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

Effenberger, Franz; Roos, Jürgen; Kobler, Christoph; Bühler, Holger
June 2002
Canadian Journal of Chemistry;Jun2002, Vol. 80 Issue 6, p671
Academic Journal
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.L'addition du HCN sur les 4-alkylcyclohexanones (1) conduisant à la formation de cyanohydrines (2) est fortement catalysée par les lyases d'hydroxynitriles (« HNL »). Sous l'influence d'une PaHNL obtenue à partir de l'amande amère, l'addition se fait pratiquement exclusivement de façon trans, conduisant aux trans-2. Avec une MeHNL tirée de cassava, l'addition se fait préférentiellement de façon cis pour conduire aux cis-2. Dans les cas de cyclohexanones portant des substituants encombrants en position 4, la sélectivité cis est pratiquement quantitative. Des résultats de stéréosélectivités comparables sont aussi obtenus lors de l'addition de HCN, catalysée par une lyase d'hydroxynitrile, aux 4-alcoxycyclohexanones (3a-g). Par opposition, la stéréosélectivité de l'addition de HCN, catalysée par une lyase d'hydroxynitrile, sur les 4-alcanoyloxycyclohexanones (3h-k) est très faible. La transformation de la cyanohydrine de la cis-4-propylcyclohexanone (2c) en acide cis-spirotétronique correspondant (7) se réalise sans épimérisation.Mots clés : enzyme, lyase d'hydroxynitrile, cyclohexanones, cyanohydrines, stéréosélectivité cis/trans.[Traduit par la Rédaction]


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