A dissertation submitted to the School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Science. Johannesburg, 2015 / Cyanogenesis is defined as the hydroxynitrile lyase catalysed release of a cyanide group in the form of hydrogen cyanide and the corresponding aldehyde or ketone. When a plant is attacked, the hydrogen cyanide released is a self-defence mechanism. A special characteristic of enzymatic reactions is that all enzymatic reactions are reversible - hydroxynitrile lyases can also be used for the synthesis of enantiomerically pure cyanohydrins which are of great importance in industry. In this study, the hydroxynitrile lyase activity of 102 plants from 41 families was investigated, first by screening for cyanogenic activity, followed by a hydroxynitrile lyase activity assay. Six plants were found to be cyanogenic and exhibited specific hydroxynitrile lyase activity: Adenia sp. (0.44 U/mg), Adenia firingalavensis (2.88 U/mg), Adenia fruticosa (1.99 U/mg), Adenia pechuelii (2.35 U/mg), Heywoodia lucens (1.76 U/mg) and Ximenia caffra (1.84 U/mg). This is the first report of hydroxynitrile lyase activity in these plants.

Thesis (Ph. D.)--University of Oregon, 2008. / Typescript. Includes vita and abstract. Includes bibliographical references (leaves 195-204). Also available online in ProQuest, free to University of Oregon users.

Acrylic monomers are important materials that represent a large portion of the economy. The current industrial synthesis hydrates cyanohydrins with sulfuric acid, a process which results in large amounts of waste and significant energy costs. A transition metal catalyzed, acid free hydration of cyanohydrins would be beneficial from both economic and environmental standpoints. However, this reaction is challenging, as many catalysts are poisoned by the cyanide released when cyanohydrins degrade. Therefore the development of a catalyst that is resistant to cyanide poisoning is the ideal method to circumvent these difficulties. This dissertation describes several cyanohydrin hydration catalysts, with an emphasis on nanoparticle catalysts. These are at the interface between the homogeneous and heterogeneous catalysts that have been explored previously for this reaction. Chapter I surveys previous studies on nanoparticle catalysts for nitrile hydration and their implications for the hydration of cyanohydrins. Chapter II reports on the homogeneous platinum catalysts [PtHCl(P(NMe2)3)2] and [PtH2(P(NMe2)3)2], exploring secondary coordination sphere effects to enhance nitrile hydration. Chapter III describes another example of this type of complex, [PtH2(P(OMe)3)2], that forms catalytically active nanoparticles under reaction conditions. Explorations of the reactivity of this catalyst with nitriles and cyanohydrins are also described in this chapter. Chapter IV investigates a silver nanoparticle catalyst with a water soluble phosphine (1,3,5-triaza-7-phosphaadamantane) ligand for its activity towards the hydration of nitriles and cyanohydrins. The results of the degradation of the nanoparticles in the presence of cyanide are also described. Chapter V reports on the preparation and examination of a solid supported nickel catalyst for cyanohydrin hydration. Finally, Chapter VI describes how these investigations have made progress towards the development of a cyanide resistant nitrile hydration catalyst. This dissertation includes previously published and unpublished co-authored material. / 2015-09-29

xx, 204 p. A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number. / Efforts toward developing improved methods of synthesizing acrylamides are ongoing. Several homogeneous organometallic and coordination complexes have proven useful in catalytic acrylonitrile hydration; however, none of these complexes have been tested in the hydration of cyanohydrins used to synthesize substituted acrylamides. This dissertation describes the reactivity of molybdocene and Pt phosphinito nitrile hydration catalysts toward cyanohydrin substrates and the effect of Cp ring substituents on aqueous molybdocene chemistry. Chapter I identifies the motivation for developing a transition metal-catalyzed process for cyanohydrin hydration and the strategy used to improve on the reactivity of molybdocene catalysts. Chapter II reports the effect of cyclopentadienyl ring substituents on the electronic and geometric structure, solution behavior, and hydrolytic activity of molybdocenes. To examine the effect of Cp ring substituents, ansa -molybdocenes containing the fragment {C 2 Me 4 (C 5 H 4 ) 2 }Mo 2+ were compared to non-bridged molybdocenes containing (C 5 H 5 ) 2 Mo 2+ and (C 5 H 4 Me) 2 Mo 2+ . Addition of a tetramethylethylene-bridge decreases the electron density on the Mo center and exerts a small effect on the structure of the metallocene. However, the catalytic activity of the molybdocene catalysts is unchanged or slowed because of counteractive effects on the bound nucleophile and electrophile. Although adding substituents to the Cp rings did not change the catalytic activity of the molybdocene, the substituents led to significant changes in the equilibrium behavior. The equilibria have practical consequences that warrant investigation. Chapters III and IV chronicle the effect of Cp ring substituents on the monomer-dimer equilibria and the acidity of the molybdocene complexes, respectively. Interestingly, the monomer-dimer equilibrium established by ansa -{C 2 Me 4 (C 5 H 4 ) 2 }Mo(OH)(OH 2 ) + exhibits a strong solvent dependence. New equilibrium schemes are reported for the ansa and non- ansa complexes. Chapter V describes the reactivity of the molybdocene and Pt phosphinito catalysts toward cyanohydrins. Both catalysts gave unsatisfactory results; however, the à à à à à ±-hydroxy substituent of cyanohydrins facilitates nitrile hydration. The low reactivity exhibited by these systems was due to liberation of hydrogen cyanide from the cyanohydrin leading to acute poisoning of either catalyst. As discussed in Chapter VI, this study will expedite the innovation of new catalysts that are better suited to overcome the challenges associated with cyanohydrin hydration. This dissertation includes previously published and unpublished co-authored material. / Adviser: David R. Tyler

This thesis describes the development and rationalization of processes involved in a new methodology developed in our group, minor enantiomer recycling. The first part of the thesis addresses mechanistic studies of one of the reactions involved in minor enantiomer recycling, dual Lewis acid-Lewis base catalyzed acetylcyanation of aldehydes. The methodology uses a combination of a chiral titanium-salen  complex with a tertiary amine as a catalytic  system  in  the enantioselective  synthesis  of  O-acylated  cyanohydrins from aldehydes and ketonitriles. Mechanistic investigations revealed that the rate-determining step in the reaction changes, depending on the nature of the aldehyde that was used. It was also concluded that cyanohydrin is coordinated to the Lewis acid in the acylation step. The second part of the thesis deals with minor enantiomer recycling, a highly selective one-pot recycling system. In a first step the product is formed as a minor and a major enantiomer by asymmetric catalysis. Recycling of the minor enantiomer, by selective kinetic resolution, regenerates the starting material. Continuous addition of a second reagent, also involved in a coupled exergonic process, leads to an increase of both yield and enantiomeric excess. Recycling procedures for the synthesis of O-acylated and O-formylated cyanohydrins have been developed with high yield and high enantiomeric excess of the products. The study includes development of the systems, comparison to other methodologies in asymmetric catalysis, and attempts to understand the processes involved. / <p>QC 20141202</p>

This thesis deals with the development of new methods for efficient synthesis and analysis in asymmetric catalysis. It focuses on the preparation of chiral cyanohydrins by enantioselective addition of cyanide to prochiral aldehydes. The initial part of the thesis describes the development of a dual Lewis acid– Lewis base activation system for efficient synthesis of chiral O-acylated and Ocarbonylated cyanohydrins. This system was used for the preparation of a variety of cyanohydrins in high isolated yields and with up to 96% ee. Activation of the cyanide by nucleophilic attack of the Lewis base at the carbonyl carbon atom was supported experimentally. Secondly, convenient procedures for the synthesis of polymer-bound chiral YbCl3-pybox and Ti-salen complexes are described. The polymeric complexes were employed in cyanation of benzaldehyde. A T-shaped microreactor was used for screening of reaction conditions for the enantioselective cyanation of benzaldehyde using trimethylsilyl cyanide and acetyl cyanide as cyanide sources. A microreactor charged with the polymeric Tisalen complex was used for enantioselective cyanation of benzaldehyde. Finally, an enzymatic method for high throughput analysis of ee and conversion of products from chiral Lewis acid–Lewis base-catalysed additions of α- ketonitriles to prochiral aldehydes was developed. The method could be used for the analysis of a variety of O-acylated cyanohydrins. Microreactor technology was successfully combined with high throughput analysis for efficient catalyst optimisation. / QC 20100809

This thesis deals with method development in asymmetric catalysis and specifically syntheses of enantioenriched O-functionalized cyanohydrins. The first part describes the development of a method for the synthesis of O‑alkoxycarbonylated and O-acylated cyanohydrins. Ethyl cyanoformate and acyl cyanides were added to aldehydes in a reaction catalyzed by a chiral dimeric Ti-salen complex together with a tertiary amine. High yields and enantioselectivities were in most cases obtained. Mechanistic studies were performed and a reaction mechanism was proposed. ­ The second part describes a method in which the undesired minor enantiomer in a Lewis acid–Lewis base-catalyzed acylcyanation is continuously recycled into prochiral starting material. Close to enantiopure O‑acylated cyanohydrins were obtained in high yields. The third part deals with asymmetric acylcyanations of ketones. Acetyl cyanide was found to add to α‑ketoesters in a reaction catalyzed by a chiral Lewis base. Yields up to 77% and 82% ee were obtained. The final part describes an enzymatic method for high-throughput analysis of O‑acylated cyanohydrins. The enantiomeric excess and conversion were determined for products obtained from a number of aromatic and aliphatic aldehydes. / QC 20100818

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

<p>Enzymes are useful tools as specific analytical reagents. Two different analysis methods were developed for use in the separate fields of protein science and organic synthesis. Both methods rely on the substrate specificity of enzymes. Enzyme catalysis and substrate specificity is described and put in context with each of the two developed methods.</p><p>In <strong>paper I </strong>a method for C-terminal peptide sequencing was developed based on conventional Carboxypeptidase Y digestion combined with matrix assisted laser desorption/ionization mass spectrometry. An alternative nucleophile was used to obtain a stable peptide ladder and improve sequence coverage.</p><p>In paper<strong> II </strong>and <strong>III</strong>, three different enzymes were used for rapid analysis of enantiomeric excess and conversion of O-acylated cyanohydrins synthesized by a defined protocol. Horse liver alcohol dehydrogenase,<em> Candida antarctica</em> lipase<strong> </strong>B<strong> </strong>and pig liver esterase were sequentially added to a solution containing the O-acylated cyanohydrin. Each enzyme caused a drop in absorbance from oxidation of NADH to NAD⁺. The conversion and enantiomeric excess of the sample could be calculated from the relative differences in absorbance.</p>

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal