Vanessa Erdmann, T. Sehl, Ilona Frindi-Wosch
Jul 2, 2019
Citations
0
Influential Citations
21
Citations
Journal
ACS Catalysis
Abstract
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...