Halogenated Compounds from Marine Algae

Marine algae produce a cocktail of halogenated metabolites with potential commercial value. Structures exhibited by these compounds go from acyclic entities with a linear chain to complex polycyclic molecules. Their medical and pharmaceutical application has been investigated for a few decades, however other properties, such as antifouling, are not to be discarded. Many compounds were discovered in the last years, although the need for new drugs keeps this field open as many algal species are poorly screened. The ecological role of marine algal halogenated metabolites has somehow been overlooked. This new research field will provide valuable and novel insight into the marine ecosystem dynamics as well as a new approach to comprehending biodiversity. Furthermore, understanding interactions between halogenated compound production by algae and the environment, including anthropogenic or global climate changes, is a challenging target for the coming years. Research of halogenated metabolites has been more focused on macroalgae than on phytoplankton. However, phytoplankton could be a very promising material since it is the base of the marine food chain with quick adaptation to environmental changes, which undoubtedly has consequences on secondary metabolism. This paper reviews recent progress on this field and presents trends on the role of marine algae as producers of halogenated compounds

Global Women’s Breakfast (GWB): #UnidaspelaQuímica

Global Women’s Breakfast (GWB): #BoundbyChemistry. Global Women’s Breakfast is an initiative of the International Union of Pure and Applied Chemistry, aiming to give women scientists, from all over the world, the opportunity to know each other, communicating virtually and sharing their experiences. Many countries joined this initiative and Portugal was not an exception, with its participation already at the first Networking Breakfast in 2011, celebrating the year of the centenaries of Marie Curie Nobel Prize in Chemistry, the Portuguese Chemical Society and the Faculdade de Ciências da Universidade de Lisboa as well. The success of these networking breakfasts, involving students, young researchers, and scientists, encouraged its further organization in Portugal, annually since 2019. This article describes the interventions of Portuguese women scientists, coming from Institutions throughout Portugal, in the Global Women’s Breakfast as partners in their mission as scientists, creative and open to international collaborations. Global Women's Breakfast é uma iniciativa criada pela International Union of Pure and Applied Chemistry para dar oportunidade às mulheres cientistas de todo o mundo de se conhecerem, comunicando virtualmente e compartilhando as suas experiências. A adesão dos países foi muito elevada e Portugal não foi exceção, participando já no primeiro Networking Breakfast em 2011, Ano Internacional da Química, no qual se celebraram os centenários do Prémio Nobel da Química a Marie Curie, da Sociedade Portuguesa de Química e da Faculdade de Ciências da Universidade de Lisboa. O sucesso destes pequenos-almoços em rede, que envolvem estudantes, jovens investigadoras e cientistas, encorajou a continuação da participação de Portugal anualmente, desde 2019. Este artigo descreve a intervenção de mulheres cientistas portuguesas, pertencentes a instituições de Norte a Sul do país, no Global Women’s Breakfast, cúmplices na sua missão de cientistas, criativas e abertas à colaboração internacional

Carbohydrates 2018

This book contains original papers and reviews on carbohydrate research in medicine, authored by participants of the 29th International Carbohydrate Symposium, where this topic had a special emphasis. The focus on biological events involving carbohydrates and glycoconjugates has delivered reliable approaches for disease treatment and diagnosis. Research on carbohydrate-based compounds for therapeutic applications is illustrated in various contributions, namely those covering the development of novel agents against Alzheimer’s disease, e.g. the neuroprotective C-glucosylated flavones and the isonucleoside-based cholinesterase inhibitors. New imino sugar glucosidase inhibitors are also disclosed, a class of compounds with potential for diabetes, Gaucher disease or cancer treatment. Also the development of a useful synthetic method towards multivalent glycoclusters of biomedical interest is here highlighted. The relevance of glycomimetics in drug discovery and the progress on carbohydrates in early diagnosis and cancer treatment are reviewed. Noteworthy is the chitosan-based delivery system for drug oral administration, a new biomaterial-based approach to improve bioavailability. Another study on the conformation of Streptococcus capsular polysaccharide backbones by molecular modelling provides useful information for bacterial immunotherapeutic approaches. All original contributions and reviews clearly demonstrate the potential of glycosciences for innovation in medicinal (glyco)chemistry and pharmaceutical research

Carbohydrate Chemistry

International audienc

Carbohydrate Chemistry

International audienc

Selective anchoring of cyclic thionocarbamates on ketohexoses

Une réaction simple de condensation de l'acide thiocyanique avec un cétohexose peut conduire à la formation d une dizaine de 10 oxazolidinethiones (OZTs) ou oxazolinethiones (OXTs) distinctes. La question que nous nous sommes posée a été comment gérer une chimie aussi complexe? Un contrôle attentif des conditions de réaction, associé à des séquences de purification comportant des protections sélectives et diverses fonctionnalisations, peuvent certainement être utiles. Un jeu chimique subtil et stimulant a été développé entre des pré- et post-protections sélectives et des réactions originales de fonctionnalisation. Dans ce travail de thèse, nous avons mis à l étude de nouvelles tactiques de synthèse et de purification pour accéder à des OZTs et des oxazolidinones (OZOs) ancrées sur des charpentes des cétohexoses. Ces travaux ont été mis en application notamment en série D-fructo et dans les séries épimères D-psico et D-tagato dont la chimie ont été peu explorée en comparaison d autres séries monosaccharidiques. Nous avons ainsi mieux maîtrisé les approches chimiques permettant d accéder à ces thionocarbamates saccharidiques et ainsi de valoriser ces molécules dont l intérêt d un point de vue biologique et chimique est important. Dans ces études, nous avons élaboré une bibliothèque de formes tautomères fixes de composés hybrides qui ont été soumis à des essais biologiques. Ainsi, ce groupe de composés a fait l objet de tests antimicrobiens, livrant des résultats très intéressants. Par ailleurs, les meilleurs inhibiteurs de GLUT5 seront utilisés dans le développement de nouveaux outils biochimiques pour une meilleure compréhension des rôles joués par ce transporteur du D-fructose en relation au le diabète de type 2 et de l'obésité.A simple condensation reaction of thiocyanic acid with a ketohexose can provide a library of up to 10 different molecules composed of oxazolidinethiones (OZTs) or oxazolinethiones (OXTs). The question arising is how to manage such a complex chemistry? Careful control of the reaction conditions associated with purification sequences (involving selective protection or functionalization) can certainly help. A subtle and challenging chemical game could be played between selective pre- and post-protections and original functionalizing reactions. In this PhD work, we disclose the development of new chemical and purification tactics to access OZTs and oxazolidinones (OZOs) anchored onto ketohexose scaffolds, namely D-fructo and its epimers D-psico, D-tagato, whose chemistry has been poorly investigated in comparison with other monosaccharidic systems. Furthermore we have improved our understanding about saccharidic thionocarbamates chemistry for a better valorization from both chemical and biological point of view. We have generated a library of fixed tautomeric forms of hybrid compounds to be submitted to biological tests. This panel of compounds was subjected to antimicrobial screening and some molecules have shown very efficient effects. Moreover, the leading inhibitors of GLUT5 will be used in the development of biochemical tools for a better comprehension of the role of this D-fructose transporter in relation to type 2 diabetes and obesity.ORLEANS-SCD-Bib. electronique (452349901) / SudocSudocFranceF

Synthèse de gem-difluoro-carbasucres

PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFrancePortugalFRP

Synthèse et évaluation biologique de nouveaux dérivés glucidiques contenant un système carbonylé a,b-insaturé dans leur structure

Ce travail de doctorat porte sur la synthèse et utilisation de bicyclolactones glycidiques, de façon à accéder des dérivés de sucres contenant un système carbonylé a,b-insaturé. Trois types de bicyclolactones ont été étudiés: butenolides liés à des cycles furanose, butenolides fusionnés à des cycles pyranose, comprenant S- et NH-analogues et carboxyméthyle glycosides lactones (CMGLs). La méthodologie de synthèse de butenolides sur motif sucre est basée sur l oléfination de Wittig de 3 ou 5-cétosucres et lactonisation intramoléculaire spontanée de gamma-hydroxyesters a,b-insaturés intermédiaires. Pour la synthèse des systèmes fusionnés, des furano-3-uloses protégés ont été convertis en 3-C-(éthoxycarbonyl)méthylène furanoses. Une hydrolyse acide finale permet la transestérification intramoléculaire et aussi l isomérization du cycle en forme pyranose. Des précurseurs 5-S et 5-aminofuranosidiques ont conduit à des analogues thiosucres ou à des dérivés glycidiques ayant une fonction amide et un système carbonylé a,b-insaturé, respectivement. Les CMGLs ont été converties en 3-enopyranosid-2-uloses par l ouverture de la lactone avec une amine et oxydation/élimination du 2-hydroxy pyranoside tri-O-acétylé obtenu. L oléfination de Wittig subséquente a conduit aux diènes conjugués pyranosidiques ramifiés en C-2. Les glycosides contenant un groupement propargyle ont permis de préparer des 1,2,3-triazoles par click chemistry. Quelques molécules ont été soumises à évaluation antimicrobienne et les énulosides de (N-dodécylcarbamoyl)méthyle ont montré les meilleures activités. Le composé le plus actif est l énuloside-a qui a montré un très fort effet contre des espèces de Bacillus et une forte activité contre Enterococcus faecalis et Penicillium aurantiogriseum. Les diènepyranosides ont révélé une activité forte et sélective contre E. faecalis. Les dérivés triazolés n'ont montré aucune activité. Parmi les composés bioactifs, trois sont avérés peu toxiques chez les cellules eucaryotes.This PhD work was focused on the synthesis and the uses of carbohydrate bicyclic lactones for the access to sugar derivatives comprising an alpha, beta-unsaturated carbonyl function. Three types of bicyclic lactones were investigated: furanose C-C-Iinked butenolides, pyranose-fused butenolides, including S-or NH-analogues and carboxymethyl glycoside lactones (CMGLs). The synthetic methodology for butenolide containing-sugars was based on the Wittig olefination of 3- or 5-keto sugars and spontaneous intramolecular lactonization of the intermediate gamma-hydroxy axy alpha,beta-unsaturated esters. In the case of the fused systems, protected furanos-3-uloses were converted into 3-C-(ethoxycarbonyl)methylene furanoses. Further acid hydrolysis elicited both intramolecular transesterification and isomerization to the pyranose ring. Introduction of a sulfur or a nitrogen function at C-5 of the furanose precursors led to thiosugar analogues or to carbohydrate derivatives comprising both an amide function and an alpha,beta-unsaturated system, respectively. CMGLs were converted into 3-enopyranosid-2-uloses by a sequence involving opening of the lactone moiety by amines and oxidation/elimination of the resulting tri-0-acetylated 2-hydroxy pyranosides. Further Wittig olefination afforded 2-C-branched-chain conjugated dienepyranosides. Glycosides bearing a propargyl moiety were engaged in "click" chemistry reactions leading to 1,2,3-triazoles. Some of the new molecules were submitted to antimicrobial evaluation and (N-dodecylcarbamoyl)methyl enulosides proved to display the best efficacy. The most active one was the a-enuloside which showed very strong effect towards Bacillus species and strong activity against Enterococcus faecalis and the fungal pathogen Penicillium aurantiogriseum. Dienepyranosides exhibited a strong activity selectively towards E. faecalis. Triazole derivatives were virtually ineffective. Three of the bioactive compounds showed low acute toxicity in eukaryotic cells.VILLEURBANNE-DOC'INSA LYON (692662301) / SudocVILLEURBANNE-DOC'INSA-Bib. elec. (692669901) / SudocSudocFranceF

Digestibility and Bioavailability of the Active Components of Erica australis L. Aqueous Extracts and Their Therapeutic Potential as Acetylcholinesterase Inhibitors

Erica australis L. (Ericaceae) is used in traditional medicine to treat many free-radical related ailments. In the present work, the stability and biological activity of the plant aqueous extracts submitted to an in vitro digestive process were investigated. Chemical stability was monitored by HPLC-DAD and LC-MS/MS, while the bioactivities were evaluated through the inhibition of acetylcholinesterase (AChE) and DPPH radical scavenging activity. Both extracts, whose main components were flavonol glycosides, inhibited AChE, showing IC50 values of 257.9 ± 6.2 µg/mL and 296.8 ± 8.8 µg/mL for the decoction and for the infusion, respectively. Significant radical scavenging activities were also revealed by both extracts, as denoted by the IC50 values for the decoction, 6.7 ± 0.1 µg/mL, and for the infusion, 10.5 ± 0.3 µg/mL. After submission to gastric and pancreatic juices, no remarkable alterations in the composition or in the bioactivities were observed, suggesting that the extracts may pass through the gastrointestinal tract, keeping their composition and therefore their biological properties. Moreover, the bioavailability of the components of both extracts, as studied in a Caco-2 cell model, showed that compounds can permeate the membrane, which is a condition to exert their biological activities. Our results add further support to the potential of E. australis for its antioxidant and neuroprotective properties