Although considerable progress has been made in metal-catalyzed preparations of non-racemic cyanohydrins, the HNL-catalyzed reaction is still the most important method for the synthesis of chiral cyanohydrins, especially for large-scale reactions. The usefulness of HNLs as catalysts for the stereoselective addition of HCN to carbonyl compounds has increased substantially because (R)-PaHNL
from almonds and two recombinant (S)-HNLs, MeHNL from M. esculenta and HbHNL from H. brasiliensis, are fairly stable and nowadays easily available in large amounts.
During the last 15 years the 3D structures of the most important HNLs have been determined. Combining the X-ray structure information with the kinetics of certain mutants of the active site made it possible to elucidate unambiguously the mechanism of cyanogenesis for both MeHNL and HbHNL, respectively. It is possible to improve yields and stereoselectivity of HNL-catalyzed formations of chiral cyanohydrins in a straightforward manner through the knowledge of the active site and the possibility of applying more reactive mutants.
Most of the stereoselective follow-up reactions of non-racemic cyanohydrins have been investigated only conceptually so far. Starting from (R)-cyanohydrins, (R)-2-hydroxy carboxylic acids, (R)-2-hydroxy aldehydes, (1R)-2-amino alcohols and (1R, 2S)-2-amino alcohols are easily available in high optical yields and chemical yields by chemical transformations of the cyano group. Analogous reactions are possible starting from (S)-cyanohydrins. Sulfonylation of the hydroxy group in non-racemic cyanohydrins subsequently allows nucleophilic substitution of the sulfonate group with complete inversion of configuration. By this means, non-racemic 2-azido nitriles, 2-amino nitriles, 1,2-diamines and 2-sulfanyl nitriles can be prepared in high optical yields. The HNL-catalyzed addition of HCN to 4-substituted cyclohexanones unexpectedly exhibits high cis/trans-selectivity, which is very useful for the stereoselective synthesis of natural products. Therefore, applications of chiral cyanohydrins for the preparation of biologically active compounds with stereogenic centers, which are applied as pharmaceuticals or plant-protecting agents, will play a major role in future developments.
Was this article helpful?