UvA-DARE (Digital Academic Repository) Enantioselective oxygen-transfer reactions catalyzed by peroxidases Tuynman, A. Publication date 1999 Link to publication Citation for published version (APA): Tuynman, A. (1999). Enantioselective oxygen-transfer reactions catalyzed by peroxidases. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:29 Sep 2021 Introduction Chapter 1 Introduction IOP In order to maintain and to improve the competitive position of the Dutch industries in the world-wide economic scene, the Netherlands Ministry of Economic Affairs promotes innovative research in a number of promising fields. The ultimate goal being "the creation of new economic activity" it has set itself the objective of "providing an essential step on the road from fundamental science to novel applicable technology" [ 1J. Therefore it provides universities and non-profit research institutes with additional subsidiary funding for research projects adapted to the swiftly changing needs of the Dutch industry. Moreover, these programs, called "Innovation Oriented research Programs" (IOP's), are intended to reinforce the collaboration between universities, research institutes and industries. The "Innovative" character is stressed and must be considered from an economical point of view : to make an effort to transform knowledge (science) into know-how (technology). The "technology 5-curve" (Fig. 1) relates the phase of research (in lOP-terms often called "Green Axis") to the applicability or maturity of a technology ("Yellow Axis"). Exploratory Research Applied i DevekjjWflCn't"'^ ! Optimisation Research J ^^^ ' Science i Mission J/ ' • Oriented ; Orienicd J Economic 1 i j evaluation ' Green Ans R&D phase —>- Figure 1. The "technology S-curve" relating the phase of research (in IOP-terms often called "Green Axis") to the applicability or maturity of a technology ("Yellow Axis"). Thus at the start of a project mainly fundamental knowledge is acquired (science oriented). At a certain stage a mission can be defined to pursue an applicable technology, and the research becomes "Mission Oriented". It is at this hinge that the IOP commences to play a role. The Chapter 1 _____ definition of such mission oriented research targets may constraint the academic researchers (bottom-up) but, at the other hand, ensures a solid support from the industry (top-down). IOP catalysis 20 % to 30 % of the Gross National Product of the Netherlands is generated by the chemical industry [ 1 ]. Since catalytic conversions are involved in over 80 % of the total chemical production, it may be of no surprise that catalysis is of strategic interest for the Dutch Industry and can be considered as its cornerstone. Also at the science level Dutch universities have a good international reputation in catalysis research and are called "The Dutch School of Catalysis" [2]. The maintenance and development of the knowledge base of catalysis is therefore an imperative and has recently resulted in the institution of a "National Research School of Combination Catalysis". Central Theme Precision in chemical conversions, in order to save energy and raw materials as well as to avoid the formation of undesired by-products and waste, is the central theme of IOP catalysis. Although catalysis is applied on a large scale in petroleum refining and in the production of bulk chemicals, this is far less the case in the production of fine chemicals. Classical procedures are still applied, using undesirable, toxic and corrosive reagents, that often form by-products and involve low selectivity. Therefore the lOP-catalysis wants to introduce novel catalytic routes in the fine chemical industry. History and Biocatalysis The first four years of lOP's started in 1989, the two focal points being : "catalyst preparation" and "heterogeneous and homogeneous catalysis". The second 4 year programme was established in 1994. "'Catalyst preparation" was extended to "catalyst preparation and reactor technology" constituting 20 % of the budget, "heterogeneous and homogeneous catalysis" made up 40 % of the budget and a third new programme: "Biocatalysis" consumed the rest of the tripod's budget. Biocatalysis was started as a new catalytic tool to achieve in particular enantioselective synthesis of building blocks for pharmaceuticals and flavours and fragrances. It is in the light of these targets, that the research proposal of the present thesis was aimed. Introduction Objective The research described in this thesis was part of the research in the IOP clusterproject [3] : "Peroxidases as catalysts in the production of fine chemicals". This clusterproject consisted of five projects, as listed below: A: IKA94002 Peroxidase mediated biotransformations useful in the biocatalytic production of vanillin, carried out by ir.R.ten Have from the Wageningen Agriculture University under supervision of dr J.A.Field and prof.dr.ir.J.A.M.de Bont. B: 1KA94045 Microperoxidases as biocatalysts in regioselective oxygen-transfer reactions with clean oxidants, carried out by ir.M J.M.van Haandel from the Wageningen Agriculture University under supervision of prof.dr.ir.I. M.CM.Rietjens and prof.dr.ir.C.Laane. C: IKA94047 Peroxidases as natural catalysts in the production of (cnantiomerically pure) alcohols and epoxides, carried out by the author of this thesis, under supervision of dr.R.Wever and prof.dr.H.E.Schoemaker. D: IKA94052 Application of vanadium peroxidases as novel biocatalysts, carried out by drs. H.Bien Brink, under supervision of dr.R.Wever and prof.dr.H.E.Schoemaker. E: 1KA94013 Application of redox enzymes in the synthesis of fine chemicals, carried out by ir. F.van de Velde, under supervision of dr.ir. F. van Rant wijk and prof.dr.R.A.Sheldon. The corollary objective of these project was the development of biocatalysts for the production of fine chemicals via (enantioselcctive) oxidation of industrially accessible starting materials. The first two projects were predominantly focusscd on the development of peroxidases as natural catalysts for the synthesis of flavours and fragrances. The last three projects were aimed at the development of biocatalysts for (enantio)selective oxygen-transfer reactions. An approach of a cluster was chosen to be able to bring together researchers of several complementary disciplines that constitute the broad field of biocatalysis. Thus enzymology, biochemistry, organic chemistry, microbiology and molecular biology were brought together. The objective of the third project and this thesis, has been presented at numerous IOP meetings as : "The development of biocatalysts : (modified) haem peroxidases, useful in the production of chiral epoxides and alcohols" or "Enantioselective oxygen-transfer catalysed by peroxidases". Within the group this specific research was aimed to provide insight into the 3 Chapter 1 mechanistic aspects of these reactions to be able to optimise these conversions with respect to yield and e.e. Whereas other participants had a mission oriented on the application side of the field, this particular research was specifically focussed on the fundamental, scientific knowledge basis of the mechanisms involved to provide support for the other projects in the cluster. Target reactions in this project were the enanlioselective sulphoxidation of thioanisole and the enantioselective epoxidation of styrene to be catalysed by a peroxidase using H202 as a clean oxidant (Fig. 2). S\5 <\ so <^\ H?02 ^^/ CH CH3 ^2» ITT •**,^ + f ^T 3 peroxidase 'vs^' \^ ^> peroxidase (/ Figure 2. Chemical representation of the peroxidase-catalysed (enantioselective) sulphoxidation of thioanisole and the (enantioselective) epoxidation of styrene using H202 as a clean oxidant. For the enantioselective sulphoxidation of thioanisole to form the (R)-sulphoxide already a peroxidase system existed, that yielded this enantiomer in 99 % e.e. [4], being the chloroperoxidase from Caldariomyces fumago. Provided that the right conditions were chosen a complete conversion can be obtained with this catalyst. Research with a more application oriented character on this enzyme i.e. medium engineering and immobilisation studies was carried out in the fifth project. This enzyme also catalysed the enantioselective epoxidation of styrene, although the (ff)-styreneoxide formed had an e.e. of only 49 % [5]. It must be noted that at the moment the best catalyst in the styrene epoxidation, is a Mn-salen complex (Jacobsen-catalyst) that provides 88 % yield of styreneoxide (86 % e.e. (/?)-enantiomer) at - 78°C [6]. Ergo, at the moment a catalyst docs not yet exist, that produces styreneoxide with an enantiopurity that is industrially interesting. Therefore in this research