Synthesis of Chiral Cyanohydrins Using Hydroxy Nitrile Lyases HNLs

Synthesis of Chiral Cyanohydrins Using Hydroxy Nitrile Lyases (HNLs) 

The reason why these enzymes have received considerable attention over the years is that they display a high degree of enantiotopic selectivity on the prochiral aldehyde and ketone substrates. The selectivity of these enzymes is in many instances masked by the rate of spontaneous racemization of the cyanohydrins, which are prone to racemization under non-acidic conditions. This balance of selectivity of the enzymes versus the competition with the spontaneous racemization reaction as a function of the pH was described as early as 1921 using the hydroxynitrile lyase enzyme from peach leaves [22], These early experiments describe one of the challenges of applying hydroxynitrile lyases on an industrial scale. 

So far HNLs from more than 11 cyanogenic plants have been characterized. Nature has evolved (R)- and (S)-selective HNLs, in contrast to other enzymes (for instance lipases) which act only on one stereoisomer. Interestingly, some enzymes, for example the one from Hevea brasiliensis, show pronounced stereoselectivity in the cyanohydrin formation, although their natural substrate is symmetric (acetone cyanohydrin) and their natural task is cyanohydrin cleavage. 

The structures of HNLs from several plant species have been elucidated, giving insight into the respective mechanisms of cyanohydrin formation. The origin of these enzymes and thus the mechanisms of their action differ widely. The (S)-HNL from Hevea brasiliensis has a catalytic triad in its active center, which effects deprotonation of HCN and site-selective attack of CN to the substrate, which is fixed in the active site. In contrast, the HNL from Prunus amygdalus is a flavo-en-zyme. However, the role of the flavin group in the catalytic cycle is unclear. The present hypothesis states that the enzyme seems to act via electrostatic change of 

Natural source Recombinant source Chirality of cyanohydrin 

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