Abstract
An industrial-scale stereo-selective enzymatic oxidation process for the conversion of pyrmetazole to esomeprazole was developed and optimized. Slurry-to-slurry stages are highly demanding synthetic operations due to several deteriorating factors: competing equilibria, mass transfer limitations and long-term bio-catalytic activity. Challenging characteristics of this bio-oxidation included foaming, thickening, continuous dynamic changes in viscosity, mass transport, and bio-catalyst inactivation. By screening pH, optimization of reactant loading ratios, and modification of control, crucial production attributes of materials, such as substrate particle size, were controlled and better batch-to-batch stability and scale-up was achieved.
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