Biocatalytic Synthesis Towards Both Antipodes of 3-hydroxy-3-phenylpropanitrile a Precursor to Fluoxetine, Atomoxetine and Nisoxetine
Document Type
Article
Publication Date
12-31-2006
Publication Title
Tetrahedron Letters
DOI
10.1016/j.tetlet.2006.12.057
ISSN
0040-4039
Abstract
The bakers’ yeast reduction of 3-oxo-3-phenylpropanenitrile (1) has been difficult to achieve due to a dominant alkylating mechanism. A library of 20 bakers’ yeast reductases, that are overexpressed in Escherichia coli, were screened against (1). Four enzymes were found to reduce this substrate and by varying the enzyme both enantiomers of 3-hydroxy-3-phenylpropanitrile (2) could be prepared with a high enantiomeric excess. In addition, the Escherichia coli whole-cell system can be optimized to nearly eliminate the competing alkylating mechanism. By using this system, a formal biocatalytic synthesis of both antipodes of fluoxetine, atomoxetine and nisoxetine has been demonstrated.
Recommended Citation
Hammond, Richard J., Benjamin W. Poston, Ion Ghiviriga, Brent D. Feske.
2006.
"Biocatalytic Synthesis Towards Both Antipodes of 3-hydroxy-3-phenylpropanitrile a Precursor to Fluoxetine, Atomoxetine and Nisoxetine."
Tetrahedron Letters, 48 (7): 1217-1219: Elsevier.
doi: 10.1016/j.tetlet.2006.12.057 source: https://www.sciencedirect.com/science/article/pii/S0040403906025068?via%3Dihub
https://digitalcommons.georgiasouthern.edu/chem-facpubs/134
Copyright
Copyright belongs to Elsevier. Information regarding the dissemination and usage of journal articles can be accessed through the following links.Â
