Enzyme Catalysed Cyanohydrins Reactions

Scheme 3. Principal reaction sequence of enzyme catalysed cyanohydrin formation...

Both syntheses were done at 55 °C and the total reaction and purification took approximately 40 minutes. An enzyme catalysed cyanohydrin reduction was also investigated using two different enzymes. Although the enzyme catalysed reactions gave products of high optical purity, they did not improve the final yield, which was between one and two percent. The compounds were, however, formed with radiochemical purities of > 98%. 

A method of employing an organic solvent as a reaction medium that incorporates the safe transfer of HCN would be of great advantage to cyanohydrin production. Thus the recent development of enzyme catalysed transhydrocyanation, which employs acetone cyanohydrin [80-84] as a HCN carrier, is of significant value. This method makes the handling process of HCN both easier and less dangerous. 

Keywords Cyanogenesis, Enantioselective syntheses. Cyanohydrins, Enzyme catalysed reactions. 

Other possibilities to prepare chiral cyanohydrins are the enzyme catalysed kinetic resolution of racemic cyanohydrins or cyanohydrin esters [107 and references therein], the stereospecific enzymatic esterification with vinyl acetate [108-111] (Scheme 2) and transesterification reactions with long chain alcohols [107,112]. Many reports describe the use of fipases in this area. Although the action of whole microorganisms in cyanohydrin resolution has been described [110-116],better results can be obtained by the use of isolated enzymes. Lipases from Pseudomonas sp. [107,117-119], Bacillus coagulans [110, 111], Candida cylindracea [112,119,120] as well as lipase AY [120], Lipase PS [120] and the mammalian porcine pancreatic lipase [112, 120] are known to catalyse such resolution reactions. 

These two methods involve the potential release of toxic HCN during the reaction and a cleaner as well as a safer method is to use acetone cyanohydrin 128 as a cyanide transfer reagent. The enzyme from the Brazilian rubber tree Hevea brasiliensis, called a hydroxynitrile lyase, catalyses cyanohydrin formation from aliphatic as well as aromatic aldehydes.40... 

The pH value has an influence not only on the activity of enzymes but also on chemical reactions. The chemical cyanohydrin reaction is base-catalysed, as, compared to HCN, the cyanide ion more easily attacks the carbonyl group. As a result, a distinct decrease of the reaction rate for the non-enzymatic synthesis of mandeloni-trile occurs at lower pH values. Also, the enzyme activity decreases but not to the same extent therefore, the enantioselective enzymatic reaction becomes dominant at lower pH (see Fig. 7-11). 

The lyases comprise enzyme class 4. They are enzymes cleaving C-C, C-0, C-N and other bonds by elimination, not by hydrolysis or oxidation. Lyases also catalyse addition to donble bonds. The types of reactions catalysed by lyases are decarboxylation (decarboxylase), hydration/dehydration (hydratase/dehydratase), ammonia addition/deamination (ammonia-lyase), cyanohydrin formation/cleavage (oxynitrilase),... 

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