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Synthesis of Aliphatic ( S )‐α‐Hydroxycarboxylic Amides using a One‐Pot Bienzymatic Cascade of Immobilised Oxynitrilase and Nitrile Hydratase
Author(s) -
van Pelt Sander,
van Rantwijk Fred,
Sheldon Roger A.
Publication year - 2009
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200800625
Subject(s) - hydrocyanation , chemistry , nitrile hydratase , nitrile , organic chemistry , aldehyde , lyase , aqueous solution , acetonitrile , cyanide , enzyme , catalysis
A one‐pot bienzymatic cascade combining a hydroxynitrile lyase ( Manihot esculenta , E.C. 4.1.2.10) and a nitrile hydratase ( Nitriliruptor alkaliphilus , E.C. 4.2.1.84) for the synthesis of enantiopure aliphatic α‐hydroxycarboxylic amides from aldehydes is described. Both enzymes were immobilised as cross‐linked enzyme aggregates (CLEAs). Stability tests show that the nitrile hydratase CLEAs are sensitive to water‐immiscible organic solvents as well as to aldehydes and hydrogen cyanide (HCN), but are remarkably stable and show useful activity in acidic aqueous environments of pH 4–5. The cascade reactions are consequently carried out by using a portionwise feed of HCN and moderate concentrations of aldehyde in acidic aqueous buffer to suppress the uncatalysed hydrocyanation background reaction. After optimisation, this method was used to synthesise five different kinds of aliphatic α‐hydroxycarboxylic amides from the corresponding aldehydes with good yields and with enantiomeric purities comparable to those obtained for the α‐hydroxynitriles in the microaqueous hydrocyanation using hydroxynitrile lyase and an excess of HCN.