A multi-step biocatalytic approach for the continuous generation and use of HCN towards chiral O-acetylcyanohydrins

• Main Authors: B. Musio, A. Brahma, U. Ismayilova, N. Nikbin, S. B. Kamptmann, P. Siegert, G. E. Jeromin, S. V. Ley, M. Pohl
• Other Authors: Musio, B., Brahma, A., Ismayilova, U., Nikbin, N., Kamptmann, S. B., Siegert, P., Jeromin, G. E., Ley, S. V., Pohl, M.
• Format: Conference Object
• Language: English
• Published: 2018
• Subjects: Archer; Strompen; Wever; Antarc*; Antarctica
• Online Access: http://hdl.handle.net/11589/223806

Continuous processing technologies have been shown to be a powerful concept in order to tune reaction conditions in a very precise manner, enhance the sustainability and facilitate the scale-up of the chemical processes involving hazardous reagents. This becomes even more important during those multi-step approaches, where the use of modular components for the downstream processing together with automated in-line analytics allow the control and coordination of all the stages of the processes. In spite of these advantages, surprisingly few applications to multi-step biocatalytic strategies in flow1 have been reported so far in contrast to discrete single-step biotransformations.2 The advantages of the continuous flow technology will be described with regard to a novel orthogonal biocatalytic approach, involving two sequential biotransformations, towards the preparation of chiral Oacetylcyanohydrins. Lipase B from Candida antarctica (CalB) and hydroxynitrile lyase from Arabidopsis thaliana (AtHNL) were employed in a robust continuous telescoped process, involving an in situ HCN generation followed by addition to aldehydes and an in-line stabilization of products (scheme 1). Using the formation of (R)-mandelonitrile as an example, the process was optimized with both immobilized isolated enzyme (celite-AtHNL) and whole-recombinant E. coli BL21-DE3 cells expressing AtHNL as biocatalysts.3 Key process parameters and the further applications will be reported. 1 a) Babich, L.; Hartog, A. F.; Van Hemert, L. J. C.; Rutjes, F. P. J. T.; Wever, R. ChemSusChem 2012, 5, 2348 – 2353. b) Yuryev, R.; Strompen, S.; Liese, A. Beilstein J. Org. Chem. 2011, 7, 1449–1467. c) Itabaiana, I.; Leal, I. C. R.; Miranda, L. S. M.; Souza, R. O. M. a. J. Flow Chem. 2013, 3, 122–126. 2 a) Jones, E.; McClean, K.; Housden, S.; Gasparini, G.; Archer, I. Chem. Eng. Res. Des. 2012, 90, 726 – 731. b) Le Joubioux, F.; Bridiau, N.; Sanekli, M.; Graber, M.; Maugard, T. J. Mol. Catal. B: Enzym. 2014, 109, 143 – 153. d) Baxendale, I. R.; Ernst, M.; ...