Bienzymatic cascade for the synthesis of an optically active O-benzoyl cyanohydrin

• Published in: Catalysts
• Main Authors: Leemans, Laura (author), van Langen, Luuk (author), Hollmann, F. (author), Schallmey, Anett (author)
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2019
• Subjects: Enantioselectivity; Enzyme cascade; Hydrocyanation; Hydroxynitrile lyase; Lipase; Transesterification; Antarc*; Antarctica
• Online Access: http://resolver.tudelft.nl/uuid:d9ef81e7-baae-4c8c-8962-a2e66cc2b049; 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. BT/Biocatalysis