Continuous enantioselective transesterification in organic solvents. Use of suspended lipase preparations in a microfiltration membrane reactor

A continuously stirred tank reactor equipped with a microfiltration membrane unit for effective retention of solid enzyme particles in organic solvent systems was constructed. A microfiltration membrane with pore size 0.1 μm based on a polypropylene matrice was used for enzyme retention and showed no loss of performance or denaturation by the organic solvent. The stereoselective transesterification reaction of (±)-trans-sobrerol with vinyl acetate as both acyl donor and solvent was chosen as a model system. Lipase PS from Pseudomonas sp. was used in its native form without further modification steps and remained active and highly stereoselective at 50 °C when applied to the reaction system for about 600 h of continuous operation. (--)-(1S,5R)-sobrerolacetate and (+)-(1R,5S)-sobrerol could be obtained in the reactor outlet stream at approximately 48% conversion with enantiomeric excesses eeP ≈ 92% and eeS≈ 80%, respectively. Furthermore, theoretical kinetic studies showed that limitations in enantiomeric purity due to the characteristics of an ideal mixed tank may be sufficiently overcome by designing a simple two-stage process.