Organic Process Research and Development p. 1117 - 1122 (2013)
Update date:2022-08-29
Topics:
Meadows, Rebecca E.
Mulholland, Keith R.
Schuermann, Martin
Golden, Michael
Kierkels, Hans
Meulenbroeks, Elise
Mink, Daniel
May, Oliver
Squire, Christopher
Straatman, Harrie
Wells, Andrew S.
Screening of 60 transaminases using three different amine donors found that the ω-transaminase from Vibrio fluvialis together with (S)-α-methylbenzylamine to be the most promising combination to deliver the desired (S)-1-(5-fluoropyrimidin-2-yl)-ethylamine (2) in almost quantitative conversion. The process was further improved by the addition of immiscible organic solvents with toluene identified as most suitable concerning the distribution of the reactants without negatively impacting the performance of the biocatalyst. Further process optimization using commercial enzyme preparations of V. fluvialis led to product/catalyst ratios of 15 g/g cell dry weight. This approach led to a process that provided (S)-1-(5-fluoropyrimidin-2- yl)ethylamine (2) in 77% yield with 99.8% ee. In addition, a recombinant E. coli-based whole-cell biocatalyst was also designed and applied to this process. The use of this low cost enzyme formulation gave product of similar quality to that obtained using the commercial formulation of V. fluvialis. This process was further optimized and scaled-up to deliver (S)-1-(5-fluoropyrimidin-2-yl) ethylamine (2)with a yield of 66% and an optical purity of 97.3% ee. These results confirm the efficiency and competitiveness of the transaminase technology for the production of chiral amines.
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