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High Regio‐ and Stereoselective Multi‐enzymatic Synthesis of All Phenylpropanolamine Stereoisomers from β‐Methylstyrene
Author(s) -
Corrado Maria L.,
Knaus Tanja,
Mutti Francesco G.
Publication year - 2021
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202100123
Subject(s) - stereoselectivity , chemistry , phenylpropanolamine , selectivity , alcohol dehydrogenase , stereochemistry , diol , biocatalysis , enzyme , transaminase , monooxygenase , combinatorial chemistry , cytochrome p450 , organic chemistry , reaction mechanism , catalysis , chromatography
We present a one‐pot cascade for the synthesis of phenylpropanolamines (PPAs) in high optical purities ( er and dr up to >99.5 %) and analytical yields (up to 95 %) by using 1‐phenylpropane‐1,2‐diols as key intermediates. This bioamination entails the combination of an alcohol dehydrogenase (ADH), an ω‐transaminase (ωTA) and an alanine dehydrogenase to create a redox‐neutral network, which harnesses the exquisite and complementary regio‐ and stereo‐selectivities of the selected ADHs and ωTAs. The requisite 1‐phenylpropane‐1,2‐diol intermediates were obtained from trans‐ or cis ‐β‐methylstyrene by combining a styrene monooxygenase with epoxide hydrolases. Furthermore, in selected cases, the envisioned cascade enabled to obtain the structural isomer (1 S ,2 R )‐1‐amino‐1‐phenylpropan‐2‐ol in high optical purity ( er and dr >99.5 %). This is the first report on an enzymatic method that enables to obtain all of the four possible PPA stereoisomers in great enantio‐ and diastereo‐selectivity.