyde without intermediate isolation. All four isomers are accessible with high conversions and very good stereoselectivities through the modular combination of carboligases and transaminases with high stereoselectivities. The development of these cascades was made possible, among other factors, by the integration of a recently engineered triple variant of the pyruvate decarboxylase from Acetobacter pasteurianus (ApPDC-E469G-I468A-W543F), which provided access to the intermediate (S)-1-hydroxy-1-(2,5-dimethoxyphenyl)propan-2-one with a high enantiomeric excess of 98%. For the amination of these stericall... |
| Databáze: | OpenAIRE |
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