Preparation and Reactions of Optically Active Cyanohydrins Derived from 4- Chlorobenzaldehyde, Cyclohexanone and 2- Methylcyclohexanone using the (R) Hydroxynitrile lyase from Prunus amygdalus

doi:10.21608/ejchem.2010.1262

Preparation and Reactions of Optically Active Cyanohydrins Derived from 4- Chlorobenzaldehyde, Cyclohexanone and 2- Methylcyclohexanone using the (R) Hydroxynitrile lyase from Prunus amygdalus

10.21608/ejchem.2010.1262

Abstract

CYANURATION of 4-chlorobenzaldehyde (1), cyclohexanone (2a) and 2-methylcyclo- hexanone (2b) yielded the racemic 2-hydroxy-2-(4-chlorophenyl)ethanenitrile (R,S)-3, cyclohexanone cyanohydrin 21a and (R,S)-2-methylcyclohexanone cyanohydrin (R,S)-21b. The same reaction can be completed by using acetone cyanohydrin (4) as a transcyanating agent. The optically active cyanohydrins (R)-3 and (R)-21b could be respectively obtained by hydrocyanation of 1 and 2b using (R)-hydroxynitrile lyase (R) PaHNL [EC 4.1.2.10] from almonds (Prunus amygdalus) as a chiral catalyst. Cyanohydrins 3 and 21 in their racemic and optically active forms undergo a number of transformations which involve either the hydroxyl group or the cyanide function. Moreover, derivatization of 3 and 21b with (S)-Naproxen chloride (S)-7 gave the respective diastereoisomers 8 and 22b. The optical activities of (R)-3 and 21b as well as their derivatives were recorded. The postulated structures of the new products were supported with compatible elementary and spectroscopic (IR, 1H NMR, 13C NMR, MS and X-ray crystallography) analyses. The antitumor activity of some selected racemic new products and their respective optically active analogues were undertaken. The structure-activity relationship (SAR) was also discussed.

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