Bienzymatic Cascade for the Synthesis of an Optically Active O-benzoyl Cyanohydrin

• Published in: Catalysts
• Main Authors: Laura Leemans, Luuk van Langen, Frank Hollmann, Anett Schallmey
• Format: Text
• Language: English
• Published: Multidisciplinary Digital Publishing Institute 2019
• Subjects: Enantioselectivity; enzyme cascade; hydroxynitrile lyase; lipase; hydrocyanation; transesterification; Antarc*; Antarctica
• Online Access: https://doi.org/10.3390/catal9060522

A concurrent bienzymatic cascade for the synthesis of optically pure (S)-4-methoxymandelonitrile benzoate ((S)-3) starting from 4-anisaldehyde (1) has been developed. The cascade involves an enantioselective Manihot esculenta hydroxynitrile lyase-catalyzed hydrocyanation of 1, and the subsequent benzoylation of the resulting cyanohydrin (S)-2 catalyzed by Candida antarctica lipase A in organic solvent. To accomplish this new direct synthesis of the protected enantiopure cyanohydrin, both enzymes were immobilized and each biocatalytic step was studied separately in search for a window of compatibility. In addition, potential cross-interactions between the two reactions were identified. Optimization of the cascade resulted in 81% conversion of the aldehyde to the corresponding benzoyl cyanohydrin with 98% enantiomeric excess.