Development of a continuously operating process for the enantioselective synthesis of a b-amino acid ester via a solvent-free chemoenzymatic reaction sequence

A sequential, chemoenzymatic process for a continuously operating production of the chiral β-amino acid ester ethyl (S)-3-(benzylamino)- butanoate was developed. The reactor set-up combined a plug-flow reactor for the thermal aza-Michael addition of benzylamine to trans-ethyl crotonate coupled to a subsequent packed-bed reactor for the lipase (Novozym 435)-catalyzed kinetic resolution of the racemic intermediate product, which was formed in the initial step. The coupled reactors were operated continuously for a time period of 4 days without significant loss of enzyme activity. The target β-amino acid ester was obtained with 92% conversion in the plug-flow reactor and 59% conversion in the packed bed reactor at high enantiomeric excess of >98%. A space-time yield of 0.4 kgL-1d-1 was calculated for the total reactor system and 1.8 kgL-1d-1 based solely on the volume of the packed bed reactor. A total turnover number of 158,000 was calculated for the biocatalyst assuming the same deactivation rate as observed in batch experiments. The continuously operating, solvent-free process thus represents an efficient method for the enantioselective production of a value added (S)-β-amino acid ester starting from cheap substrates. © 2013 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim.

Subjects

β-amino acids

Biocatalysis

Chemoenzymatic reaction sequence

Continuously operating process

Kinetic resolution

Solvent-free conditions

DDC Class

570: Biowissenschaften, Biologie

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Development of a continuously operating process for the enantioselective synthesis of a b-amino acid ester via a solvent-free chemoenzymatic reaction sequence