Hydroxynitrile lyase-catalyzed addition of HCN to 4-substituted cyclohexanones: stereoselective preparation of tetronic acids

The addition of HCN to 4-alkylcyclohexanones 1 to give cyanohydrins 2 is strongly catalyzed by hydroxy-ni trile lyases (HNLs). With PaHNL, from bitter almond, trans-addition occurs almost exclusively, yielding trans-2. With MeHNL, from cassava, cis-addition is preferred to give cis-2. cis-Selectivity is nearly quantitative, especially for cyclohexanones with larger 4-substituents. Comparable results with respect to the stereoselectivity were observed in the HNL-catalyzed addition of HCN to 4-alkoxycyclohexanones 3a–g. In contrast, the stereoselectivity in the HNL-catalyzed addition to 4-alkanoyloxycyclohexanones 3h–k is very poor. The transformation of cis-4-propylcyclohexanone cyanohydrin (2c) into the corresponding cis-spirotetronic acid 7 occurs without any isomerization.Key words: enzyme, hydroxynitrile lyase, cyclohexanones, cyanohydrins, cis/trans-stereoselectivity.