Preparation of (S)-cyanohydrins by enantioselective cleavage of racemic cyanohydrins with (R)-hydroxynitrile lyase

The preparation of (S)-cyanohydrins (S)-1 by (R)-hydroxynitrile lyase (PaHNL) catalyzed enantioselective cleavage of racemic cyanohydrins (R,S)-1 under removal of the aldehydes released is described. The aromatic and heteroaromatic (S)-cyanohydrins (S)-1 a, c-h were obtained in citrate buffer in good optical yields by removal of the aldehydes as hydrogensulfite adducts. The poorly water soluble 3-phenoxybenzaldehyde cyanohydrin (R,S)-1b, however, gave (S)-1b only with very low ee-values under these conditions. By addition of solubilizers DMSO, triethylene glycol or Triton X100 and removal of phenoxybenzaldehyde as the bisulfite adduct, the ee-values of (S)-1b could be improved slightly. An enantiomeric excess >80% of (S)-1b was obtained, however, in the presence of Triton X100 and semicarbazide for the aldehyde capture. A further improvement was reached in the biphasic system citrate buffer/diisopropyl ether (40:1) at 39 degree C, addition of catalytic amounts of aniline and semicarbazide for aldehyde capture. Under these conditions (S)-1b could be obtained with 91%ee at 50% conversion. In the biphasic system with removal of the aldehydes as semicarbazones 3 the cyanohydrins (S)-1d, e, g and h were also obtained with excellent enantiomeric excesses. In contrast the cleavage of (R,S)-butanalcyanohydrin provided the (S)-cyanohydrin after 41 h with only 70%ee.