Optimisation of chemoenzymatic processes in asymmetric synthesis

This thesis describes the optimisation of chemoenzymatic methods in asymmetric synthesis. Modern synthetic organic chemistry has experienced an enormous growth in biocatalytic methodologies; enzymatic transformations and whole cell bioconversions have become generally accepted synthetic tools for asymmetric synthesis. Biocatalysts are exceptional catalysts, combining broad substrate scope with high regio-, enantio- and chemoselectivities enabling the resolution of organic substrates with superb efficiency and selectivity. In this study three biocatalytic applications in enantioselective synthesis were explored and perhaps the most significant outcome of this work is the excellent enantioselectivity achieved through optimisation of reaction conditions improving the synthetic utility of the biotransformations. In the first chapter a summary of literature discussing the stereochemical control of baker’s yeast (Saccharomyces Cerevisae) mediated reduction of ketones by the introduction of sulfur moieties is presented, and sets the work of Chapter 2 in context. The focus of the second chapter was the synthesis and biocatalytic resolution of (±)-trans-2-benzenesulfonyl-3-n-butylcyclopentanone. For the first time the practical limitations of this resolution have been addressed providing synthetically useful quantities of enantiopure synthons for application in the total synthesis of both enantiomers of 4-methyloctanoic acid, the aggregation pheromone of the rhinoceros beetles of the genus Oryctes. The unique aspect of this enantioselective synthesis was the overall regio- and enantioselective introduction of the methyl group to the octanoic acid chain. This work is part of an ongoing research programme in our group focussed on baker’s yeast mediated kinetic resolution of 2-keto sulfones. The third chapter describes hydrolase-catalysed kinetic resolutions leading to a series of 3-aryl alkanoic acids. Hydrolysis of the ethyl esters with a series of hydrolases was undertaken to identify biocatalysts that yield the corresponding acids in highly enantioenriched form. Contrary to literature reports where a complete disappearance of efficiency and, accordingly enantioselection, was described upon kinetic resolution of sterically demanding 3-arylalkanoic acids, the highest reported enantiopurities of these acids was achieved (up to >98% ee) in this study through optimisation of reaction conditions. Steric and electronic effects on the efficiency and enantioselectivity of the biocatalytic transformation were also explored. Furthermore, a novel approach to determine the absolute stereochemistry of the enantiopure 3-aryl alkanoic acids was investigated through combination of co-crystallisation and X-ray diffraction linked with chiral HPLC analysis. The fourth chapter was focused on the development of a biocatalytic protocol for the asymmetric Henry reaction. Efficient kinetic resolution in hydrolase-mediated transesterification of cis- and trans- β-nitrocyclohexanol derivatives was achieved. Combination of a base-catalysed intramolecular Henry reaction coupled with the hydrolase-mediated kinetic resolution with the view to selective acetylation of a single stereoisomer was investigated. While dynamic kinetic resolution in the intramolecular Henry was not achieved, significant progress in each of the individual elements was made and significantly the feasibility of this process has been demonstrated. The final chapter contains the full experimental details, including spectroscopic and analytical data of all compounds synthesised in this project, while details of chiral HPLC analysis are included in the appendix. The data for the crystal structures are contained in the attached CD.

Development of small and medium-sized enterprise horizontal innovation networks: UK agri-food sector study

Within the management literature, there is an emergent discourse on horizontal collaboration among small and medium-sized enterprises (SMEs), whereby individual rivalries are overcome by the need for more resources and innovation, leading to increased competitiveness through joint product development. In particular, a number of these horizontal collaborations between SMEs have occurred within the agri-food sector. As a consequence, this article aims to explore the longitudinal development of horizontal innovation networks within an artisan bakers’ network as part of the UK SME agri-food sector. An interpretivist research approach was used, whereby the development and evolution of an artisan bakers’ horizontal network was studied over a 27-month period. The findings, as summarised in conceptual models which draw upon knowledge-based open innovation and social network constructs, illustrate that a complex three-stage life cycle development occurred within the bakers’ horizontal network.

Developing Food Products For Consumers on a Gluten Free Diet

There is a significant increase in people that choose to follow an avoidance diet, especially excluding gluten. Unlike previously, there is now a demand for ‘no compromise’ gluten-free cereal products that have the same properties as their wheat contain counterparts. This is very challenging for the bakers and the cereal technologists due to the functional role of the gluten network in some of these products. Numerous combinations of raw materials form natural sources have been studied and critically evaluated in this review. Most of the gluten-free products are made of native and modified starches blended with different hydrocolloids due to their structure-building and water binding properties. These ingredients are added to a gluten-free flour, such as rice and corn. The legislation framework, formulations for manufacturing of highl nutritional value bread, pasta and cakes/biscuits as well as quality assurance aspects for the gluten-free manufacturers are discussed in this review.

Evaluation of the in vitro biological activities of extracts from carob tree and mediterranean oaks

Dissertação mest., Engenharia Biológica, Universidade do Algarve, 2009

Asma ocupacional en peluquería: una revisión de la literatura

Este artículo pretende realizar una revisión de la literatura vigente acerca del asma ocupacional secundaria a la exposición de los factores de riesgo identificados en peluquería. Se realizó una búsqueda sistemática en las bases de datos PubMed y Cochrane de artículos de revistas indexadas con las palabras claves “Asthma occupational, hairdressers, hairdresser, work related asthma”. Aplicando los criterios de selección descritos, se revisaron 26 artículos en total donde se incluían reportes de casos, estudios de prevalencia, incidencia, corte transversa y revisiones, abarcando principalmente los temas de epidemiologia, fisiopatología, diagnóstico y prevención. Se agruparon según la metodología PRISMA para su respectiva comparación. Se concluyó que a pesar de la importancia de esta patología en el sector de peluquería, existen factores asociados como la informalidad del sector, la falta de estudios de investigación originales de cohorte o el desconocimiento de un protocolo claro de diagnóstico en este tipo de trabajadores, que limitan datos concluyentes acerca de la misma. Sin embargo, la mayoría de los autores concluye la relación entre la patología y la labor de peluquería, así falte esclarecer los mecanismos fisiopatológicos relacionados con los alérgenos identificados.

Biotransformation of alpha-Bromoacetophenones by the Marine Fungus Aspergillus sydowii

The biotransformation reactions of alpha-bromoacetophenone (1), p-bromo-alpha-bromoacetophenone (2), and p-nitro-alpha-bromoacetophenone (3) by whole cells of the marine fungus Aspergillus sydowii Ce19 have been investigated. Fungal cells that had been grown in artificial sea water medium containing a high concentration of chloride ions (1.20 M) catalysed the biotransformation of 1 to 2-bromo-1-phenylethanol 4 (56%), together with the alpha-chlorohydrin 7 (9%), 1-phenylethan-1,2-diol 9 (26%), acetophenone 10 (4%) and phenylethanol 11 (5%) identified by GC-MS analysis. In addition, it was observed that the enzymatic reaction was accompanied by the spontaneous debromination of 1 to yield alpha-chloroacetophenone 5 (9%) and alpha-hydroxyacetophenone 6 (18%) identified by GC-FID analysis. When 2 and 3 were employed as substrates, various biotransformation products were detected but the formation of halohydrins was not observed. It is concluded that marine fungus A. sydowii Ce19 presents potential for the biotransformations of bromoacetophenone derivatives.

Effects of Purified Saccharomyces cerevisiae (1→3)-β-Glucan on Venous Ulcer Healing

Water-insoluble glucan was isolated from the baker’s yeast Saccharomyces cerevisiae. The yeast cells were treated with alkali and the residue then with acid. Chemical and NMR (1D and 2D) analyses showed that a linear (1→3)-β-glucan was purified that was not contaminated with other carbohydrates, proteins or phenolic compounds. The effects of the glucan on wound healing were assessed in human venous ulcers by histopathological analysis after 30 days of topical treatment. (1→3)-β-glucan enhanced ulcer healing and increased epithelial hyperplasia, as well as increased inflammatory cells, angiogenesis and fibroblast proliferation. In one patient who had an ulcer that would not heal for over 15 years, glucan treatment caused a 67.8% decrease in the area of the ulcer. This is the first study to investigate the effects of (1→3)-β-glucan on venous ulcer healing in humans; our findings suggest that this glucan is a potential natural biological response modifier in wound healing

Effects of Purified Saccharomyces cerevisiae (1→3)-β-Glucan on Venous Ulcer Healing

Water-insoluble glucan was isolated from the baker’s yeast Saccharomyces cerevisiae. The yeast cells were treated with alkali and the residue then with acid. Chemical and NMR (1D and 2D) analyses showed that a linear (1→3)-β-glucan was purified that was not contaminated with other carbohydrates, proteins or phenolic compounds. The effects of the glucan on wound healing were assessed in human venous ulcers by histopathological analysis after 30 days of topical treatment. (1→3)-β-glucan enhanced ulcer healing and increased epithelial hyperplasia, as well as increased inflammatory cells, angiogenesis and fibroblast proliferation. In one patient who had an ulcer that would not heal for over 15 years, glucan treatment caused a 67.8% decrease in the area of the ulcer. This is the first study to investigate the effects of (1→3)-β-glucan on venous ulcer healing in humans; our findings suggest that this glucan is a potential natural biological response modifier in wound healing

Neodymium biosorption from acidic solutions in batch system

Biosorption of neodymium in batch experiments took similar to 2 h to achieve the equilibrium biosorbent-metal for all microorganisms tested. The best biosorption coefficient at a constant pH value of 1.5 was obtained using the microalgae Monoraphidium sp. (1521 mg g(-1) cell), followed by Bakers' yeast (313 mg g(-1) cell), Penicillium sp. (178 mg g(-1) cell), and activated carbon (61 mg g(-1) cell). When compared to the biosorption of other metals, these results pointed out to the application of biosorption in neodymium recovery from acidic solutions. (C) 2000 Elsevier B.V. Ltd. All rights reserved.

Use of different carbon sources in cultivation of baker's yeast for production of glycerol-3-phosphate dehydrogenase

The physiological state of yeast cells changes during culture growth as a consequence of environmental changes (nutrient limitations, pH and metabolic products). Cultures that grow exponentially are heterogeneous cell populations made up of cells regulated by different metabolic and/or genetic control systems. The strain of baker's yeast selected by plating commercial compressed yeast was used for the production of glycerol-3- phosphate dehydrogenase. Glycerol-3-phosphate dehydrogenase (GPD) has been widely used in the enzyme assays with diverse compounds of industrial interest, such as glycerol or glycerol phosphate, as well as a number of important bioanalytical applications. Each cell state determines the level of key enzymes (genetic control), fluxes through metabolic pathways (metabolic control), cell morphology and size. The present study was carried out to determine the effects of environmental conditions and carbon source on GPD production from baker's yeast. Glucose, glycerol, galactose and ethanol were used as carbon sources. Glycerol and ethanol assimilations required agitation, which was dependent on the medium volume in the fermentation flask for the greatest accumulation of intracellular GPD. Enzyme synthesis was also affected by the initial pH of the medium and inoculum size. The fermentation time required for a high level of enzyme formation decreased with the inoculum size. The greatest amount of enzyme (0.45 U/ml) was obtained with an initial pH of 4.5 in the medium containing ethanol or glycerol. The final pH was maintained in YP-ethanol, but in the YP-glycerol the final pH increased to 6.9 during growth.

Glicerol quinase de levedura de panificação

Pós-graduação em Alimentos e Nutrição - FCFAR

Utilização de fermento de descarte de cervejaria na produção de aguardente de Licor de laranja

Pós-graduação em Alimentos e Nutrição - FCFAR

Dosagem de etanol utilizando alcool desidrogenase de levedura de panificação

Pós-graduação em Alimentos e Nutrição - FCFAR

Determinação de parâmetros cinéticos de fermentação alcoólica em diferentes substratos

Pós-graduação em Agronomia (Energia na Agricultura) - FCA

Dimensões fractais para certos sistemas dinâmicos discretos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)