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 aromat ic and heteroaromatic (S)-cyanohydrins (S)-1a, c-h were obtained in ci trate buffer in good optical yields by removal of the aldehydes as hyd rogensulfite adducts. The poorly water soluble 3-phenoxybenzaldehyde c yanohydrin (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 bisul fite adduct, the ee-values of (S)-1b could be improved slightly. An en antiomeric excess >80% of (S)-1b was obtained, however, in the presenc e of Triton X100 and semicarbazide for the aldehyde capture. A further improvement was reached in the biphasic system citrate buffer/diisopr opyl ether (40:1) at 39 degrees C, addition of catalytic amounts of an iline 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 cyanohydr ins (S)-1d, e, g and h were also obtained with excellent enantiomeric excesses. In contrast the cleavage of (R,S)-butanalcyanohydrin provide d the (S)cyanohydrin after 41 h with only 70%ee.