Download Enzymatic cascade reaction for the synthesis of an imino

25th Croatian meeting of chemists and chemical engineers, Poreč, 2017.
Enzymatic cascade reaction for the synthesis of an imino aldol adduct: oxidoreduction coupled with aldol addition
Enzimatska kaskadna reakcija sinteze imino aldolnog produkta: oksidoredukcija i aldolna adicija
Morana Česnik,1 Martina Sudar,1 Đurđa Vasić-Rački,1 Pere Clapés,2 Zvjezdana Findrik
Blažević1
1
Faculty of Chemical Engineering and Technology, University of Zagreb, Croatia
2
Catalonia Institute for Advanced Chemistry, Barcelona, Spain
E-mail: [email protected]
Aldol adducts containing amino groups are important building blocks of many naturally
occurring molecules such as iminosugars [1]. In this work the oxidation of the amino alcohol
catalyzed by alcohol dehydrogenase was coupled with aldol addition catalyzed by an
aldolase, to synthesize an imino aldol adduct. The reaction scheme is presented in Figure 1.
Similar reaction system was found to be effective in our previous work [2].
Several enzymes were tested as catalysts for oxidation of Cbz-N-3-amino-1,2propanediol to Cbz-N-3-amino-2-hydroxypropanal and it is confirmed that alcohol
dehydrogenase from horse liver is the most efficient catalyst for this reaction step. Aldol
addition is catalyzed by D-fructose 6-phosphate aldolase as the most appropriate catalysts
for this reaction, according to the literature [3]. Since alcohol dehydrogenase requires a
coenzyme for its activity, the regeneration was done by using NADH oxidase. Coenzyme
regeneration has to be fast and efficient to shift the equilibrium of oxidation towards
aldehyde synthesis. Therefore, the influence of NADH oxidase and alcohol dehydrogenase
activity ratio was tested on alcohol conversion in a cascade reaction. Also, the influence of
coenzyme concentration and initial substrate (amino alcohol) concentration on the cascade
reaction product yield was examined. The operational stability of all enzymes was
determined by following their activity during the experiments.
Figure 1: Cascade reaction scheme.
References
[1] M. Gutierrez, T. Parella, J. Joglar, J. Bujons and P. Clapes, Chem. Commun. 47 (2011) 5762–5764.
[2] M. Sudar, Z. Findrik, Đ. Vasić-Rački, A. Soler and P. Clapés, RSC Adv. 5 (2015) 69819–69828.
[3] A. L. Concia, C. Lozano, J. A. Castillo, T. Parella, J. Joglar and P. Clapes, Chem. Eur. J. 15 (2009) 3808
– 3816.
Project CARBAZYMES-This project has received funding from the European Union’s Horizon 2020 research and
innovation programme under grant agreement No 635595.