Enzyme and Reaction Engineering in Biocatalysis: Synthesis of (S)-Methoxyisopropylamine (= (S)-1-Methoxypropan-2-amine)

Abstract

Methoxyisopropylamine is a chiral amine moiety common to the chemical structures of two important chloroacetamide herbicides, metolachlor and dimethenamid. The activity of both products lies predominantly in their (S)-enantiomeric forms. Celgro scientists have developed a high-productivity biocatalytic process to (S)-methoxyisopropylamine via transamination of methoxyacetone and isopropylamine. Biocatalyst and process optimization was achieved by integration of molecular biology, fermentation, enzymology, and engineering disciplines to identify and overcome kinetic, stability, and thermodynamic constraints on productivity. The result was a 50° vacuum reaction producing 2M (S)-methoxyisopropylamine (18 wt-%) at >99% ee, with 97% conversion of methoxyacetone in 7 h, meeting economic targets applicable to agrochemical manufacturing.