Nitrilases Acting as Nitrile Hydratases

In conclusion, the bienzymatic transformation of aldehydes and HCN into the enantiomerically pure 2-hydroxycarboxylic acids is feasible. The stereochemistry can be steered either by the hydroxynitrile lyase or by both enzymes in combination and the hydrocyanation equilibrium is no longer an issue because it can be shifted to complete conversion. The formation of large amounts of amide, in particular (S)-4a, somewhat reduces the immediate practical value of our procedure. Ways to obviate this unwanted side-reaction will be discussed later. 

We found that nitrile hydration in the presence of PfNLase is Hkewise subject to electronic effects. Hardly any amide was formed from 2-phenylpropionitrile (Id) in the presence of this latter enzyme but the hydration pathway predominated, in contrast, with the electron-deficient 2-chloro-2-phenylacetonitrile (le) the extent 

The formation of amide by nitrilase somewhat reduces the synthetic value of our hydroxynitrile lyase-nitrUase based bienzymatic procedure for (S)-3a, as noted 

Commonly available nitrilases hydrolyze cyanohydrins with modest to excellent selectivity for the (R)-enantiomer. The formation of amide coproducts, once thought to be an insignificant side-reaciion, varies erratically in cyanohydrin hydrolysis between minute and copious, depending on the enzyme and the steric character of the nitrile. 

The bienzymatic transformation of aldehydes and HCN in the presence of an oxynitrilase and a nitrilase is a useful addition to the synthetic repertoire, provided that the coproduction of amide can be avoided. 

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