Reaction temperature optimization procedure for the synthesis of (R)-mandelonitrile by Prunus amygdalus hydroxynitrile lyase using a process model approach
“…The mass transfer limitation model was developed while studying the synthesis of the (R)-cyanohydrin of benzaldehyde in an aqueous-organic two-liquid system (Gerrits et al, 2001a;Willeman et al, 2002b). It was also applied successfully to convert more difficult substrates such as 3-butenal, 4-pentenal, 5-hexenal, trans-cinnamic aldehyde, 2-hydroxybenzaldehyde, and 4-hydroxybenzaldehyde (Gerrits et al, 2001a,b;Willeman et al, 2002c).…”
Enzymes acting in a biphasic liquid of water and organic solvent may show catalytic activity dependent on the amount of phase interface available. Such an effect may be caused by several mechanisms. For example, for hydroxynitrile lyase from Prunus amygdalus, substrate mass transfer limitation has been advocated, but also adsorption of the enzyme on the interface. In this commentary it is shown that often these two mechanisms will have qualitatively similar consequences. The reaction rate will be influenced by the organic substrate concentration, by the initial enzyme concentration, and by the volume-specific interfacial area, and these influences will be linear at low values but reach a saturation level at high values. To rule out any of the models, their quantitative mathematical descriptions should be compared, taking into account that both models may be valid simultaneously.
“…The mass transfer limitation model was developed while studying the synthesis of the (R)-cyanohydrin of benzaldehyde in an aqueous-organic two-liquid system (Gerrits et al, 2001a;Willeman et al, 2002b). It was also applied successfully to convert more difficult substrates such as 3-butenal, 4-pentenal, 5-hexenal, trans-cinnamic aldehyde, 2-hydroxybenzaldehyde, and 4-hydroxybenzaldehyde (Gerrits et al, 2001a,b;Willeman et al, 2002c).…”
Enzymes acting in a biphasic liquid of water and organic solvent may show catalytic activity dependent on the amount of phase interface available. Such an effect may be caused by several mechanisms. For example, for hydroxynitrile lyase from Prunus amygdalus, substrate mass transfer limitation has been advocated, but also adsorption of the enzyme on the interface. In this commentary it is shown that often these two mechanisms will have qualitatively similar consequences. The reaction rate will be influenced by the organic substrate concentration, by the initial enzyme concentration, and by the volume-specific interfacial area, and these influences will be linear at low values but reach a saturation level at high values. To rule out any of the models, their quantitative mathematical descriptions should be compared, taking into account that both models may be valid simultaneously.
“…The nonenzymatic reaction is further suppressed by maintaining the pH in the acidic range , It is obvious that increasing the enzyme loading and reducing the aqueous phase volume will increase the competitiveness of the enzymatic reaction and improve the enantiomeric purity of the product. 1 Competition of enzymatic and uncatalyzed hydrocyanation. …”
[Reaction: see text] The (R)-oxynitrilase from almonds was immobilized as a cross-linked enzyme aggregate (CLEA) via precipitation with 1,2-dimethoxyethane and subsequent cross-linking using glutaraldehyde. The resulting preparation was a highly effective hydrocyanation catalyst under microaqueous conditions, which suppress the nonenzymatic background reaction. The beneficial effect of these latter conditions on the hydrocyanation of slow-reacting aldehydes is demonstrated. The oxynitrilase CLEA was recycled 10 times without loss of activity.
“…Furthermore, decreasing the reaction temperature should reduce the rate of the nonenzymatic hydrocyanation of 4-anisaldehyde to a higher extent than the enzymatic reaction, which would also contribute to increase the enantiomeric excess (e.e.) of the cyanohydrin [32][33][34]. Finally, the reaction must be performed at a rather low temperature, since the boiling point of HCN is 25.6 • C [35].…”
Section: Influence Of Reaction Temperaturementioning
A concurrent bienzymatic cascade for the synthesis of optically pure (S)-4-methoxymandelonitrile benzoate ((S)-3) starting from 4-anisaldehyde (1) has been developed. The cascade involves an enantioselective Manihot esculenta hydroxynitrile lyase-catalyzed hydrocyanation of 1, and the subsequent benzoylation of the resulting cyanohydrin (S)-2 catalyzed by Candida antarctica lipase A in organic solvent. To accomplish this new direct synthesis of the protected enantiopure cyanohydrin, both enzymes were immobilized and each biocatalytic step was studied separately in search for a window of compatibility. In addition, potential cross-interactions between the two reactions were identified. Optimization of the cascade resulted in 81% conversion of the aldehyde to the corresponding benzoyl cyanohydrin with 98% enantiomeric excess.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
