Search

International audience; The development of a highly convenient and efficient protocol for iterative solution-phase synthesis of shorter oligomers of para- and meta-arylopeptoids is described. Peptide coupling methods for accessing longer oligomers were studied: use of the new coupling reagent COMU was found to be the most efficient for creation of the tertiary benzamide bonds. The cis/trans isomerism of arylopeptoid backbones was studied by NMR and was found to be highly dependent on the nature of the side chains. Increasing bulkiness of theside chains favored the cis amide bond conformation; arylopeptoids possessing tert-butyl side chains contained exclusively cis amide bonds

In the course of our search for a new class of HMG-CoA reductase inhibitors, the synthesis of reaction intermediate analogues was investigated. Compound 2, having the C-5 (R) configuration of natural mevinic acids, was prepared in enantiomerically pure form starting from levoglucosan. During this synthesis, an epimerisation of the olefinic intermediate 16 was observed and was found to depend strongly both on the axial or equatorial orientation and on the nature of the C-3 substituent. Biological activity of compound 2 is reported.

The coupling of metalated pyridine derivatives with a chiral Weinreb amide derived from gluconolactone followed by stereoselective reduction of the resulting ketone are the key steps of the synthesis of bisubstrates analogues of the HMGCoA reduction by HMGR.

Partially protected sugar lactones reacts with stabilized phosphoranes at high temperature yielding activated olefins which undergo subsequent 1,4-addition to give bicyclic adducts, simultaneous furan formation being also observed.

Efficient conditions for the synthesis of C -glycosylidene compounds from lactones based on Wittig reactions of cyanomethyl triphenylphosphoranylidene involving microwave heating are described: subsequent stereoselective reduction of the anomeric olefins gave the corresponding C -glycosides in good yields with high stereocontrol.

Dibromoolefination of lactones was achieved in high yields using bromomethylenetriphenylphosphorane in refluxing tetrahydrofuran. This reaction is believed to proceed via bromination of the monobromophosphorane from the corresponding bromomethyltriphenylphosphonium bromide with concomitant formation of methylenetriphenylphosphorane as shown by 31P NMR. Transylidation should occur to afford the reactive dibromomethylenetriphenylphosphorane.

Communication orale

Azide- and alkynyl-containing homo-beta(3)-peptides, of up to six residues in length, were synthesised in solution from aspartic acid. Their subsequent conjugation with monosaccharides bearing an azide or a terminal alkyne function was efficiently achieved by copper-mediated cycloadditions leading to two novel families of small glycoclusters. These compounds represent ideal tools to explore carbohydrate-mediated multivalent interactions.

β-Amino esters prepared from activated exo-glycals are transformed into acyclic C-nucleoside with a C-4-substituted uracil derivative that can be cyclized under Mitsunobu conditions to provide a new family of fused-ring analogues of uridine nucleoside in which the N-1 nitrogen atom is embedded in an imino sugar ring. An analogue of uridine of d-ribo configuration is prepared.

Poster

Poster

Poster

Poster

International audience; The synthesis of a novel family of peptidomimetics composed of linear and cyclic α,β-alternating peptoids is described. Oligomers consisting of up to six peptoid residues (n = 1−3) were synthesized on large scale with use of an efficient iterative solution-phase method and longer oligomers (n = 4, 5) were obtained by the coupling of appropriately protected shorter oligomers. Preliminary conformational studies of these hybrid peptoids are reported.

The synthesis and solution conformation of homo-oligomers of beta-aminoacids, beta-N-mannofuranosyl-3-ulosonic acids, have been studied by NMR, MD simulation, and circular dichroism. These oligomers feature a spirocyclic disubstitution and a N,O-acetal functionality at the beta-carbon of the backbone, an unprecedented situation in the realm of beta-peptides. Our study shows that tetramer 10 and hexamer 11 adopt a characteristic secondary structure. In the hexamer 11, NMR investigations coupled with MD simulations suggest the preference for a double C(8) turn forming conformation.

International audience; beta-Amino esters prepared from activated exo-glycals are transformed into acyclic C-nucleoside with a C-4-substituted uracil derivative that can be cyclized under Mitsututed conditions to provide it new Family of fused-ring analogues of uridine nucleoside in which the N-1 nitrogen atom is embedded in an amino sugar ring. An analogue of uridine of D-1 ibo configuration is prepared.

The first synthesis of functionalized beta-peptoid macrocycles is reported. X-ray crystallographic structure of tetramer 9 reveals a C2-symmetrical derivative with unexpected all-cis-amide bonds and spatial disposition of the appendages toward the two opposite faces of the ring. Quantum calculations suggest that 9 is locked in this layout. These macrocycles constitute novel promising templates for multimeric ligation of biologically active ligands. The concept was exemplified by chemical decoration of tetramer 9 via "click" reactions.

Cycloaddition reactions of activated exo-glycals and nitrones proceeded only under microwave activation, with excellent facial selectivities on furanoglycosylidenes and good stereocontrol on the nitrone producing only two diastereomeric spiroisoxazolidines. α/β-Spiro sugar-isoxazolidines are obtained from pyrano exo-glycals. The cycloaddition reaction with nitrile oxide proceeds at room temperature and gives open-chain isoxazoles due to facile β-elimination of the sugar ring oxygen on the intermediate isoxazoline ring system. All the heterocycles obtained this way can be regarded as nucleoside analogues.

The first structural investigations were undertaken on a β-hexapeptide 7 in which the peptide backbone is constrained by cis -substituted oxetane rings. Detailed NMR studies in CDCl 3 and C 6 D 6 together with molecular mechanics conformational analysis identify a well-defined left-handed helical structure stabilised by 10-membered hydrogen-bonded rings. Comparison with two related hexapeptides 8 and 9 suggests a similar structural preference for these systems.

The crystal structure of the title compound, C24H28O8, has been determined. The conformation of the furan­ose ring can be described as 58% ideal envelope OE conformer and 42% ideal twisted OT1 conformer. The 1,3-dioxane ring adopts a chair conformation with the anhydro-O atom pointing upwards. Both phenyl rings are quasi-perpendicular to the mean plane of the furan­ose ring. The hydrogen bonding is intermolecular and consists of infinite chains parallel to the a axis.

The synthesis of enantiomerically pure decalinic structures, advanced intermediates for the synthesis of the hexahydronaphtalen part of mevinic acids, is described. The key steps are the intramolec...

The methyl group in ( R )-3,5- O -benzylidene- l - rhamnono -1,4-lactone 2 , prepared from l -rhamnose 1 in 41% yield without need for chromatography, is axial and provides a good example of Mills’ rule that the ‘O-inside’ conformations are, in general, more stable than alternative ‘H-inside’ conformations. The lactone 2 may be converted in two steps in an overall 57% yield to the rhamnono -oxetane 3 , which should be useful in generating oxetane dipeptide isosteres and oxetane β-amino acids and in determining the value of the oxetane ring in inducing secondary structure in small peptidomimetics. Methyl 2,4-anhydro-( S )-3,5- O -benzylidene- l -rhamnonate 11 , in which both the phenyl and methyl groups are equatorial, is slightly more thermodynamically stable than 3 , providing a rare exception to Mills’ rule. X-ray crystal structures of 2 and 11 are reported.

The crystal structure of the title compound, C(24)H(28)O(8), has been determined. The conformation of the furanose ring can be described as 58% ideal envelope (O)E conformer and 42% ideal twisted (O)T(1) conformer. The 1,3-dioxane ring adopts a chair conformation with the anhydro-O atom pointing upwards. Both phenyl rings are quasi-perpendicular to the mean plane of the furanose ring. The hydrogen bonding is intermolecular and consists of infinite chains parallel to the a axis.

Tri-O-acetylglucal is the starting material of a new route to chiral highly oxygenated cis decalinic structures by tandem IMDA-Ferrier carbocyclization reactions, single-crystal X-ray analysis of one of these aldol structures is performed.

Communication orale

Poster

Poster

International audience; Le squelette des peptoïdes dérive de celui des peptides par déplacement des chaînes latérales des carbones Cα vers les azotes d'amide. Ce principe a été appliqué aux β-peptides pour conduire aux β-peptoïdes et récemment d'autres architectures de type peptoïde, telles que les α,β-peptoïdes, arylopeptoïdes et N-hydroxy/alcoxy-peptoïdes ont été rapportées dans la littérature. Cette revue dresse un bilan sur les peptoïdes et les nouvelles familles de composés apparentées, tant du point de vue de leur synthèse que de leur préférence conformationnelle. Une mise au point bibliographique est également apportée sur les récentes avancées en termes de contrôle de la géométrie cis/trans des amides N,N-disubstitués des peptoïdes.

International audience; This paper describes the development of a highly convenient solution-phase methodology using volatile amines for the synthesis of β-, α,β- and α-tetrapeptoids, as an alternative to solid-phase technologies. Column chromatographic purifications are reduced to a minimum and the majority of the intermediates are purified by filtration and/or evaporation. The method is amenable to gram-scale synthesis of peptoids, and post-modification of a model peptoid by successive and selective ligations, using click thiol-ene coupling, and copper-catalysed azide-alkyne cycloaddition is demonstrated

International audience; The design of multivalent glycoconjugates has been developed over the past decades to obtain high-affinity ligands for lectin receptors. While multivalency frequently increases the affinity of a ligand for its lectin through the so-called “glycoside cluster effect”, the binding profiles towards different lectins have been much less investigated. We have designed a series of multivalent galactosylated glycoconjugates and studied their binding properties towards two lectins, from plant and bacterial origins, to determine their potential selectivity. The synthesis was achieved through copper(I)-catalysed azide–alkyne cycloaddition (CuAAC) under microwave activation between propargylated multivalent scaffolds and an azido-functionalised carbohydrate derivative. The interactions of two galactose-binding lectins from Pseudomonas aeruginosa (PA-IL) and Erythrina cristagalli (ECA) with the synthesized glycoclusters were studied by hemagglutination inhibition assays (HIA), surface plasmon resonance (SPR) and isothermal titration microcalorimetry (ITC). The results obtained illustrate the influence of the scaffold's geometry on the affinity towards the lectin and also on the relative potency in comparison with a monovalent galactoside reference probe

International audience; We describe the qualitative and quantitative analysis of the complexation properties towards cations of a cyclic peptoid hexamer composed of alternating α- and β-peptoid monomers, which bear exclusively chiral (S)-phenylethyl side chains (spe) that have no noticeable chelating properties. The binding of a series of monovalent and divalent cations was assessed by 1H NMR, circular dichroism, fluorescence and molecular modelling. In contrast to previous studies on cations binding by 18-membered α-cyclopeptoid hexamers, the 21-membered cyclopeptoid cP1 did not complex monovalent cations (Na+, K+, Ag+) but showed selectivity for divalent cations (Ca2+, Ba2+, Sr2+ and Mg2+). Hexacoordinated C-3 symmetrical complexes were demonstrated for divalent cations with ionic radii around 1 Å (Ca2+ and Ba2+), while 5-coordination is preferred for divalent cations with larger (Ba2+) or smaller ionic radii (Mg2+).

Peptoids (N-substituted glycine oligomers) are an important class of foldamers capable of adopting a range of unique secondary structures based on the cis/trans conformation of their constituting main chain tertiary amide bonds. The folding mode of peptoid oligomers in orderly secondary structures and their conformational stability are closely related to their sequence. In this context, my work has focused on the development of new peptoid oligomer sequences as chemical platforms for the topological presentation of photosensitizer agents (phthalocyanin/porphyrin). A first important part of the thesis concerned an in-depth study of the conformation of oligopeptoids. We have developed Polyproline I (PPI) helical structured peptoids with high conformational stability from chiral and achiral aliphatic units. Helical peptoids have been conjugated to one or two macrocyclic photosensitizers. In a second part, cyclic peptoids with functionalpendant side chains have been conceived for the presentation of photosensitizers. Various backbones (α, β and α,β-peptoid) were considered to obtain conjugated molecules displaying diverse ring sizes and topologies., Les peptoïdes (oligomères de glycine N-substituées) sont une classe importante de foldamères capables d'adopter une gamme de structures secondaires uniques basées sur les géométries cis/trans de leurs liaisons amides tertiaires. Le mode de repliement des chaînes peptoïdes en structure ordonnée et leur stabilité conformationnelle sont étroitement liés à la séquence. Dans ce contexte, mon travail s'est principalement focalisé sur la conception de nouvelles séquences d’oligomères peptoïdes pouvant servir de plateformes présentatrices de macrocycles photosensibilisateurs (phtalocyanines/porphyrines). Une première partie importante de la thèse a porté sur la conformation des oligopeptoïdes. Nous avons élaboré des peptoïdes structurés en hélice de type polyproline I (PPI) et présentant une très grande stabilité conformationnelle à partir d’unités aliphatiques chirales et achirales. Dans une seconde grande partie, des hélices de type PPI possédant des chaînes latérales fonctionnelles ont été construites et conjuguées à un ou deux macrocycles phtalocyanines/porphyrines. Nous avons également synthétisé des peptoïdes cycliques en tant que plateformes présentatrices de photosensibilisateurs. Différents squelettes (α, β et α,β-peptoïde) ont été envisagés pour obtenir après conjugaison des édifices présentant des tailles de cycles et des topologies différentes.

Living organisms produce antimicrobial peptides (AMPs) to protect themselves against microbes.The growing problem of antimicrobial resistance calls for new therapeutic strategies and the natural AMPs have shown ground-breaking potential to address that issue. They show broad-spectrum activity and their main mechanism of action by bacterial cell membrane disruption implies low emergence of resistance which makes them potent candidates for replacing conventional antibiotics. Nevertheless, few hurdles are impeding their use, notably poor bioavailability profile. Some of these limitations can be overcome by developing peptidomimetics of AMPs which exhibit antibacterial activities together with enhanced therapeutic potential. Peptoids (i.e. N-alkyl glycine oligomers) adopting cationic amphipathic helical structures are mostly competent AMP mimetics. From a conformational point of view, peptoids are fundamentally more flexible than peptides primarily due to the cis/trans isomerism of N,N-disubstituted amides but studies in this area have shown that cis amide conformation can be controlled by careful choice of side-chain to set a PolyProline I-type helical structure of peptoids. In this thesis, the genesis of novel amphipathic cationic peptoids carrying cis-directing tert-butyl and/or triazolium-type side-chains and their untapped potential to act against bacteria will be discussed comprehensively. First, the solutionphase synthesis of tert-butyl-based oligomers was developed. Second, novel method of solid-phase submonomer synthesis was optimised to access 1,2,3-triazolium-based oligomers. Then, the synthesised cationic oligomers were evaluated for their antibacterial potential, followed by antibiofilm activity and cell selectivity assays. In the end, to have insights on the mode of action of amphipathic peptoids, microscopy was carried out., Les organismes vivants produisent des peptides antimicrobiens (PAMs) pour se protéger contre les microbes. La résistance croissante aux antibiotiques nécessite le développement de nouvelles stratégies thérapeutiques et les PAMs sont des candidats prometteurs pour résoudre ce problème. Ils possèdent une activité à large spectre et leur principal mécanisme d'action par perméation de la membrane engendre peu de phénomènes de résistance. Néanmoins, leur faible biodisponibilité empêche leur utilisation. Certaines limitations peuvent être surmontées en développant des mîmes de PAMs qui conservent leur activité mais avec un potentiel thérapeutique accru. Les peptoïdes (oligomères de N-alkylglycine) structurés en hélice cationique amphiphile sont de bons mimes de PAMs. Les peptoïdes sont plus flexibles que les peptides en raison de l'isomérie cis/trans des amides N,N-disubstitués ; cependant la conformation des amides peut être contrôlée par un choix judicieux des chaînes latérales. Le but de cette thèse est d'étudier l'influence de chaînes latérales(hydrophobes ou cationiques) bloquant la conformation des amides en cis et induisant une structure hélicoïdale de type PolyProline I (PPI) robuste, sur l’activité antibactérienne et la sélectivité de peptoïdes. La conception, la synthèse et l’étude conformationnelle de nouveaux oligomères peptoïdes cationiques portant des chaînes latérales de type tert-butyle et/ou triazolium ont été réalisées. Dans un premier temps, la synthèse en solution d'oligomères à base de tert-butyle a été développée puis une stratégie de synthèse en phase solide a été mise en place pour accéder aux oligomères à base de 1,2,3-triazolium. Ensuite, ces nouveaux oligomères ont été évalués pour leur activité vis à vis d’un panel de bactéries Gram-positive et Gram-négative, leur l'activité antibiofilm et leur sélectivité cellulaire. Enfin, pour visualiser les effets des peptoïdes amphiphiles sur les bactéries, une étude de microscopie a été réalisée.

Tumor-Associated Carbohydrate Antigen (TACAs) are considered as cancer cells markers. The development of synthetic vaccine candidates which are able to induce a robust immune response against these TACAs is a field of great interest since many years. In this context, my work has been focused mainly on the design of a three-component vaccine candidate with the ability to activate specifically dendritic cells, T H cells and B cells. The first part of the thesis consisted in making a deep study on the submonomer and monomer methods for solution-phase synthesis of a β-tripeptoid O-α-GalNAc scaffold (B epitope). Its role is to mimic the Tn (GalNAc-α-O-Ser/Thr) trimeric cluster which is naturally present on tumor cells surface. To strengthen the stimulation of the immune system, a TLR7 agonist (receptor express by dendritic cells) has been, firstly, coupled through an amino-caproic acid spacer. The vaccine candidate has been next completed by conjugation with the OVA 323- 339 peptide (TH epitope) using the Copper-catalized Alkyne-Azide Cycloaddition (CuAAC). Finally, the capacity of this construction to generate anti-Tn response have been evaluated by the groupe of C. Leclerc of Institut Pasteur of Paris. At the same time, we have also developed conditions for multivalent ligations using thiol-ene coupling (TEC) to obtain a β-tripeptoid S-α-GalNAc scaffolds., Les antigènes saccharidiques associés aux tumeurs (TACAs) sont considérés comme des marqueurs de cellules tumorales. Le développement de candidats vaccins synthétiques capables d'induire des réponses immunitaires robustes dirigées contre ces TACAs est un vaste champ d'investigation depuis de nombreuses années. Dans cette optique, mon travail s'est principalement focalisé sur la conception d'un candidat vaccin à trois composantes qui peut activer spécifiquement les cellules dendritiques, les cellules TH et les cellules B. La première partie de la thèse consistait à effectuer une étude approfondie des méthodes submonomère et monomère en solution pour accéder à une plateforme β-tripeptoïde O-α-GalNAc (épitope des cellules B), servant de mime du cluster trimérique de l'antigène Tn (GalNAc-α-O-Ser/Thr). Pour renforcer la stimulation du système immunitaire, un agoniste du récepteur Toll 7 (TLR7) préalablement synthétisé (exprimé par les cellules dendritiques) a été ensuite couplé à cette plateforme par l'intermédiaire de l'acide amino-caproïque, pris comme espaceur. L'édifice candidat vaccin a ensuite été complété par conjugaison au peptide OVA 323-339 (épitope des cellules TH ) grâce à la réaction de cycloaddition 1,3-dipolaire CuAAC. Enfin, l'aptitude du candidat vaccin à induire une réponse anti-Tn a été évaluée par l'équipe du Pr. C. Leclerc de l'Institut Pasteur de Paris. En parallèle de ces études, nous avons mis au point des conditions de ligation multivalente par couplage thiol-ène (TEC) pour l'obtention de peptoïdes S-glycosylés.

β-peptides show a high stability towards proteolytic and metabolic processes. This work has been focused mainly on their use as multivalent platforms for the presentation of various carbohydrates, in particular tumor specific antigenic carbohydrate patterns, the socalled TACAs (Tumor-Associated Carbohydrate Antigen). TACAs, and among them the Tn antigen (GalNAc-α-O-Ser/Thr), are considered as cancer cells markers which can be integrated into fully synthetic structures aimed at mimicking tumor cells surface to induce an antitumoral immunologic response. In the first part of the thesis, the synthesis of β-peptides glycoconjugates, using the Copper-catalyzed Alkyne-Azide Cycloaddition (CuAAC) has been investigated. These glycoconjugates containing up to six carbohydrate moities have been elaborated from azide- and alkyne-functionnalized β-peptides prepared from aspartic acid. The trimers of these glycoconjugated β-peptides were also coupled to biotine through an aminocaproic spacer and the constructs were tested for their antigenicity. Besides this, β- peptides exhibit a high tendancy to adopt secondary structures. That's why a conformational analysis of the β-peptide oligomers synthesized was carried out to determine the nature of a potential structuration., Les bêta-peptides montrent une grande stabilité métabolique et protéolytique. Ce travail s'est principalement focalisé sur leur utilisation en tant que plateformes multivalentes pour la présentation de "sucres" et en particulier d'antigènes saccharidiques spécifiques des tumeurs, connus sous le nom de TACAs (Tumor-Associated Carbohydrate Antigen). Les TACAs, et parmi eux l'antigène Tn (GalNAc-Alpha-O-Ser/Thr), sont considérés comme des marqueurs des cellules tumorales qui peuvent être intégrés dans des structures synthétiques destinées à mimer la surface des cellules cancéreuses en vue d'induire une réponse immunitaire antitumorale. Dans la première partie de la thèse, nous avons étudié la synthèse de bêta-peptides glycoconjugués, obtenus par cycloaddition 1,3-dipolaire catalysée au cuivre entre un alcyne et un azoture (CuAAC - Copper-catalysed Alkyne-Azide Cycloaddition). Ces glycoconjugués, présentant jusqu'à six unités saccharidiques, ont été élaborés à partir de bêta-peptides fonctionnalisés par des groupes azoture ou alcyne, préparés au départ d'acide aspartique. Les trimères glycoconjugués ont également été couplés à de la biotine, par l'intermédiaire d'un espaceur (d'acide aminocaproïque) et l'antigénécité de ces édifices a été testée. Les bêta-peptides présentent également une tendance prononcée à adopter des structurations secondaires. C'est pourquoi les oligomères synthétisés ont été étudiés d'un point de vue conformationnel afin de déterminer la nature d'une éventuelle préférence conformationnelle

The objective of this work was the design and synthesis of short glycopeptides that can fold into well defined and typical secondary structures. b-Peptides frameworks are capable of forming structurally well-defined and predictable structures on short sequences and were therefore chosen for our purpose. In addition, b-peptide backbones are resistant to peptidases and proteases. We were interested in preparing such artificial oligomers modified, like a vaste majority of proteins, by linkage to carbohydrates. The study of carbohydrate-functionalized b-peptides is expected to bring important information concerning the structural stability of such glycoconjugates. In this context, we have presented the homo-oligomerisation of the unnatural glyco-amino acid into a new class of carbopeptoïds. The conformational preference of this first class of oligomers has been assessed by spectroscopic techniques (NMR, IR, CD) and calculations. Another part of this work concerned the synthesis of C-glycosyl-b3-amino acids and O-glycosyl-b3-amino acids as building blocks in the construction of glyco-b-peptides. Finally, we were interested in the synthesis of a new class of glyco-b-amino acids analogues, which are called Na-(C-glycosyl)-hydrazino acids.; Ce travail concerne la synthèse de courts glycopeptides pouvant adopter une structuration secondaire définie. Les chaînes b-peptidiques peuvent se structurer sur de courtes séquences oligomèriques. C'est pourquoi les b-peptides ont été choisis pour réaliser ce travail, de plus ils sont résistants aux peptidases et aux protéases. Nous nous sommes intéressés à la préparation de ce type d'oligomères artificiels modifiés en les liants à des unités sucres. Nous souhaitons étudier l'influence de la glycosylation de chaînes b-peptidiques, et déterminer si la structuration est conservée lorsque la chaîne est « décorée » par des résidus sucres. Dans ce contexte, nous avons présentés l'homo-oligomérisation de glyco-amino acide artificiel formant une nouvelle classe de carbopeptoïdes. Une analyse conformationnelle par modélisation moléculaire et par des techniques spectroscopiques (RMN, DC, IR) a été menée sur cette première classe d'oligomères. Un second aspect de notre travail à consisté à synthétiser des C-glycosyl-b3-amino acides et des O-glycosyl-b3-amino acides. Ces monomères sont, en effet, des unités centrales dans la formation de glycosyl-b-peptides. Finalement ; nous nous sommes intéressés à la synthèse d'une nouvelle classe d'analogues de glyco-b-amino acide appelée les Na-(C-glycosyl)-hydrazino acides.

The objective of this work was the design and synthesis of short glycopeptides that can fold into well defined and typical secondary structures. b-Peptides frameworks are capable of forming structurally well-defined and predictable structures on short sequences and were therefore chosen for our purpose. In addition, b-peptide backbones are resistant to peptidases and proteases. We were interested in preparing such artificial oligomers modified, like a vaste majority of proteins, by linkage to carbohydrates. The study of carbohydrate-functionalized b-peptides is expected to bring important information concerning the structural stability of such glycoconjugates. In this context, we have presented the homo-oligomerisation of the unnatural glyco-amino acid into a new class of carbopeptoïds. The conformational preference of this first class of oligomers has been assessed by spectroscopic techniques (NMR, IR, CD) and calculations. Another part of this work concerned the synthesis of C-glycosyl-b3-amino acids and O-glycosyl-b3-amino acids as building blocks in the construction of glyco-b-peptides. Finally, we were interested in the synthesis of a new class of glyco-b-amino acids analogues, which are called Na-(C-glycosyl)-hydrazino acids., Ce travail concerne la synthèse de courts glycopeptides pouvant adopter une structuration secondaire définie. Les chaînes b-peptidiques peuvent se structurer sur de courtes séquences oligomèriques. C'est pourquoi les b-peptides ont été choisis pour réaliser ce travail, de plus ils sont résistants aux peptidases et aux protéases. Nous nous sommes intéressés à la préparation de ce type d'oligomères artificiels modifiés en les liants à des unités sucres. Nous souhaitons étudier l'influence de la glycosylation de chaînes b-peptidiques, et déterminer si la structuration est conservée lorsque la chaîne est « décorée » par des résidus sucres. Dans ce contexte, nous avons présentés l'homo-oligomérisation de glyco-amino acide artificiel formant une nouvelle classe de carbopeptoïdes. Une analyse conformationnelle par modélisation moléculaire et par des techniques spectroscopiques (RMN, DC, IR) a été menée sur cette première classe d'oligomères. Un second aspect de notre travail à consisté à synthétiser des C-glycosyl-b3-amino acides et des O-glycosyl-b3-amino acides. Ces monomères sont, en effet, des unités centrales dans la formation de glycosyl-b-peptides. Finalement ; nous nous sommes intéressés à la synthèse d'une nouvelle classe d'analogues de glyco-b-amino acide appelée les Na-(C-glycosyl)-hydrazino acides.