Dissertationen zum Thema „Furanic acid“

Doutoramento em Química
The conversion of plant biomass-derived carbohydrates (preferably non-edible) into added-value products is envisaged to be at the core of the future biorefineries. Carbohydrates are the most abundant natural organic polymers on Earth. This work deals with the chemical valorisation of plant biomass, focusing on the acid-catalysed conversion of carbohydrates (mono and polysaccharides) to furanic aldehydes, namely 2-furaldehyde (Fur) and 5-hydroxymethyl-2-furaldehyde (Hmf), which are valuable platform chemicals that have the potential to replace a variety of oil derived chemicals and materials. The investigated reaction systems can be divided into two types depending on the solvent used to dissolve the carbohydrates in the reaction medium: water or ionic liquid-based systems. The reaction temperatures were greater than 150 ºC when the solvent was water, and lower than 150 º C in the cases of the ionic liquid-based catalytic systems. As alternatives to liquid acids (typically used in the industrial production of Fur), solid acid catalysts were investigated in these reaction systems. Aiming at the identification of (soluble and insoluble) reaction products, complementary characterisation techniques were used namely, FT-IR spectroscopy, liquid and solid state NMR spectroscopy, TGA, DSC and GC´GC-ToFMS analyses. Complex mixtures of soluble reaction products were obtained and different types of side reactions may occur. The requirements to be put on the catalysts for these reaction systems partly depend on the type of carbohydrates to be converted and the reaction conditions used. The thermal stability is important due to the fact that formation of humins and catalyst coking phenomena are characteristically inherent to these types of reactions systems leading to the need to regenerate the catalyst which can be effectively accomplished by calcination. Special attention was given to fully inorganic nanoporous solid acids, amorphous or crystalline, and consisting of nano to micro-size particles. The investigated catalysts were silicoaluminophosphates, aluminosilicates and zirconium-tungsten mixed oxides which are versatile catalysts in that their physicochemical properties can be fine-tuned to improve the catalytic performances in the conversion of different substrates (e.g. introduction of mesoporosity and modification of the acid properties). The catalytic systems consisting of aluminosilicates as solid acids and water as solvent seem to be more effective in converting pentoses and related polysaccharides into Fur, than hexoses and related polysaccharides into Hmf. The investigated solid acids exhibited fairly good hydrothermal stabilities. On the other hand, ionic liquid-based catalytic systems can allow reaching simultaneously high Fur and Hmf yields, particularly when Hmf is obtained from D-fructose and related polysaccharides; however, catalyst deactivation occurs and the catalytic reactions take place in homogeneous phase. As pointed out in a review of the state of the art on this topic, the development of truly heterogeneous ionic liquid-based catalytic systems for producing Fur and Hmf in high yields remains a challenge.
Os carboidratos constituem os polímeros naturais mais abundantes na Terra, e a sua valorização química é de grande interesse no contexto das biorefinarias. O objetivo deste trabalho centrou-se na conversão de carboidratos (monossacarídeos e polissacarídeos) em 2-furaldeído (Fur) e 5-hidroximetil-2-furaldeído (Hmf) na presença de catalisadores ácidos, em reatores descontínuos. Fur e Hmf são considerados compostos “plataforma” porque podem ser convertidos numa grande variedade de produtos químicos e materiais (alternativos aos derivados do petróleo). Testaram-se catalisadores ácidos heterogéneos como alternativa aos ácidos minerais que são comumente usados como catalisadores homogéneos para a produção industrial do Fur. Por outro lado utilizou-se água ou um líquido iónico como solvente para a dissolução dos carboidratos no meio reacional. As temperaturas reacionais foram superiores a 150 ºC quando o solvente era a água, e inferiores a 150 ºC no caso de líquidos iónicos. Com o intuito de identificar os produtos reacionais (solúveis e insolúveis), utilizaram-se diferentes técnicas nomeadamente espetroscopia de infravermelho, espetroscopia de RMN de estado líquido e sólido, TGA, DSC e GCxGC-ToFMS. Obtiveram-se misturas complexas de produtos reacionais e discutiram-se aspetos mecanísticos. A estabilidade térmica do catalisador é importante uma vez que a formação de matéria carbonácea insolúvel é característica destes sistemas reacionais tornando-se necessário proceder à regeneração do catalisador por calcinação. Os catalisadores testados foram ácidos inorgânicos nanoporosos, cristalinos ou amorfos, com tamanho de partícula nano ou micrométrico, especificamente silicoaluminofosfatos, aluminossilicatos e óxidos mistos de zircónio e tungsténio. Estes tipos de materiais são versáteis uma vez que as suas propriedades físicoquímicas podem ser modificadas no sentido de melhorar os seus desempenhos catalíticos na conversão de diferentes tipos de substratos (ex. através da criação de mesoporos nos materiais e/ou modificação das propriedades ácidas). Os materiais testados exibiram melhores desempenhos catalíticos para a conversão de pentoses em Fur do que para a de hexoses em Hmf, quando o solvente era a água. Em suma, os catalisadores apresentaram boa estabilidade hidrotérmica. No caso dos sistemas reacionais à base de líquidos iónicos foram verificados elevados rendimentos em Fur e Hmf. especialmente quando os substratos eram a D-frutose ou polissacarídeos relacionados. Contudo, os catalisadores sofreram desativação tal que as reações catalíticas ocorreram em fase homogénea. Conforme explicado numa revisão bibliográfica sobre o estado da arte da conversão catalítica de carboidratos em Fur e Hmf usando líquidos iónicos, o desenvolvimento de sistemas catalíticos heterogéneos à base de líquidos iónicos representa um grande desafio.

Le latex d'Hevea brasiliensis qui contient de grosses quantités de poly(cis-1,4-isoprene) plus communément appelé caoutchouc naturel, est une matière première essentielle pour la production de nombreux produits nécessitant de l'élasticité et provenant de sources naturelles. Le latex se compose de divers autres composants, dont des lipides (~1,3 % en poids du latex frais), avec des variations selon les génotypes. Dans certains génotypes, des lipides contenant une structure furanique peuvent être présents. Ces acides gras furaniques (FuFA) possèdent des propriétés telles que des effets antioxydants, anti-inflammatoires, avec une activité bénéfique sur la prévention des maladies cardiaques, l’amélioration de la masse musculaire, ou encore la prévention des désordres métaboliques. Ces propriétés sont importantes pour améliorer la qualité de vie, ce qui indique un potentiel de découverte de nouveaux produits de haute valeur à partir du latex d'Hevea brasiliensis. Dans cette thèse, 52 génotypes de caoutchouc ont été examinés dans des essais de clones à petite échelle au Cambodge pour évaluer la varialbilité génétique de la concentration de FuFA dans le latex. Les génotypes dont la parenté incluait le clone PB5/51 ont montré un plus haut potentiel de production de FuFA. La quantité de FuFA trouvée était positivement corrélée avec la teneur en acide gras C16:1. La plus forte concentration de FuFA dans le latex frais a été trouvée dans le génotype IRCA 323 (0.71% p/p latex) tandis que la plus grosse production par saignée provient du génotype PB235 (2446 mg/arbre/saignée). Par ailleurs, dans un autre essai agronomique en station experimentale en Thailande, l'influence de trois facteurs agronomiques sur le métabolisme de biosynthese du polyisoprene du latex (évalué par le “diagnostic latex”) et sur la production de FuFA a été étudiée : Saison (échantillons mensuels sur deux années agronomiques) , Systèmes de saignée (S/2 d2, S/3 2d3, et S/2 d3 avec stimulation) et Génotypes (PB235, RRIM600, et RRIT251). Comme prévu, le génotype a été le principal facteur influençant la production de FuFA, le PB235 fournissant de loin la plus grande quantité de FuFA. Le système de saignée n'a eu qu’un effet limité sur le métabolisme du latex et la production de FuFA. La principale variation saisonnière a été une augmentation du rendement en latex tout au long de l'année agronomique, accompagnée d'une hausse du rendement en FuFA. Aucune corrélation n’a été observée entre le métabolisme de la régénération du polyisoprene du latex et la quantité de FuFA. Des stratégies d'extraction et de purification du FuFA ont été étudiées en utilisant le latex PB235 stabilisé à l'ammoniaque. Il a été trouvé que l'extraction utilisant l'acétate d'éthyle avait un potentiel comparable à celui du chloroforme-méthanol pour extraire le FuFA. L'utilisation d’une silice 60A comme phase stationnaire semble être la plus efficace pour séparer chromatographiquement sur colonne les FuFA sous forme de triglycérides (TG-FuFA) des autres lipides présents dans le latex. De plus, la possibilité d’utiliser des enzymes lipolytiques, telles que GPLRP2 et cutinase, pour hydrolyser les lipides contenant du FuFA et potentiellement récupérer le FuFA sous forme d'acides gras libres à partir du latex stabilisé a été démontrée. L'analyse structurelle des TG-FuFA par des techniques de RMN a confirmé la structure du FuFA-F2 (9M5). L'analyse thermique des TG-FuFA par analyse thermogravimétrique sous azote a montré des changements de poids à 420 °C, tandis qu’en présence d'oxygène, des changements de poids se sont produits entre 200-360 °C et 370-530 °C. Ces résultats de recherche indiquent la possibilité de développer des génotypes d’hevea avec une teneur plus élevée en FuFA, confirment l'utilisation de solvants naturels pour l'extraction du FuFA, et présentent des voies de purification du FuFA à l'aide de techniques chromatographiques ou par une approche enzymatique
Hevea latex that contains high amount of poly(cis-1,4-isoprene), commonly know as natural rubber, is an essential raw material for producing many products that require elasticity and come from natural sources. The latex consists of various other components, including lipid (~1.3% by weight of fresh latex), with variations depending on the genotypes. In some genotypes, lipids containing a furan structure can be found. These furan fatty acids (FuFA) possess properties such as antioxidation and anti-inflammatory effects, with beneficial activity in preventing heart diseases, improving muscle mass, and preventing metabolic disorders. These properties are important for improving the quality of life, highlighting the potential of Hevea latex for implementing new high-value by-products. In this thesis, 52 rubber genotypes from a small-scale clone trials in Cambodia were studied to assess the genetic variability of the concentration of FuFA in latex. Genotypes related to the PB5/51 rubber strain were found to have the potential to produce FuFA, and the amount of FuFA found was positively correlated with the C16:1 fatty acid content. The highest FuFA concentration in fresh latex was found in IRCA323 clone (0.71 % w/w latex) and the highest production per tapping was from PB235 genotype (2446 mg/tree/tapping). Moreover, in another experimental trial in Thailand, the influence 3 agronomical factors on the latex cell rubber metabolism (assessed by “Latex diagnosis”), and FuFA production was studied: season (monthly samplings on 2 agronomical years), tapping systems (S/2 d2, S/3 2d3, S/2 d3 with stimulation) and genotype (PB235, RRIM600, and RRIT251). As expected, genotype was the main factor influencing FuFA production, with PB235 yielding a high quantity of FuFA. The tapping system had minimal effect on latex cell rubber metabolism and FuFA production. The primary seasonal variation was an increase in latex yield throughout the agronomical year, accompanied by a rise in FuFA yield. No correlation was observed between latex cell rubber metabolism and FuFA content. Extraction and purification strategies for FuFA were investigated using PB235 latex stablized with ammonia. It was found that extraction using ethyl acetate had comparable potential to chloroform-methanol in extracting FuFA. Using silica 60A as the stationary phase appears to be the most effective method for column chromatography to separate FuFA in the form of triglycerides (TG-FuFA) from other lipids found in latex. Moreover, the use of lipolytic enzymes such as GPLRP2 and cutinase for hydrolyzing FuFA-containing lipids and potentially recover FuFA as free fatty acids from stabilized latex was demonstrated. The structural analysis of TG-FuFA using NMR techniques confirmed the FuFA-F2 (9M5) structure. Thermal analysis of TG-FuFA using TGA under nitrogen conditions showed weight changes at 420°C, while under air conditions, weight changes occurred between 200-360°C and 370-530°C. The research findings indicate the possibility of developing rubber genotypes with higher FuFA content, identifying natural solvents suitable for FuFA extraction, and presenting the feasibility of FuFA purification through chromatography or enzymatic techniques

This thesis describes the use of silver nitrate and iodine to promote 5-endo-dig cyclisations in the synthesis of furans. The oxidation of furylethanols will be discussed as will methods to synthesise furylacetic acids. The total synthesis of a natural product, Plakorsin B will be described along with the total synthesis of the furan fatty acids F5 and F6 as well as giving an overview of their proposed role in Nature. Finally, a new methodology for methylation of halogenated heterocycles will be discussed.

Dietary fish oil supplementation has long been shown to have significant health benefits, largely stemming from the anti-inflammatory activity of the ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) present in fish oils. The anti-inflammatory properties of these fatty acids has been linked to beneficial health effects, such as protecting the heart, in individuals consuming diets rich in fish, or supplemented with fish oils. These effects are highly notable in the Māori people native to coastal regions of New Zealand; the significantly lower rates of heart problems compared to the inland populous has been attributed to the consumption of the green lipped mussel Perna Canaliculus. Commercially available health supplements based on the New Zealand green lipped mussel include a freeze-dried powder and a lipid extract (Lyprinol®), the latter of which has shown anti-inflammatory properties comparable to classical non-steroidal anti-inflammatory drugs (NSAIDs) such as Naproxen. GCMS analysis of Lyprinol by Murphy et al. showed the presence of a class of ω-4 and ω-6 PUFAs bearing a highly electron rich tri- or tetra-alkyl furan ring, which were designated furan fatty acids (F-acids). Due to their instability, isolation of F-acids from natural sources cannot be carried out and a general synthetic route toward this class of natural products was required. To accomplish this, the biosynthesis of F-acids was mimicked by utilising an oxidation of 1,3-dienes, followed by a dehydration/aromatisation to generate the heterocyclic furan ring. Singlet oxygen was chosen as the means of oxidising the conjugated dienes giving endoperoxides. To mimic the biological aromatisation of the peroxide intermediates the Appel reagent was chosen and, in a novel application of the reagent, was exploited as a mild, metal free method of dehydrating the cyclic peroxides to their corresponding furans. The biomimetic furan synthesis was applied toward a selection of 1,3-diene substrates bearing a range of pre-installed functionalities and substitution patterns including alkyl, aryl, alkenes, cyclopropyl rings, silyl ethers, and esters, alongside being applied to the total synthesis of the furan fatty acid F5. A brief exploration of the possibility of performing the aromatisation reaction under catalytic conditions was carried out, to determine whether endoperoxides could be converted to furans without needing a stoichiometric quantity of Appel reagent, by harnessing a catalytic quantity of triphenylphosphine oxide and regenerating the active P(V) species via reaction with oxalyl chloride. Furthermore, an optimisation study was carried out using a simple design of experiments procedure to ascertain the ideal conditions for carrying out the Appel-type dehydration of endoperoxides. Finally, the scope of the reaction sequence was expanded to be performed in a continuous flow reactor, with telescoping of the singlet oxygen diene oxidation and Appel-type aromatisation to increase oxidation yields and to omit the requirement for isolation of peroxide intermediates, and was applied to the synthesis of a selection of 2,5-diaryl furan motifs.

The subject of this thesis is the synthesis and oxidation of tricyclic steroid analogues. The synthesis of the tricyclic derivatives, 1,2-dihydro-5-hydroxy-3H-benz[e]inden-3-ones, is described in chapter 1. The synthetic route involves the initial condensation of readily available acetophenone precursors with furfuraldehyde. Subsequent acidic hydrolysis of the resulting furanyl compounds afforded a diketo acid and/or furan acid depending on the nature and position of the substituent on the aromatic ring. Intramolecular condensation of the diketo acids provides a versatile intermediate in the cyclopentene acetic acid derivatives, the hydrogenation and alkylation of which is discussed in chapter 2. Cyclisation of the acetic acid derivatives with acetic anhydride and subsequent deacetylation provided the tricyclic phenolic compounds. The introduction of angular methyl groups in the cyclopentene acetic acid derivatives is discussed in chapter 2. Reductive methylation of these compounds using lithium in liquid ammonia failed, therefore, hydrogenation, followed by direct alkylation was investigated. Hydrogenation of the esters of the cyclopentene acetic acids gave a mixture of the desired reduced compounds along with the super hydrogenated cyclopentane derivatives. It has been shown that hydrogenation of such systems gives rise to two products, namely the trans cyclopentanone and the cis cyclopentane, the trans cyclopentanone arising through 1,4 addition. Permethylation of these cyclopentanones was achieved using KH, NaH and tBuOK. Chapter 3 deals with the oxidation of the phenols prepared in chapter 1 and the trimethyl compounds prepared in chapter 2. A short review on the oxidation of phenols forms the introduction. The oxidation of the tricyclic compound, 1,2-dihydro-5-hydroxy-3H-benz[e]inden-3-one, using a variety of different oxidising agents did not lead to quinone formation, however phenolic coupling was observed to give a biphenol. Oxidation of the permethylated compounds prepared in chapter 2 with DDQ gave the expected dehydrogenation products via a quinone methide intermediate.

Furan and its derivatives are commonly found in numerous compounds such as natural products, polymers and medicines. The furan ring system is not only the core component to many natural products, but also serves as a key synthetic intermediate to access other more complex molecules. Among furan derivatives, furan fatty acids (F-acids) are an important class of natural products which are widely distributed in nature, and occupy a unique place in the field of medicinal chemistry because of their potent biological and pharmacological activity. This thesis examines the development of novel approaches towards highly substituted furans, with the ultimate goal of applying novel and high efficiency methods to the synthesis of F-acids and their derivatives. The first total synthesis of a natural product, an F-acids metabolite originally isolated from shark (Lamna ditropis) bile, was accomplished by the utilisation of an iodocyclisation of the corresponding 3-alkyne-1,2-diol to construct the furan nucleus; the synthetic route will be discussed in this thesis. Through the study of palladium-catalysis of a formal cyclisation to construct the furan ring system, a general route to access different F-acids has been developed. Splitting the F-acids into relatively simple fragments allows for easy preparation and modification of two fragments to produce a range of F-acids. The synthetic route was then applied to the formal synthesis of a natural product, F-acid F6. After optimisation of the synthetic route, total synthesis of F-acids F4, F6 and their analogues was accomplished.

Ces travaux de thèse portent sur la conversion par catalyse hétérogène du furfural (produit biosourcé produit, par déshydratation du xylose issu de l'hydrolyse acide de l'hémicellulose) en acide 2,5-furane dicarboxylique (FDCA, substituant potentiel de l'acide téréphtalique, monomère de polyesters et polyamides, issu du pétrole). Cette transformation a été envisagée en deux étapes catalytiques: 1) l'hydroxyméthylation du furfural en 5-hydroxyméthylfurfural (HMF) par le formaldéhyde aqueux ou le trioxane en présence d'un catalyseur acide. Les rendements maxima de 40% ont été obtenus en utilisant le formaldéhyde aqueux en présence de nanoparticules de ZSM-5. L'instabilité du furfural et du HMF dans ces conditions réactionnelles est la principale difficulté. 2) l'oxydation aérobie du HMF en FDCA. En milieu alcalin faible (Na2CO3), en présence d'un catalyseur Pt/C promu par le Bi (rapport molaire Bi/Pt = 0,2) à 100 °C et sous 40 bar d'air, le FDCA est obtenu avec un rendement quantitatif. La modification du Pt par le bismuth permet de limiter la lixiviation du Pt dans le milieu réactionnel et de recycler le catalyseur sans prétraitement préalable et sans perte significative de l'activité, comme démontré ensuite en réacteur continu
This thesis reports a study of heterogeneously catalyzed conversion of furfural (biobased product formed from the acid-catalyzed dehydration of xylose) into 2,5-furane dicarboxylique acid (FDCA, possible replacement monomer for terephtalic acid for the production of polyethylene terephtalate). This transformation has been considered in two catalytic steps: 1) hydroxymethylation of furfural with aqueous formaldehyde or trioxane into 5-hydroxymethylfurfural (HMF) in the presence of solid acids. The maximum yields of 40% have been obtained using aqueous formaldehyde in the presence of nanoparticles of ZSM-5. The main problem was the lack of stability of furfural and HMF in reaction conditions. 2) aerobic oxidation of HMF into FDCA. HMF was oxidized in alkaline aqueous solutions over Pt-based catalysts using dioxygen from air. Promotion of the catalyst with bismuth and the presence of a weak base (Na2CO3) yielded a catalytic system with a remarkable activity and selectivity. HMF was completely and exclusively converted to FDCA within 2,5 h. The catalyst could be recovered by simple filtration and reused several times without significant loss of activity and with no platinum or bismuth leaching

La biomasse fait partie des ressources renouvelables qui peuvent répondre durablement à nos besoins de production de carburants, de produits chimiques et de matériaux. En effet, la biomasse non comestible telle que la lignocellulose a attiré l'attention des chercheurs et des scientifiques au cours des dernières décennies en tant qu'alternative renouvelable. Le furfural et le 5-hydroxyméthylfurfural (HMF), dérivés de la déshydratation des pentoses et des hexoses respectivement, sont produits à plusieurs millions de tonnes par an. Ces derniers composés sont donc des molécules plateformes et représentent un intérêt majeur dans le cadre du développement durable. Ce travail vise à explorer des méthodes nouvelles et vertes pour l'oxydation sélective du furfural et de HMF afin de produire des produits biosourcés à haute valeur ajoutée tels que le 2,5-diformylfurane (DFF), l'acide maléique et l'acide succinique. Tout d'abord, un système alternatif d'oxydation de HMF a été présenté, sans l'utilisation de catalyseurs de métaux nobles, de hautes pressions et évitant la production de déchets toxiques. Dans ce contexte, l'oxydation à l'échelle du gramme de HMF conduit à la formation de DFF. Cette réaction a été catalysée par l'acide 2-iodobenzènesulfonique en présence d'Oxone®. Dans des conditions expérimentales optimisées, la conversion du HMF s'est avérée être de 100%, tandis que le rendement et la sélectivité du DFF étaient vers 90%. Par la suite, nous avons démontré un processus sans catalyseur pour la synthèse à l'échelle du gramme de l'acide maléique à partir de furfural en utilisant des irradiations ultrasonores à hautes fréquences. Une sélectivité de 70% en acide maléique avec 92% de conversion du furfural a été obtenue sans aucun catalyseur dans des conditions douces en utilisant H2O2 comme oxydant. Notre approche alternative permet l'utilisation de la biomasse au lieu du pétrole pour synthétiser l'acide maléique à partir du furfural dans un processus écologique et économe en énergie. Enfin, un nouveau procédé catalytique est développé en utilisant des nanoparticules de magnétite, comme catalyseur métallique bon marché et non noble, et du peroxyde d'hydrogène pour l'oxydation du furfural en acide succinique. La conversion totale du furfural a été obtenue avec 67% de rendement en acide succinique dans des conditions douces
Biomass is one of the renewable and green resources that can sustainably meet our needs for the production of fuels, chemicals and materials. Indeed, nonedible biomass such as lignocellulose has attracted attention of researchers and scientists in the last decades as a renewable alternative. Furfural and 5-hydroxymethylfurfural (HMF), derived from the dehydration of pentoses and hexoses respectively, are produced in multimillion ton-scale annually. The latter compounds are, therefore, platform molecules and represent a major interest in the context of sustainable development. This work aims to explore novel and green methods for the selective oxidation of furfural and HMF to produce high value-added bio-sourced products such as, 2,5-diformylfuran (DFF), maleic acid and succinic acid. First, an alternative system of HMF oxidation was presented, without the use of noble metal catalysts, high pressures and avoiding the production of toxic wastes. In this context, the gram-scale oxidation HMF leads to the formation of DFF. This reaction was catalyzed by 2-iodobenzenesulfonic acid in the presence of Oxone®. Under optimized experimental conditions, the HMF conversion was found to be 100%, while the DFF yield and selectivity were almost 90%. Subsequently, we demonstrated a catalyst-free process for the gram-scale synthesis of maleic acid from furfural using high frequency ultrasound irradiations. A 70% selectivity of maleic acid with 92% of furfural conversion were achieved without any catalyst under mild conditions using H2O2 as oxidant. Our alternative approach enables the use of biomass instead of petroleum to synthesize maleic acid from furfural in an eco-friendly and energy-efficient process. At last, a novel catalytic process is developed using magnetite nanoparticles, as a cheap and non-noble metal catalyst, and hydrogen peroxide for the oxidation of furfural into succinic acid. Total conversion of furfural was achieved with 67% of succinic acid yield under mild conditions

À cause du renforcement des réglementations et de l'évolution de l'opinion publique, les tensioactifs issus de la biomasse sont de plus en plus étudiés. À l'heure actuelle, la diversité structurelle de ces composés reste faible et est bien loin de concurrencer les produits issus des ressources fossiles. Pour enrichir les structures disponibles, nous nous sommes intéressés aux composés furaniques, comme le 2,5-diformylfurane (DFF), synthétisés à partir des sucres. Dans cette optique, nous avons tout d'abord généralisé et optimisé une méthode de synthèse originale du DFF. Ce procédé permet de s'affranchir de l'usage des métaux de transition ou des liquides ioniques. Le système utilisé pour convertir des substrats complexes, comme les amidons, repose sur l'action combinée d'acide borique, de bromure de sodium et d'acide formique dans le diméthylsulfoxyde (DMSO). L'acide borique joue un rôle majeur dans ce système puisqu'il est impliqué dans les étapes de déconstruction de la biomasse, d'isomérisation des unités glucose en fructose et dans la formation du HMF. Le bromure de sodium dans le DMSO permet l'oxydation sélective en DFF alors que l'acide formique accélère cette étape. Dans ces conditions, nous avons été capables de produire du DFF à une échelle de plusieurs dizaines de grammes avec des rendements de l'ordre de 20 %. Après l'optimisation de la synthèse, nous avons également étudié le mécanisme d'oxydation impliqué dans cette transformation. La seconde partie de l'étude a été la transformation du DFF en composés tensioactifs. Au terme d'une synthèse de cinq étapes, nous avons obtenu des produits zwitterioniques originaux avec des rendements d'environ 50 %. Ces composés de type gemini issus de la transformation des sucres montrent de bonnes propriétés comme des concentrations micellaires critiques très faibles comparables aux autres tensioactifs gemini déjà étudiés
Due to stricter reglementations and the development of public opinion, surfactants synthesized from biomass are becoming increasingly interesting. However, the structural diversity of these compounds is still too low to compete with the products synthesized from fossil resources. In order to increase the diversity of available structures, we focused on common furanic building blocks, such as 2,5-diformylfuran (DFF), which are synthesized form carbohydrates. Firstly, we optimized a new and innovative synthesis of DFF. This method allowed us to use neither transition metal catalysts nor ionic liquids. The system we used to convert complex substrates, such as starch, relies on boric acid, sodium bromide and formic acid in dimethylsulfoxide (DMSO). Boric acid plays a key role in this system. It is involved in the biomass deconstruction, glucose to fructose isomerization and HMF formation. Sodium bromide in DMSO promotes the oxidation to DFF and formic acid increases the rate of this step. By using this system, we were able to synthesized DFF from glucose at multigram scale with 20% yield. After optimization of the synthesis, we investigated the oxidation mechanism. The second part of this work was focused on the conversion of DFF into new gemini surfactants. At the end of a five steps transformation, zwitterionic products were obtained with 50% yield. These gemini type compounds shows interesting properties such as very low critical micellar concentration which are similar to these measured for already reported gemini surfactants

Methodology studies for cyclic boronate ester synthesis Figure i: Target molecules (see Abstract in pdf for image) Structures i,ii,iii represent a general depiction of cyclic boron-containing heterocyles targeted in this methodology study. These molecules will be made using a range of new organic pathways. A 1,3 nitrogen-boron relationship in selected structures will also be investigated due to its importance in pharmaceutical chemistry. In the pursuit of cyclic boranes a new method for the preparation of unsaturated ketones has been discovered, which utilises the boron chemistry outlined below. Figure ii: Reagents and Conditions: (a) tBuLi, B(OIPr)3, Et2O, -79 °C, 20 % (see Abstract in pdf for image) Novel aspects of furan chemistry It was found that the furan derivative vii, when treated with palladium salts, gave the bis-annulated benzene structure viii. This sequence gave rise to a novel method for the construction of aromatic rings. This reaction was tested on a range of substituted furans in order to examine the scope of this reaction. Figure iii: Reagents and Conditions: (a) Pd(OAc)2, K2CO3, MeCN, 80 °C, 25% (see Abstract in pdf for image).

When food is heated, a vast number of compounds are formed. Some of these are known to be toxic. Among these are furan, HMF, PhIP, IQ, and MeIQx, the subjects of this thesis. All these compounds are known or suspected carcinogens but the detailed mechanisms behind their carcinogenicity have not yet been fully examined. The aim of this thesis was to study genotoxic properties of these compounds using both in vitro and in vivo methods. Clastogenic effects of all five compounds were assessed with the flow cytometer-based micronucleus assay in vivo and for furan also with the micronucleus assay in vitro. DNA-damaging effects of HMF were studied using the comet assay. No induction of micronuclei was obtained after exposure to IQ, MeIQx or furan. Hence, it can be argued that non-genotoxic mechanisms are partly responsible for the carcinogenic properties of these compounds. PhIP, on the other hand, generated a clear response in the in vivo test. Comparing these result with previous results on acrylamide indicates that PhIP is much more potent. However, acrylamide probably poses a higher risk for humans as the intake is considerably higher. For HMF no effects were seen using the in vivo setup. To further investigate the influence of bioactivation of HMF by sulfotransferases (SULTs) the comet assay was performed in cell lines expressing different levels of SULT. However, no correlation between SULT-expression and DNA-damage was observed. Thus, the DNA-damaging effects found in our experimental setup is probably due to other factors than SULT mediated effects. Furthermore, in this thesis the effects of folic acid on chromosomal stability in healthy people were studied. A negative correlation was found between micronucleus frequency and folate status. The results gained within this thesis will hopefully contribute to the risk assessment of compounds present in our diet.

Lignocellulosic biomass has attracted considerable attention as an alternative feedstock for the production of fuels, energy and chemicals, due to its renewability, abundance and reduced cost. Pretreatment and hydrolysation of lignocellulose releases sugars that are subsequently converted by fermentation. However, by-products such as aliphatic acids and furans could be generated during the upstream processes, which could inhibit enzymes and fermenting microorganisms. In addition, fermentation of low-concentrated sugars would lead to low products concentration and, consequently, to higher recovery and purification costs. Therefore, it is beneficial to reduce the concentration of the inhibitors and to concentrate the fermentable sugars in the liquor, prior to the fermentation process. This study was focused on the identification of the operating conditions to effectively remove aliphatic acids and furans from birch pretreatment liquor by nanofiltration. Two commercial NF membranes (NF90 and TS40) were employed. Effects of main operating parameters such as pH, feed concentration, temperature, pressure and tangential velocity on the separation performances were investigated, in both dead-end and cross-flow modes. The membrane performances were compared in terms of retention of sugars and inhibitors, permeate flux and permeability loss. It was found that NF90 membrane was more suitable than TS40 for simultaneous sugars concentration and beneficial removal of the inhibitors. Better separation performances were achieved at pH 1.5, 8 bar, room temperature and 3000 rpm. Dilution of 5 times of the liquor promoted the rejection of the sugars and kept low the retention of the inhibitory compounds. Water permeability loss was recovered by flushing with NaOH and water. The protocol and the operating conditions proposed in this study are suitable to perform the filtration process not only on laboratory scale, but also on industrial scale.

Il paradosso eschimese ha avuto il merito di focalizzare l’interesse dei ricercatori verso la componente lipidica del pescato. È difatti opinione diffusa nonché scientificamente approvata che una dieta a base di pesce è in grado di influenzare positivamente lo stato di salute dell’uomo. Una stretta relazione lega il consumo di pesce ad una bassa incidenza di patologie dell’apparato cardiovascolare, ad una efficace azione neuro protettiva, ma anche ad azioni protettive nei confronti di importanti malattie infiammatorie quali artriti reumatoidi e malattie infiammatorie croniche dell’apparato digerente. I primi studi attribuivano queste attività benefiche esclusivamente alle presenza dei acidi grassi polinsaturi della serie 3, quali l’acido eicosapentaenoico (C20:5), docosapentaenoico (C22:5) e docosaesaenoico (C22:6); recenti studi hanno vagliato la possibilità che anche altri componenti presenti nella frazione lipidica dei pesci siano direttamente coinvolti nella protezione di malattie. Tra questi, particolare attenzione è stata rivolta verso gli acidi grassi furanici (F-Acidi) e i componenti fosfolipidi contenenti acidi grassi 3. Importanti studi sperimentali hanno attribuito agli F-Acidi importanti azioni benefiche nell’organismo umano: attività protettiva nei confronti di patologie coronariche, attività inibitoria dell’aggregazione piastrinica e dell’ureasi batterica, azione antiossidante nei confronti dell’acido linolenico, potenziale attività antitumorale. I fosfolipidi costituiscono le membrane cellulari di tutti gli organismi viventi, sono coinvolti nel processo di invio dei segnali e sono precursori di molecole biologicamente importanti. Inoltre, i loro prodotti di degradazione e ossidazione sono determinanti nelle infezioni dei tessuti e sono coinvolti nelle disfunzioni patologiche come l’ischemia e le infiammazioni. In particolare, le innumerevoli ricerche riguardanti le proprietà biologiche dei fosfolipidi costituiti da acidi grassi 3, unite all’aumento dell’applicazione di tali lipidi nell’industria farmaceutica ed alimentare hanno stimolato lo sviluppo di tecniche analitiche atte a caratterizzare la componente lipidica delle diverse matrici alimentari. Sull’onda di tali considerazioni il presente lavoro di tesi ha avuto come obiettivo la messa a punto di metodiche analitiche innovative in grado di caratterizzare la frazione lipidica di diverse specie ittiche ponendo particolare attenzione all’individuazione e quantificazione dei principali componenti bioattivi (PUFA 3, F-Acidi, specie molecolari fosfolipidiche) . Il lavoro è stato articolato in diverse fasi sperimentali. Nella prima fase sono state individuate e ottimizzate le metodiche analitiche più idonee per la caratterizzazione della frazione lipidica di alcune specie ittiche (pesci, molluschi e crostacei) del mare Adriatico. In dettaglio, l’identificazione e quantificazione dei PUFA 3, degli acidi grassi furanici e delle specie molecolari fosfolipidiche nei diversi prodotti ittici è stata effettuata mediante l’utilizzo di cromatografia liquida e gassosa accoppiate alla spettrometria di massa (GC/FID, GC/MS, HPLC/ESI/MS-MS). Nella seconda fase è stata studiata la distribuzione dei PUFA 3 e degli acidi grassi furanici nelle diverse parti anatomiche dei pesci in relazione al loro ciclo riproduttivo. A tale proposito sono state prese in considerazione due specie di fondamentale importanza per la pesca locale: l’alice e la sarda. Queste due specie presentano un ciclo riproduttivo inverso e sono annoverate fra quelle appartenenti al cosiddetto “pesce azzurro”, una tipologia di pesce considerato povero dal punto di vista del valore commerciale ma valido dal punto di vista nutrizionale perché presenta una frazione lipidica è estremamente ricca di PUFA 3. E’ stata esaminata la frazione lipidica del filetto (parte edibile), del cervello, degli occhi e delle gonadi (normalmente considerati materiale di scarto) delle due specie ittiche campionate nell’arco di un anno. Nella terza parte sperimentale sono state caratterizzate le specie molecolari fosfolipidiche di due tipologie di pescato: pesci ossei e molluschi. Tra i pesci ossei sono state prese in esame anche due specie alloctone, scelte tra le più diffuse a causa del loro basso prezzo di acquisto, e una specie di acqua dolce nostrana. I valori ottenuti dalle analisi dei profili lipidici del pangasio, del persico e della trota fario confrontati con quelli ottenuti dalle altre specie marine in esame hanno prodotto interessanti risultati dal punto di vista della qualità, mettendo in evidenza somiglianze e differenze tra le componenti lipidiche delle specie indagate. Nella quarta parte l’attenzione è stata rivolta verso tre specie di crostacei. La frazione lipidica delle parti edibili di mazzancolle, pannocchie e granchi è stata analizzata con particolare attenzione verso la caratterizzazione delle specie molecolari fosfolipidiche. In questo studio sono state separate alcune tra le principali frazioni lipidiche, mediante estrazione in fase solida. Dopo aver purificato lipidi neutri, fosfatidilcolina, fosfatidiletanolammina e il suo plasmalogeno l’attenzione è stata focalizzata sulla presenza degl’acidi grassi furanici e quindi sulla loro distribuzione nelle differenti frazioni lipidiche purificate. In conclusione il lavoro si propone di affinare tecniche analitiche già esistenti nonché di metterne a punto nuove. Oltre ad analizzare quantitativamente le specie ittiche prese in considerazione, la caratterizzazione della frazione lipidica ha consentito l’individuazione di bio marker, ovvero molecole caratteristiche presenti esclusivamente in alcune specie piuttosto che in altre. Nell’ottica della lotta contro un sempre crescente numero di frodi legate alla genuinità dei prodotti ittici lavorati, tali indicatori potrebbero rivelarsi un interessante strumento per attività di controllo analitico.
The Eskimo paradox had the virtue of focusing the interest of researchers towards the fish lipid fraction. Diet rich in fish products is considered able to influence positively human health, and this is approved widely by scientific community. A relationship linking the consumption of fish product with a low incidence of cardiovascular diseases, high neuroprotective activity, protective action against inflammatory diseases such as rheumatoid arthritis and chronic inflammatory diseases of the digestive system. In early studies, these activities were exclusively attributed to the presence of 3 polyunsaturated fatty acids (PUFA 3), such as eicosapentaenoic acid (C20:5), docosapentaenoic (C22:5) and docosahexaenoic acid (C22:6). Recent studies supposed the possibility that also other components of fish lipid fraction were directly involved in the protection of cardiovascular disease. Among these components particular interest was focused on furan fatty acids (F-Acids) and phospholipids containing PUFA 3. Experimental studies about F-Acids behavior were able to carry out significant activities such as: protection against coronary heart disease, inhibition of platelet aggregation and bacterial urease, antioxidant activity in order to preserve the linolenic acid and potential antitumor activity. Phospholipids make up cell membranes of all living organisms, they are involved in the process of sending signals and they are precursors of biologically important molecules. Moreover, their degradation and oxidation products are crucial role in tissue infections and dysfunction in many pathological conditions such as ischemia and inflammation. The numerous studies on the biological properties of phospholipids rich of PUFA 3 and an increasing applications of these lipids in the pharmaceutical and food industries have stimulated the development of analytical techniques in order to characterize the phospholipids fraction of foods. The aim of the work was the development of innovative analytical methods able to characterize the lipid fraction of some important fish species in the Adriatic Sea in order to identify and quantify the bioactive compounds (i.e. PUFA 3, F-Acids and phospholipids molecular species). The study was divided in different experimental sections. In the first experimental section, analytical methods for the fish lipid fraction characterization were developed in order to result the most appropriate ones. In detail, the identification and quantification of PUFA 3, F-Acids and phospholipids molecular species of various fish products were investigated using gas and liquid chromatography coupled with mass spectrometry (GC/FID, GC/MS, HPLC/ESI/MS-MS). In the second section, the distribution of PUFA 3 and F-Acids in different anatomical parts of fish and their relationship with reproductive cycle were studied. Two important species of pelagic fish were analyzed: anchovy and sardine. They represent a considerable product for local fisheries markets and they are characterized by reversed reproductive cycle. Moreover they can be considered as a cheap fish source but their nutritional value is very high, because their lipid fraction is extremely rich in PUFA 3. The lipid fraction of fillets (edible part), brains, eyes and gonads (usually considerate as waste) were investigated for both species. The sampling was carried during one year. In the third experimental phospholipid molecular species of two types of seafood were characterized: bony fish and molluscs. Among the bony fish also two allochthonous species were investigated, these are spread in italian markets because of their low price. The database obtained from the analysis of lipid profiles of pangasius, perch and brown trout compared with those obtained from other marine species produced interesting results in terms of quality, in order to underline similarities and differences between the lipid components of the species investigated. Three crustaceans were investigated in the fourth experimental. The phospholipid molecular species of the edible parts of mantis shrimp, caramote prawn and crab were characterized. In order to study the distribution of furan fatty acids in the different lipid fractions, the neutral lipids, phosphatidylcholine, phosphatidylethanolamine and its plasmalogens were separated using solid phase extraction tool and their fatty acid profiles were defined. In conclusion, the work had the aim to refine existing analytical techniques and to put up new ones. Moreover the characterization of the lipid fraction allowed the identification of biological markers. These markers can be considered an excellent tool able to investigate not only as regards qualitative parameters but also quantitative. The markers system could be a valid help for fish food control activities. In fact markers have already been utilized for quality control of many food products. In order to combat a growing activities of fraud related to the authenticity of processed fish products. Finally these quality indicators represent an interesting tool for food analytical quality control.

Ce travail décrit de nouvelles voies de synthèse d'hétérocycles phosphoniques. La première partie concerne l'étude de la formation d'indoles phosphoniques via un intermédiaire benzénique, convenablement substitué en vue d'une hétérocyclisation. Deux voies de synthèse ont retenu notre attention nous permettant de préparer des 3-phosphonoindoles porteurs d'une fonction amine, alkyle, aryle ou hydroxyle. La première voie fait appel à une réaction de couplage entre l'orthoiodonitrobenzène et un phosphonate α-fonctionnel, puis une hydrogénation du groupement nitro suivie de la réaction de cyclisation. La deuxième fait intervenir une réaction de métallation-fonctionnalisation en α du phosphore d'un benzylphosphonate porteur en ortho d'une fonction amine protégée ; la deuxième étape est une réaction de déprotection et de cyclisation. La deuxième partie de ce mémoire décrit la synthèse de furanes et de pyrroles phosphoniques via une réaction de Paal-Knoor. Les intermédiaires-clés, porteurs de deux sites électrophiles, ont été synthétisés à partir de phosphonocétal ou acétal par métallation-fonctionnalisation. Enfin nous avons synthétisé une pyridazine phosphonique par réaction entre un phosphonate β,γ'-dicarbonylé et l'hydrazine, puis oxydation de l'intermédiaire. La synthèse des intermédiaires phosphonates β,γ'-dicarbonylés nous a permis d'étudier une réaction de réarrangement du type phosphonate-phosphoramide conduisant, suivant les conditions, soit à un composé α,delta-dicarbonylé non phosphoré, soit a un pyrrole N-phosphorylé.

Une nouvelle méthode pour la préparation de gamma-butyrolactones optiquement pures est proposée. Une stratégie de synthèse donnant accès à deux types de chirons carbonylés (cétones et aldéhyde) a permis le développement de deux réactions hautement stéréosélectives créant ainsi un troisième centre stéréogénique : la réduction des cétones, (2R, 3R)-2,3-dipivaloxy-4-oxo alcanoates de méthyle par le borohydure de sodium dans le méthanol mène aux alcools correspondants (4R), avec des ee>98%, précurseurs des (2R,3S,4R)-2,3-dipivaloxy-4-alkylbutyrolactones. L'addition d'organomagnésiens sur l'aldéhyde (2R,3R)-4-oxo-2,3-dipivaloxy butanoate de méthyle conduit de façon spontanée aux (2R,3S,4S)-2,3-dipivaloxy-4-alkylbutyrolactones avec des ee>98%, épimères des précédentes. Les étapes de lactonisation et de déprotection ont donné accès aux (2R,3S,4R) et (2R,3S,4S)-2,3-dihydroxy-4-alkylbutyrolactones optiquement pures. Certaines de ces lactones ont permis les synthèses formelles de quatre produits naturels : (3R, 4R)-quercus lactone, (-)-avénaciolide, (+)dodécanolactone, (+)-tétrahydrocérulénine enfin, une nouvelle synthèse totale de la L-bioptérine, important composé intervenant comme cofacteur d'enzymes dans de nombreuses réactions biologiques, est effectuée à partir de l'acide L-tartrique via le 5-déoxy-l-arabinose issu de la (2R,3S,4S)-2-3-dihydroxy-4-méthylbutyrolactone.

La cycloaddition du dichlorocetene avec des éthers d'enols chiraux conduit à des cyclobutanones fonctionnalisées avec une diastéréosélectivité élevée. Cette réaction est basée sur la différenciation des faces de la double liaison de l'oléfine chirale. Des intermédiaires de pureté enantiomerique élevée, comme les gamma-butyrolactones, sont obtenus à partir des cycloadduits. Au cours de ce travail, nous avons effectué les premières synthèses enantioselectives des produits naturels suivants: la (moins)-methylenolactocine et l'(moins)-acide protolichesterinique. Ces alpha-méthylène-gamma-butyrolactones possèdent des propriétés antibiotiques et antitumorales importantes. Dans cette partie du travail une réaction d'alpha-méthylation de gamma-butyrolactones a été mise au point. Dans un deuxième temps, nous avons effectué la synthèse asymétrique d'un certain nombre de gamma-butyrolactones beta-oxygénées: (moins)-blastmycinolactol, (plus)-blastmycinone, (moins)-nfx-deux et (plus)-antimycinone, composés issus des antibiotiques antimicynones a(trois) et a(un) respectivement

Ketonization is a promising reaction for the upgrading of bio oils produced from biomass and it is used for the preparation of highly valuable asymmetrical ketones such as di-hydrocalchone (HC) and acetyl furan (Ac-Fur). But, they are produced in the liquid-phase with poorly sustainable processes, e.g. Friedel-Crafts acylations (Ac-Fur) and tandem acylation/alkylation (HC) with homogeneous Lewis acid catalysts or oxidations with organic peroxides and excess MnO2 (HC) or H2O2 and inorganic homogeneous catalysts. The development of an alternative gas-phase process to produce HC and Et-Fur by means of cross-ketonization is highly desirable because it would avoid the issues of traditional methods. Moreover, most reactants required for the ketonization process could be prepared from renewable resources. This thesis was dedicated to the study of the cross-ketonization between ethyl benzoate (EB) and ethyl-3-phenylpropionate (EPP) and between ethyl acetate (EtOAc) and ethyl-2-furoate (Et-Fur) to synthetize HC and 2-Ac-Fur respectively. Ketonization of EPP with EB was carried out over different metal oxides (namely ZrO2, La2O3, CeO2) and it was found that ZrO2 was the best catalyst, probably due to its amphoteric properties. Over this material, the formation of HC was maximized by a large excess of EB (EB/EPP= 9) and by a high reaction temperature (350 °C); the effect of water co-feeding was also evaluated in the attempt of maximize HC yield by hydrolyzing EB in situ and producing the more reactive BA, but it was found that instead water reduces catalyst activity. Similar conclusions were drawn investigating the ketonization of Et-Fur with EtOAc over ZrO2. In conclusion, HC was obtained with 80% selectivity at 77% EPP conversion at 350 °C, with 1 second and with a EB/EPP molar ratio = 9, while Ac-Fur was obtained with 82% selectivity at 82% Et-Fur conversion in the same conditions but with a lower EtOAc/Et-Fur molar ratio of 4.

L'étude de la réactivité régio- et stéréosélective du bromure de bromobenzyle nous a permis de synthétiser des motifs styréniques métallés par un bras espaceur de 1 à 3 atomes de carbone ainsi que des motifs bis-aryles en présence de sels de palladuim (catalyse de type Stille ou Suzuki). La synthèse régio- et stéréosélective d'acides et dérivés insaturés β,γ- ou α,β- dihalogénés équivalents à des systèmes tris-électrophiles nous a conduit à étudier la réactivité de ces synthons. L'étude de la réactivité par catalyse palladiées d'acides insaturés β,γ-dihalogénés à conduit à la formation d'acide pyrrol-3-yl acétiques substitués, en une seule étape, selon une quadruple séquence. Ces acides ont permis de former des motifs 5H-furan-2-ones substitués en position 4, par cyclisation intramoléculaire puis couplages palladiés. Une série de différentes catalyses palladiées régio- et stéréosélective sur des acides insaturés α,β-dihalogénés, a permis d'obtenir des oléfines tri-substituées, notamment des précurseurs de dérivés du Naproxène ayant potentiellement des applications pharmaceutiques intéressantes et des motifs 3-alkylidène-4-halogéno-3H-furan-2-ones
The study of the regio- and stereo selective reactivity of the bromobenzyl bromide allowed us to synthesize styrenic compounds metaled with a space arm of 1 or 3 atoms of carbon and bi-arly compounds palladuim salts(Stille or Suzuki cross coupling). The selective synthesis of insaturated acids and esters β,γ ou α,β-dihalogenated equivalents with tris-electrophils systems led us to study the reactivity of these compounds. The study of the reactivity of insaturated acids β,γ-dihalogenated with palladuim cross coupling led to the formation of substituted pyrrol-3-yl acetics acids in one stage according to a triple sequence. These acids also made it possible to form 4-substituted pyrrol-3-yl acetics acids in one stage according to a triple sequence. These acids also made it possible to form 4-substituted-5H-furan-2-ones by intramolecular cyclisation and then cross coupling. A series of different selectivity palladuim cross coupling on insaturated acids α,β-dihalogenated allowed to obtain trisubstituted olefins, in particular precursors of derived from Naproxen having potentially interesting pharmaceuticals applications and 3-alkylidene-4-halogeno-3H-furan-2-ones

Une synthèse sélective des deux monoéthers de l'isosorbide a été réalisée. Ces composés ont été utilisés comme auxiliaires chiraux en réduction asymétrique de cétones prochirales par le borohydrure de sodium. Des aminoéthers et aminoalcools ont été synthétisés et leur comportement a été étudié en alkylation asymétrique d'amides phénylacétiques. Des diastéréosélectivités allant jusqu'à 83% ont été observées

Nouvelle voie d'acces, par synthese organosilicique a partir de propargyltrimethylsilanes omega -fonctionnels, a des vinylidene-3 oxolannes, oxannes, oxepannes, oxocannes, a des vinylidene-5 dioxanne-1,3 et a des heterocycles a deux heteroatomes (o, s, n). Processus d'aminomethylation-desilylation intramoleculaire permettant l'acces direct a des vinylidene-3 pyrrolidines, piperidines et perhydroazepines. Protodesilylation de propargyltrimethylsilanes varies a l'aide du complexe trifluorure de bore-acide acetique, conduisant generalement a des allenes terminaux fonctionnels

Nowadays environmental problems, climate changes, limited fossil resources and their price fluctuation, associated with industrial activity (often ecologically unsound) are the strong driving forces for governments, companies and scientists to find alternatives to the fossil-based materials. In this scenario 2,5- furandicarboxylic acid (FDCA), a renewable platform chemical has emerged as the most promising substitute to terephtalic acid for the synthesis of several materials, particularly polyesters, which possess similar thermal and mechanical proprieties. These materials could be applied to current applications and, could even be applied in new, innovative and high value applications. In this context, the development of sustainable FDCA-based polymers and materials is timely and quite relevant. Precisely, the main objective of this thesis is the development of more sustainable polymers and composites based on FDCA and a wide panoply of aliphatic compounds selected for their renewable origin (PART B) and/or the improved thermal and mechanical properties they can impart the ensuing materials. Furthermore, the potential of a new FDCA-based ester monomer as plasticiser for partial replacement of the non-renewable di(2- ethylhexyl) terephthalate on PVC formulations was also evaluated (PART C). In the first study, a partially renewable polyester based on FDCA and 1,4- cyclohexanediol, namely poly(1,4-cyclohexylene 2,5-furandicarboxylate) (PCdF) was prepared aiming at preparing a new material with enhanced thermal properties. Its synthesis was performed by two distinct approaches, namely via solution polycondensation and bulk polytransesterification. For comparative purposes, poly(1,4-cyclohexanedimethylene 2,5-furandicarboxylate) (PCF) homopolyester was also synthesised, due to their related structural resemblance. Homopolyesters with different molecular weights (Mn and Ð values ranging between 4 300-14 100 g/mol and 1.2-1.7, respectively) were obtained, depending on the synthesis approach and catalyst used. The resulting materials revealed to possess semi-crystalline character with high glass transition temperatures (Tg values of 175 and 105 ºC for PCdF and PCF, respectively), and thermal stablility up to 377 ºC. It was also found that, the absence of the methylene group on PCdF homopolyester, lead to a more rigid polymer chain backbone, and accordingly to a highest Tg. Other studies, focused on the development of copolyesters enterelly based on renewable-based monomers, namely those based on FDCA, 1,4-butanediol and poly(propylene oxide) or diglycolic acid were performed. In a second study, several poly(1,4-butylene 2,5-furandicarboxylate)-copoly( poly(propylene oxide) 2,5-furandicarboxylate) (PBF-co-PPOF) poly(esterether) s copolymers were synthesised using dimethyl 2,5-furandicarboxylate and different molar ratios of 1,4-butanediol and poly(propylene oxide). The ensuing copolyesters presented either semi-crystalline character when using higher PBF feed amounts, or completely amorphous viscous liquid was obtained instead when using a PBF/PPOF ratio equal to 1 . Moreover, these materials presented high thermal stability (maximum degradation temperatures between 340-365 ºC), and low Tgs (values ranging from -42.3 to -32.6 ºC), facilitating their processability at lower temperatures. Further, in a third stud, comprised the preparation of a series of FDCA-based nanocomposites were prepared using poly(1,4-butylene 2,5-furandicarboxylate)- co-poly(1,4-butylene diglycolate) (PBF-co-PBDG) copolyesters and acetylated bacterial cellulose (Ac-BC). In a first step, PBF-co-PBDG (co)polyesters were synthesised; followed, in a second step, by the preparation of nanocomposites films obtained by solvent-casting approach. Interestingly, for higher incorporation of BDG moieties, these reinforced materials showed an increased stiffness (Young’s modulus up to 1239 MPa) and reasonable elasticity (elongation at break values between 0.6 to 25.0 %) compared to their neat (co)polyester counterparts. Furthermore, similar values of oxygen permeability of nanocomposites and (co)polyesters were observed, expanding the exploitation of these materials for packaging applications. Finnaly, a fourth study, addressed the possibility of using a furanic ester as an additive for poly(vinyl chloride) (PVC). A combination of di(2-ethylhexyl) 2,5- furandicarboxylate (DEHF) and di(2-ethylhexyl) terephthalate (DEHT) plasticisers was performed into an attempt to increase the ‘green content’ of PVC formulations. These materials have shown to possess higher compatibility with the PVC matrix compared with DEHF as single plasticizer, confirmed by FTIR spectroscopy. Furthermore, they displayed thermal features comparable to those prepared with DEHT as single plasticizer (Tg’s between 19.2 to 23.8 ºC), and increased elongation at break (up to 330%). Moreover, migration tests revealed very low weight loss percentages, not exceeding ca. 0.3 and 0.2%, for water and PBS solution, respectively. More important, preliminary results of in vitro cell viability tests (concentrations up to 500 μM for a maximum of 72 h) revealed a non-toxic profile (around 100 %) for both DEHF and DEHT plasticisers. All FDCA-based materials and chemicals prepared under the scope of this dissertation are an important contribute for the increasing demand for new renewable-based products, within a sustainable approach. Further, these materials and chemicals, presented similar or improved properties to those prepared from petroleum-based resources.
Nos dias de hoje, os problemas ambientais, as mudanças climáticas, os recursos fósseis limitados e sua flutuação de preço, associados à atividade industrial (muitas vezes muito pouco ecológicas) são as forças motrizes para governos, empresas e cientistas encontrarem alternativas para os materiais preparados a partir de recursos fosséis. Neste cenário, o ácido 2,5- furandicarboxílico (FDCA), em produto químico de origem renovável, surgiu como o substituto mais promissor do ácido tereftálico na síntese de diversos materiais, particularmente poliésteres, que possuem propriedades térmicas e mecânicas semelhantes. Estes materiais podem ser utilizados nas aplicações existentes, e em outras novas aplicações, inovadoras e de alto valor. Neste contexto, o desenvolvimento de polímeros e materiais sustentáveis a partir dos furanos é oportuno e bastante relevante. Precisamente, esta tese tem como principal objetivo o desenvolvimento polímeros e materiais compósitos mais sustentáveis a partir do FDCA e uma panóplia de compostos alifáticos selecionados pela sua origem renovável. Posteriormente, foi ainda avaliado o potencial de um novo monómero éster preparado a partir do FDCA como plastificante para a substituição parcial do não renovável tereftalato de di(2- etilhexilo) em formulações de cloreto de polivínilo (PVC). No primeiro estudo, foi preparado um poliéster parcialmente renovável a partir do FDCA e do 1,4-ciclohexanodiol, nomeadamente o poli(2,5- furanodicarboxilato de 1,4-ciclohexileno) (PCdF) com o objectivo de se obter um novo material com propriedades térmicas melhoradas. A sua síntese foi efetuada a partir de duas abordagens distintas, nomeadamente via policondensação em solução e politransesterificação em estado sólido. Por motivos comparativos, foi ainda sintetizado o homopolímero poli(2,5- furandicarboxilato de 1,4-ciclohexanodimetileno) (PCF), devido à semelhança estrutural entre ambos. Homopolímeros com pesos moleculares diferentes foram obtidos de acordo com a abordagem de síntese e catalisadores utilizados (valores de Mn e Ð variando entre 4 300-14 100 g/mol e 1.2-1.7, respetivamente). Os materiais resultantes revelaram possuir carácter semi-cristalino com elevadas temperaturas de transição vítrea (valores de Tg de 175 e 105 ºC, para o PCdF e PCF, respetivamente) e estabilidade térmica até aos 377 ºC. Verificouse ainda que, a ausência do grupo metileno no homopolímero PCdF, deu origem a um material com estrutura de cadeia polimérica mais rígida, e consequentemente um valor de Tg mais elevado. Num segundo estudo, vários copolímeros do poli(2,5-furanodicarboxilato de 1,4- butileno)-co-poli(2,5-furanodicarboxilato de poli(óxido de propileno)) (PBF-co- PPOF) poli(éster-éter)s foram sintetizados a partir do 2,5-furanodicarboxilato de dimetilo e diferentes rácios molares do 1,4-butanodiol e do poli(óxido de propileno. Os copolímeros resultantes apresentaram caráter semi-cristalino quando quantidades superiores de PBF foram usadas, líquidos viscosos completamente amorfos quando o rácio PBF/PPOF usado foi igual a 1. Mais ainda, estes materiais apresentaram elevada estabilidade térmica (temperaturas de degradação máxima entre 340-365 ºC, e baixas Tg´s (valores a variar entre os - 42.3 a -32.6 ºC), facilitando desta forma o seu processamento a mais baixas temperaturas. Adicionalmente, num terceiro estudo, abrangendo a preparação de uma série de nanocompósitos à base de FDCA, preparados usando os copolímeros poli(2,5-furanodicarboxilato de 1,4-butileno)-co-poli(diglicolato de 1,4-butileno) (PBF-co-PBGD e celulose bacteriana acetilada (Ac-BC). Numa primeira etapa, os copolímeros foram sintetizados; seguida da preparação de filmes de nanocompósitos, obtidos através da abordagem de evaporação de solvente. Curiosamente, para uma maior incorporação de unidades de BDG, estes materiais reforçados demonstraram um aumento de rigidez (módulo de Young até 1239 MPa) e elasticidade aceitável (valores alongamento até à ruptura entre 0.6 até 25.0 %) quando comparados com os seus (co)polímeros homólogos puros. Além disso, foram observados valores similares para as permeabilidade ao oxigénio dos nanocompósitos e (co)polímeros, expandindo a exploração destes materiais para aplicações como embalagens. Finalmente, um quarto estudo, abordou a possibilidade de usar um éster furânico como aditivo para formulações de poli(cloreto de vinilo) (PVC) (Capítulo VI). A combinação dos plastificantes 2,5-furanodicarboxilato de di(2-etilhexilo) (DEHF) com o tereftalato de di(2-etilhexilo) (DEHT) foi efetuada de forma a aumentar o ‘conteúdo verde’ das formulações de PVC. Estes materiais demostraram possuir maior compatibilidade com a matriz do PVC comparativamente com os preparados apenas com o DEHF. Mais ainda, apresentaram características térmicas comparáveis aos preparados apenas com o DEHT (Tg’s entre 19.2 e 23.8 ºC) e um aumento do alongamento até à rutura (até 330%). Além disso, os testes de migração revelaram muito baixas percentagens de perda de massa, não excedendo os 0.3% e os 0.2%, respetivamente, para a água e para a solução PBS. Mais importante, resultados preliminares em testes de viabilidade celular in vitro (concentrações até 500 μM e máximo de 72 h) revelaram um perfil não-tóxico para ambos os plastificantes, DEHF e DEHT. Todos os materiais e químicos preparados a partir do FDCA dentro do âmbito desta dissertação são uma importante contribuição para a crescente procura por novos materiais de origem renovável, dentro de uma abordagem sustentável. Mais, estes materiais e químicos apresentaaram propriedades semelhantes ou melhoradas às dos preparados a partir de recursos petrolíferos.
Programa Doutoral em Química Sustentável

碩士
國立臺灣師範大學
化學系
101
This thesis contains two topics. The first part is the synthesis of pyrroles via 1.2 equiv TMSOTf-promoted tandem reaction of 2-(4-arylpropargylamino- methyl)-3,5,5-trimethyl-2,3-epoxy-cyclohexa-1-ones. The reaction underwent a tandem semi-pinacol rearrangement/alkyne-ketone metathesis to obtain pyrroles. While 1.0 equiv BF3•OEt2 is required for the synthesis of the furans from 2-(4-aryl-propargyloxymethyl)-3,5,5-trimethyl-2,3-epoxy-cyclohexa-1- ones. The second part is the synthesis of azaspirocycles via FeBr3-promoted tandem reaction of 3-(4-arylpropargylaminomethyl)-2,3-epoxy-cyclohexa-1- ones. The reaction underwent a tandem semi-pinacol rearrangement/alkyne– aldehyde metathesis.

碩士
國立雲林科技大學
環境與安全衛生工程系
103
The awakening to the fossil fuel limitation and sustainable development forces human to explore renewable and environmental friendly energy. Bioethanol is one potential candidate because it can be produced using pretreated lignocellulosic biomass, the most abundantly available raw material on the EarthIn recent years, algal biomass is considered as the idealraw material to produce renewable energy because of itshigh cellulosecontent and fast growth rate. Moreover, algae are well-known carbon dioxide capturer. Algae can be incubated in freshwater or seawater so thatthe land demand is minor. Taiwan is a small island country but surrounded by abundant algal resources. Using algal biomass for renewable energy production in Taiwan may be an ideal way to approach sustainable future. Thermal acid hydrolysis is extensively used to pretreat algal biomass because of economic and efficient consideration. However, the main drawback of thermal acid hydrolysis is to produce inhibitor compounds such as acetic acid, furfural and 5-hydroxymethyl furfural (5-HMF) during hydrolysis. These inhibitor compounds will influence downstream bioethanol fermentation. For better bioethanol yield, inhibitor compounds removal is an important issue. In 2004, US Department of Energy suggests top 14 biomass platform molecules for the sustainable future.. Among these compounds, 2,5-furan-dicarboxylic acid (FDCA) can be produced by 5-HMFbio-transformation. Basing on the connection between 5-HMF removal in the algal acid hydrolysate and FDCA production, microbes capable of biotransforming 5-HMF into FDCA could be beneficial to high bioethanol yield and potential molecule production. In this study, we collected algaChaetomorpha linumfrom waste fishing field as the raw material for thermal acid hydrolysis.To find out the best hydrolysis condition to obtain high reducing sugar concentration and hydrolysis efficiency, various parameters (acid sorts, algal concentrations, acid concentrationsand hydrolysis time) were investigated. In addition, potential microbes transforming 5-HMF into FDCA were enriched and isolated from an activated sludge tank of food factory and campus soil.Their abilities of 5-HMF biotransformation and FDCA production were investigated under various initial pHs, temperatures and 5-HMF concentrations. The isolates were also used to biotransform 5-HMF into FDCA in the algal acid hydrolysate. Optimum thermal acid hydrolysis condition was to apply0.5 M HCl to treat 3% algae at 121℃ for 15 minutes. The highest reducing sugar concentration and hydrolysis efficiencywere 6.32 g/L and 50%, respectively. There were 14 strains isolated from the activated sludge of soy sauce wastewater treatment system and the campussoil. Among these isolates, strain G-2 and H-2, the most potential two strains, were identified as Methylobacterium radiotolerans and Burkholderia cepacia, respectively, by 16S rDNA sequences.Strain MethylobacteriumradiotoleransG-2 could completely transform 1000 mg/L 5-HMF into FDCA at initial pH of 7 at 26C and maximum FDCA concentration was 513.9 mg/L. Strain Burkholderia cepacia H-2 transformed 2000 mg/L 5-HMF into FDCA at initial pH of 7 at 28C and 1276 mg/L FDCA was received.For 5-HMF biotransformation in the algal acid hydrolysate, 2-fold dilution was suitable for strain MethylobacteriumradiotoleransG-2, and 459.7 mg/L FDCA was obtained. Reducing sugar consumption was less than 16%. Strain Burkholderia cepacia H-2 was suitable to treat the algal hydrolysate without dilution, and 989.5 mg/L FDCA was received, but reducing sugar consumption was high, 43%.

碩士
國立雲林科技大學
環境與安全衛生工程系
107
Lignocellulosic biomass is an ideal resource for biofuel production, but reducing sugar of lignocellulosic biomass used for biofuel production is released only after pretreatment. Dilute acid thermal hydrolysis is one of the extensively applied pretreatment methods. However, the main disadvantage of this pretreatment is that inhibitors such as 5-hydroxymethylfurfural (5-HMF), formic acid and phenol are also formed during hydrolysis. These inhibitors cause a decrease in the yield of biofuel. Therefore, it is necessary to detoxify these inhibitors to improve market competitiveness of bioenergy. Among numerous methods to detoxify inhibitors, biological detoxification is superior to physical and chemical detoxification because of its no extra waste production and mild operating conditions. Strain Burkholderia cepacia H-2 and Cupriavidus metallidurans Y-d are isolated from our previous studies. The strain B. cepacia H-2 is 5-HMF biotransforming bacterium and can convert the inhibitor 5-HMF into high value 2,5-furandicarboxylic acid (FDCA). Strain Cupriavidus metallidurans Y-d is phenol degrading bacterium. Both strains had the potential to detoxify the inhibitors in the lignocellulosic hydrolysate and produce valuable compound simultaneously. In order to explore the feasibility of two strains to be applied for biodetoxification, the aims of this research included to explore (1) the utilization of reducing sugars by two strains, (2) the ability of strain C. metallidurans Y-d to degrade different hydrolysis inhibitors, (3) the effect of 5-HMF conversion in the presence of single and multiple inhibitors, and (4) the biodetoxification by coinoculating two bacteria. The results showed that strain B. cepacia H-2 consumed glucose and xylose, but phenol-degrading bacteria C. metallidurans Y-d could not utilize glucose and xylose. The strain C. metallidurans Y-d could not degrade 5-HMF, furfural and formic acid, and levulinic acid but it could degrade phenol and acetic acid. Acetic acid concentration below 1500 mg/L could be completely detoxified by strain C. metallidurans Y-d. Strain C. metallidurans Y-d could degrade 667 mg/L phenol, and phenol detoxification efficiency was 60%. Formic acid also has a negative effect on 5-HMF conversion. When the formic acid concentration was 1500 mg/L, the 5-HMF conversion rate was 58.3 mg/L/hr. When the formic acid concentration increased to 4500 mg/L, 5-HMF conversion rate droped to 36.0 mg/L/hr. The low concentration of levulinic acid was beneficial for 5-HMF conversion. The 5-HMF conversion rate in the presence of 1500 mg/L levulinic acid was the highest, 102.2 mg/L/hr, and was 1.9 times higher that that in the absence of levulinic acid. However, when levulinic acid concentration further increased, the positive effect was not significant. Acetic acid had no significant effect on 5-HMF biotransformation, but increasing its concentration caused the reduction of 5-HMF conversion rate. 5-HMF utilization efficiency decreased to 68.3% in the presence of 800 mg/L phenol, comparing to the control (in the absence of phenol). The 5-HMF conversion and FDCA production in the presence of multiple inhibitors were analyzed by the statistical software. The inhibitor casuing the most significant negative effect on 5-HMF conversion was phenol, followed by furfural according to the S/N ratio calculation. On the contrary, furfural was the inhibitor casuing the most significant negative effect on the FDCA prodction, followed by phenol. In the presence of multiple inhibitors, the furfural*phenol combination had the greatest negative effect on both 5-HMF conversion and FDCA production, followed by phenol*acetic acid and furfural*acetic acid combinations. Co-culture of strains B. cepacia H-2 and C. metallidurans Y-d could detoxify 1000 mg/L 5-HMF, 1000 mg/L furfural and 4500 mg/L levulinic acid. The highest FDCA production concentration was 1053.2 mg/L.

Papua New Guineans have medicinal knowledge based on thousands of years of using flora, fauna and fungi as medicines. However, factors such as poor documentation and an increase in the use of allopathic medicine within the island have promoted the rapid loss of such medicinal knowledge. Thus the work presented in this thesis has been directed towards the preservation of first hand traditional knowledge, as it pertains to the use of mushrooms by indigenous inhabitants of Papua New Guinea, in particular those mushrooms with medicinal potential. A compilation of biologically active secondary metabolites isolated from terrestrial and marine fungi from Papua New Guinea under ethnomycology is presented in chapter one. A brief account of ethnomycology by early Europeans and inhabitants of the new world in pre-Columbian times is also presented. Chapter two describes the in vitro biological testing of mushrooms used by the Kiovi, Waefo and Kopanka clans. Turbidity-MTT microdilution assay was used to determine the susceptibility of Gram (+) and Gram (-) bacteria against 52 crude mushroom extracts resulting in approximately 31% of the samples tested active against at least one of the organisms used. Ethnomycological comparisons between the Kiovi, Waefo and Kopanka are also presented. The work described in chapter three includes ethnomycological and taxonomical background of Fulaga dive, common name given to a mushroom member of the Amanitaceae family and used by the Kiovi tribe for its edibility and because it makes them “feel well”. Bioassay guided isolation, purification and structural elucidation of two novel furan fatty acids is detailed. Chapter four details the synthetic route of the two novel furan fatty acids isolated from Fulaga dive. The synthesis was achieved from commercially available furan. Degradation of this class of compounds is also discussed, where (Z)-9-(5-pentylfuran-2-yl)-non-8-enoic acid isomerises to the more stable (E)-diastereoisomer followed by olefinic cleavage producing 5-pentyl-2-furaldehyde. Chapter five reports the synthesis of 26 compounds, that are furan based homologues and thiophene based analogues of (Z)-9-(5-pentylfuran-2-yl)-non-8-enoic acid. Homologues and analogues were assayed for their antibacterial potential against a panel of bacterial human pathogens using the turbidity-MTT assay and their radical scavenging properties using the DPPH assay. Finally, chapter six includes ethnomycological and taxonomical background of Igura hivi, a mushroom also used by the Kiovi tribe for its edibility and treat stomach complaints. Bioassay guided isolation, purification and structural elucidation of the known antibiotic grifolin is presented. The spectroscopic data obtained for the isolated fungal metabolite matched that reported in the literature.

碩士
國立東華大學
化學研究所
88
PNAs(Peptide Nucleic Acids),was find out have many bioactive. This organic molecule have much application in medicine,biot- echnology. For development more power modified backbond structure,we fi- nd out substituted furan PNA have good molecular structure p- roperties. This paper is focus on synthesis of substituted furan PNA mo- nomers containing the four natural nucleobases: thymine,cyto- sine,adenine,and guanine by efficient total synthesis.

碩士
國立雲林科技大學
環境與安全衛生工程系
105
Lignocellulose is the most abundant biomass on Earth, and its cellulosic polysaccharide is suitable used as raw material for bioenergy production. To release polysaccharide from lignocellulose and further hydrolyze polysaccharide into simple sugar, pretreatment is necessary and beneficial for subsequent fermentation process. Thermal acid hydrolysis is extensively applied and econamic pretreatment method to deal with lignocellulosic biomasses, but inhibitors are inevitably formed during this process. 5-Hydroxymethylfurfural (5-HMF) is the main inhibitor compound produced, and other inhibitors, such as organic acids, furfural and phenols are also commonly generated during thermal acid hydrolysis. These inhibitors seriously influence downstream bioenergy production. Therefore, inhibitors removal is an important issue. In 2004, the US Department of Energy announced 12 top biomass platform molecules for the sustainable future. 2,5-Furan-dicarboxylic acid (FDCA) is present in this list. FDCA can be obtained by 5-HMF biotransformation, and it can replace terephthalic acid (TA) to produce synthetic green plastic material, polyethylene-2,5- furandicarboxylate (PEF). Compared with suspended cells, immobilized cells have several advantages. The adventages include easy solid-liquid separation, low separation cost, high cell density maintenance and toxic compounds resistance. Based on the connection between 5-HMF detoxification in lignocellulosic hydrolysates and FDCA production, our previous isolate strain Burkholderia cepacia H-2 capable of biotransforming 5-HMF into FDCA was used in this study. In order to evaluate the feasibility of the immobilized Burkholderia cepacia H-2 for 5-HMF biotransformation. First, 5-HMF biotransformation using suspended cells and immobilized cells was compared. Then, the optimal inoculum size and stability of immobilized cells were studied. Finally, the effects of various inhibitors/salinity and thier concentrations on 5-HMF biotransformation were investigated. The results showed that the immobilized cells had better 5-HMF biotransformation and FDCA production efficiencies, and stable 5-HMF conversion at low pH. 1851 mg/L 5-HMF could be completely converted into FDCA within 32 hours. As increasing bacterial concentrations in the immobilized cells, 5-HMF biotransformation time was shortened. The optimal inoculum size in the immobilized cells was 175 mg/L (equal to O.D. 0.3). 1894 mg/L 5-HMF could be entirely biotransformed within 24 hours, and 1917 mg/L FDCA was received at the end of experiment. Immobilized cells with and without dead bacterial cells could adsorb 5-HMF and FDCA. As reuse cycles numbers of the immobilized cells increased, 5-HMF conversion efficiency decreased. 5-HMF conversion efficiency was higher than 75% after 16 reuse cycles. The higher the formic acid concentration, the lower the 5-HMF conversion rate. 5-HMF conversion efficiency was not significantly affected as formic acid concentration was 3000 mg/L, but enhanced as formic acid concentration was lower than 1000 mg/L. When increasing formic acid concentration to 5000 mg/L, FDCA production and 5-HMF conversion efficiencies obviously declined. In addition, strain Burkholderia cepacia H-2 was capable of degrading formic acid. Acetic acid concentration lower than 4390 mg/L did not affect 5-HMF biotransformation and FDCA formation, and 5-HMF conversion efficiency was between 87~90%. High furfural concentration had a negative effect on 5-HMF conversion and FDCA generation rates. When furfural concentration was higher than 1000 mg/L, 2000 mg/L 5-HMF could not be completely converted. Besides, furfural was utilized by immobilized strain Burkholderia cepacia H-2. There was no significant effect of levulinic acid on 5-HMF biotransformation. Furthermore, strain Burkholderia cepacia H-2 could use levulinic acid as carbon source to support biomass growth. The higher the phenol concentration, the lower the 5-HMF conversion rate. However, phenol had no significant effect on 5-HMF conversion efficiency. With the increase of NaCl concentration, 5-HMF conversion and FDCA production rates both obviously decreased. When NaCl concentration was higher than 6%, 5-HMF could not be completely biotransformed, but 5-HMF conversion efficiency was not influenced.