Expanding the scope of cyclopropene reporters for the detection of metabolically engineered glycoproteins by Diels–Alder reactions

• Anne-Katrin Späte,
• Verena F. Schart,
• Julia Häfner,
• Andrea Niederwieser,
• Thomas U. Mayer and
• Valentin Wittmann

Beilstein J. Org. Chem. 2014, 10, 2235–2242, doi:10.3762/bjoc.10.232

• Biology and Konstanz Research School Chemical Biology (KoRS-CB), Universitätsstraße 10, 78457 Konstanz, Germany 10.3762/bjoc.10.232 Abstract Monitoring glycoconjugates has been tremendously facilitated by the development of metabolic oligosaccharide engineering. Recently, the inverse-electron-demand

• higher fluorescence staining of cell-surface glycoconjugates, the glucosamine derivative gave higher labeling efficiency with protein preparations containing also intracellular proteins. Keywords: bioorthogonal chemistry; carbohydrates; cyclopropenes; inverse-electron-demand Diels-Alder reactions

• ; metabolic oligosaccharide engineering; Introduction The glycan chains of glycoproteins and lipids have been shown to be involved in numerous biological recognition and regulation events [1]. Glycan research, especially the visualization of glycoconjugates in vitro and in vivo, has significantly profited

Expeditive synthesis of trithiotriazine-cored glycoclusters and inhibition of Pseudomonas aeruginosa biofilm formation

• Meriem Smadhi,
• Sophie de Bentzmann,
• Anne Imberty,
• Marc Gingras,
• Raoudha Abderrahim and
• Peter G. Goekjian

Beilstein J. Org. Chem. 2014, 10, 1981–1990, doi:10.3762/bjoc.10.206

• the hexavalent benzene cluster [30], which may be attributed to differences in rigidity and hydrophobicity between the two systems [25]. It thus appears that the direct diaryl sulfide bridge presents a more optimal degree of semi-rigidity. The affinities of the designed glycoconjugates with lecA and

Bifunctional dendrons for multiple carbohydrate presentation via carbonyl chemistry

• Davide Bini,
• Francesco Nicotra and
• Laura Cipolla

Beilstein J. Org. Chem. 2014, 10, 1686–1691, doi:10.3762/bjoc.10.177

• the development of smart biomaterials for regenerative medicine [9][10][11][12]. Beside the variation of carbohydrate residues in glycoconjugates, a key issue in the recognition process is their spatial topographical presentation eliciting high affinity recognition events. In order to better

• understand these phenomena, dendrimers and dendrons have been developed to provide multivalent glycoconjugates [13][14]. Here, we propose the synthesis of novel dendron structures which allow for the multivalent conjugation of carbohydrates via carbonyl chemistry. Results and Discussion The

Clicked and long spaced galactosyl- and lactosylcalix[4]arenes: new multivalent galectin-3 ligands

• Silvia Bernardi,
• Paola Fezzardi,
• Gabriele Rispoli,
• Stefania E. Sestito,
• Francesco Peri,
• Francesco Sansone and
• Alessandro Casnati

Beilstein J. Org. Chem. 2014, 10, 1672–1680, doi:10.3762/bjoc.10.175

• formation of the tetraazidocalixarene derivative 12 (1 h, 75% yield). The CuAAC conjugation reaction was carried out following exactly the same procedure as for compound 9 and allowed the isolation of 13 in very high yields (81%). Glycoconjugates 9 and 13 were fully characterized by 1H and 13C NMR

• macrocycle arms to the saccharide units. On the basis of the comparison between the efficiency of the conjugation steps bringing to glycoconjugates 9 and 13 (yields >80% in both cases) and contrary to the observation by Marra et al. [37], we could not collect any evidence for an autocatalytic effect in the

Photoswitchable precision glycooligomers and their lectin binding

• Daniela Ponader,
• Sinaida Igde,
• Marko Wehle,
• Katharina Märker,
• Mark Santer,
• David Bléger and
• Laura Hartmann

Beilstein J. Org. Chem. 2014, 10, 1603–1612, doi:10.3762/bjoc.10.166

• planar form (E-isomer, thermodynamically favored) and a more compact and twisted state (Z-isomer). Monovalent [15] and divalent [16] photoswitchable glycoconjugates described in the literature showed a different binding behavior depending on the configuration of the azobenzene (E or Z), although the

• )-5 Z-isomers is anticipated to be very similar since their two azo units were found to operate independently. The long-lived Z-forms of these glycoconjugates allows for a convenient handling of the PSS mixtures and a precise measurement of their binding affinities. Lectin binding studies Competition

Orthogonal dual thiol–chloroacetyl and thiol–ene couplings for the sequential one-pot assembly of heteroglycoclusters

• Michele Fiore,
• Gour Chand Daskhan,
• Baptiste Thomas and
• Olivier Renaudet

Beilstein J. Org. Chem. 2014, 10, 1557–1563, doi:10.3762/bjoc.10.160

• carbohydrate–protein interactions are complex mechanisms that play key roles in biology [1]. To decipher, exploit or inhibit these recognition processes, a large variety of synthetic multivalent glycoconjugates have been developed over the last decade [2][3][4]. For a long time, these structures have

Why a diaminopyrrolic tripodal receptor binds mannosides in acetonitrile but not in water?

• Diogo Vila-Viçosa,
• Oscar Francesconi and
• Miguel Machuqueiro

Beilstein J. Org. Chem. 2014, 10, 1513–1523, doi:10.3762/bjoc.10.156

• of the most abundant sugars in glycoconjugates [9][10]. In 2011, Roelens’ group [11][12][13] synthetized and tested a chiral diaminopyrrolic tripodal receptor that showed high binding affinities to mannosides (Figure 1). This particular receptor is significantly more active in acetonitrile (ACN) than

Bis(β-lactosyl)-[60]fullerene as novel class of glycolipids useful for the detection and the decontamination of biological toxins of the Ricinus communis family

• Hirofumi Dohi,
• Takeru Kanazawa,
• Akihiro Saito,
• Keita Sato,
• Hirotaka Uzawa,
• Yasuo Seto and
• Yoshihiro Nishida

Beilstein J. Org. Chem. 2014, 10, 1504–1512, doi:10.3762/bjoc.10.155

• ; ricin; Introduction Carbohydrate-binding proteins (lectins) and proteotoxins, e.g., verotoxins [1][2] and cholera toxins [3], can cause serious damages to human cells. The carbohydrate binding proteins are able to interact with cell-surface glycoconjugates such as glycoproteins and glycolipids to

• aggregate the cells. Proteotoxins penetrate into the target cells after binding with glycoconjugates and disturb vital cell functions. Ricin, a proteotoxin isolated from the castor bean of the Ricinus communis family, is one of the strongest biological toxins and is registered as a scheduled compound in the

Postsynthetic functionalization of glycodendrons at the focal point

• Thisbe K. Lindhorst and
• Katharina Elsner

Beilstein J. Org. Chem. 2014, 10, 1482–1487, doi:10.3762/bjoc.10.152

• Thisbe K. Lindhorst Katharina Elsner Otto Diels Institute of Organic Chemistry, Christiana Albertina University of Kiel, Otto-Hahn-Platz 3–4, D-24098 Kiel 10.3762/bjoc.10.152 Abstract Glycodendrons are multivalent glycoconjugates bearing an orthogonal functional group at the focal point of the

• etherification, thiol-ene reaction and in particular olefin cross metathesis. Keywords: amphiphilic glycomimetics; cross metathesis; glycodendrons; multivalent glycoconjugates; multivalent glycosystems; Introduction In addition to nucleic acids and proteins, molecular life is based on a third important class

• frequently applied for the synthesis of multivalent glycoconjugates [6]. Dendrons resemble a branched fragment of a whole dendrimer with an orthogonal functional group (FG) at the focal point of the molecular fragment (Figure 1a). This molecular architecture comprises the possibility to anchor a multivalent

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• recognized as immunodominant epitopes in antigenic glycoconjugates [14]. Carbohydrates participate in molecular recognition events such as host–pathogen interactions, responsible for mammal infections, and are candidates for chemotherapy [15]. Moreover, synthesis of multivalent carbohydrate ligands provide

Synthesis of the first examples of iminosugar clusters based on cyclopeptoid cores

• Mathieu L. Lepage,
• Alessandra Meli,
• Anne Bodlenner,
• Céline Tarnus,
• Francesco De Riccardis,
• Irene Izzo and
• Philippe Compain

Beilstein J. Org. Chem. 2014, 10, 1406–1412, doi:10.3762/bjoc.10.144

• ][16][17], appear as promising scaffolds for the synthesis of glycoconjugates of biological interest [14][15][16][17][18]. Combination of these advantages has led to many examples of biologically active peptoids [19][20][21]. So far, some syntheses of N-, O-, C- and S-linked glycopeptoids have been

Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

• Melanie Rauschenberg,
• Eva-Corrina Fritz,
• Christian Schulz,
• Tobias Kaufmann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 1354–1364, doi:10.3762/bjoc.10.138

• glycosystems; peptides; Introduction In comparison to proteins and nucleic acids, carbohydrates have traditionally received less attention in the scientific community. However, it is increasingly apparent that carbohydrates and glycoconjugates are involved in a multitude of physiological and pathological

Design and synthesis of multivalent neoglycoconjugates by click conjugations

• Feiqing Ding,
• Li Ji,
• Ronny William,
• Hua Chai and
• Xue-Wei Liu

Beilstein J. Org. Chem. 2014, 10, 1325–1332, doi:10.3762/bjoc.10.134

• ][27][28][29][30][31]. The α-GalNAc-linked glycopeptides, α-N-glycosidically linked to the polypeptide chain through the amido nitrogen of an asparagine residue at the N-terminal [32], were found to be the most important semi-synthetic glycoconjugates, usually modified from their naturally occurring

• monovalent affinities of carbohydrate monosaccharides are comparatively low and weak. To enhance this multivalent effect, thereby increasing the binding efficiencies of carbohydrates with the coupling counterparts, there has been a constant development of new glycoconjugates such as glycodendrimers [57

• glycoscience, because triazole-linked glycoconjugates can exhibit very interesting biological properties, offering a convenient access toward oligosaccharides, glycopeptide mimics, or multivalent carbohydrate systems [40][41][42][43][44][45][46][47][48]. Their further application in molcecular biosystems is

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• -benzoate protected L-amicetose and a cinerulose derivative protected at C5 and C1. Keywords: carbohydrates; de novo synthesis; lactate; metathesis; ruthenium; Introduction Many drugs and bioactive natural products are glycoconjugates, which contain an aglycon part linked through glycosidic bonds to one

• apparently identical catalysts which are often designated just as “10 wt % Pd on carbon” may vary dramatically. Structures of kigamicin B and aclacinomycin A as representative examples for antineoplastic glycoconjugates. RCM-isomerization approach to L-amicetal 4 and alternative CM approaches to L-amicetose

Molecular architecture with carbohydrate functionalized β-peptides adopting 3₁₄-helical conformation

• Nitin J. Pawar,
• Navdeep S. Sidhu,
• George M. Sheldrick,
• Dilip D. Dhavale and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2014, 10, 948–955, doi:10.3762/bjoc.10.93

• report well-defined tetravalent mannose glycoconjugates on a cyclic peptide which show specific binding with concanavalin A [29]. Further, the ternary type-II polyproline helix is used for the structurally defined presentation of sugar units [34], and similarly the β-peptides provide a suitable

Synthesis of enantiopure sugar-decorated six-armed triptycene derivatives

• Paola Bonaccorsi,
• Maria Luisa Di Gioia,
• Antonella Leggio,
• Lucio Minuti,
• Teresa Papalia,
• Carlo Siciliano,
• Andrea Temperini and
• Anna Barattucci

Beilstein J. Org. Chem. 2013, 9, 2410–2416, doi:10.3762/bjoc.9.278

• fully characterized. Keywords: azide derivatives; click chemistry; glycoconjugates; 2-propyn-1-yl β-D-glycopyranosides; triptycene; Introduction Triptycene (1), with its three arene units fused to the bicyclo[2.2.2]octa-2,5,7-triene system appears as a paddle wheel on closer inspection (Figure 1). The

• cluster effect [7][8][9][10][11]. These glycoconjugates showed their potentialities not only in the interpretation of molecular recognition events but also in biotechnological, pharmaceutical and medical fields [12]. Our research interest is focused on the synthesis of new glycoconjugates and the study of

• applications not only as glycoconjugates in glycochemistry, but also as interesting candidates for host–guest interactions by presenting a rigid lipophilic core surrounded by hydrophilic sugar moieties assembled on a rotor skeleton. The six-armed sugar-decorated triptycene derivatives might constitute a new

Gold-catalyzed glycosidation for the synthesis of trisaccharides by applying the armed–disarmed strategy

• Abhijeet K. Kayastha and
• Srinivas Hotha

Beilstein J. Org. Chem. 2013, 9, 2147–2155, doi:10.3762/bjoc.9.252

• glycoconjugates [24], carbohydrate epitopes present on the cell surface of infectious bacteria [25], glycopolypeptides [26], glycopolyacrylates [27], and glycomimetics [28]. The remarkable reactivity and chemoselectivity have also attracted other groups to investigate gold catalysts for glycosidation [29][30][31

Straightforward synthesis of a tetrasaccharide repeating unit corresponding to the O-antigen of Escherichia coli O16

• Manas Jana and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 1757–1762, doi:10.3762/bjoc.9.203

• virulence property of the pathogen, several reports appeared in the past on the development of glycoconjugate based therapeutics against bacterial infections [10][11][12]. Detailed biological studies of the glycoconjugates require a significant quantity of the oligosaccharides, which is difficult to isolate

Glycosylation efficiencies on different solid supports using a hydrogenolysis-labile linker

• Mayeul Collot,
• Steffen Eller,
• Markus Weishaupt and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 97–105, doi:10.3762/bjoc.9.13

• issues. Cleavage of the linker by hydrogenolysis results in a free amine functionality for the immobilization of oligosaccharides on glycan arrays or for the synthesis of glycoconjugates. Hydrogenolysis on a solid support has been used previously in peptide chemistry [37]. In the early 1980s, catalytic

• linker 1. Cleavage by hydrogenolysis from a solid support reveals a conjugation site for the synthesis of glycoconjugates or glycan arrays and simultaneously removes permanent benzyl protecting groups. The linker can be coupled to amino- and chloro-functionalized resins. By placement of insert 2 on amino

S-Fluorenylmethyl protection of the cysteine side chain upon N^α-Fmoc deprotection

• Johannes W. Wehner and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2012, 8, 2149–2155, doi:10.3762/bjoc.8.242

• during N-Fmoc removal. The problem of transprotection can be solved by choosing the appropriate base at appropriate concentrations. Conclusion Glycocysteine/cystine derivatives are versatile building blocks for the synthesis of a wide variety of glycoconjugates, which are thus accessible by, among other

Synthesis of a derivative of α-D-Glcp(1->2)-D-Galf suitable for further glycosylation and of α-D-Glcp(1->2)-D-Gal, a disaccharide fragment obtained from varianose

• Carla Marino,
• Carlos Lima,
• Karina Mariño and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2012, 8, 2142–2148, doi:10.3762/bjoc.8.241

• -Galf-containing glycoconjugates, the mechanisms by which α-D-Galf units are incorporated remain unclear. Penicillium varians is a non-pathogenic fungus that produces varianose, a polysaccharide containing both α- and β-D-Galf units, which can be used as a model for biosynthetic studies on α-D-Galf

Acylsulfonamide safety-catch linker: promise and limitations for solid–phase oligosaccharide synthesis

• Jian Yin,
• Steffen Eller,
• Mayeul Collot and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 2067–2071, doi:10.3762/bjoc.8.232

• revealed during final deprotection serves in the formation of glycoconjugates and glycan microarrays [19]. Synthesis of 10 relied on key intermediates 4 and 6 (Scheme 1). Monobenzylated amine 4 was prepared by reductive amination [20]. An established three-step synthesis starting with hydrocinnamic acid

Antifreeze glycopeptide diastereomers

• Lilly Nagel,
• Carsten Budke,
• Axel Dreyer,
• Thomas Koop and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 1657–1667, doi:10.3762/bjoc.8.190

• proline replacements [5]. These peptides exhibit less antifreeze activity than monosaccharide-substituted AFGP analogues without proline residues. Peptoid glycoconjugates with carbohydrate moieties attached by CuI catalyzed azide-alkyne cycloaddition (CuAAC) were devoid of antifreeze activity [17

The Amadori rearrangement as glycoconjugation method: Synthesis of non-natural C-glycosyl type glycoconjugates

• Katharina Gallas,
• Gerit Pototschnig,
• Florian Adanitsch,
• Arnold E. Stütz and
• Tanja M. Wrodnigg

Beilstein J. Org. Chem. 2012, 8, 1619–1629, doi:10.3762/bjoc.8.185

• conjugation of carbohydrate moieties to suitable amino components. Starting from selected aldoheptoses, which are readily available by means of the Kiliani–Fischer C-elongation reaction of the corresponding aldohexoses, glycoconjugates presenting D-gluco, D-manno and D-galacto as well as GlcNAc motifs have

• been synthesised. Following this strategy, non-natural C-glycosyl type glycoconjugates, which can be utilised as building blocks for the composition of larger molecular constructions, are available by a very short synthetic approach. Keywords: Amadori rearrangement; C-glycosyl type glycoconjugates

• ; carbohydrate elongation; non-natural carbohydrate conjugates; Introduction Glycoconjugates such as glycoproteins, glycopeptides, glycolipids and peptidoglycans are ubiquitous in nature [1]. They are found on cell surfaces and are responsible for processes such as cell–cell interaction, recognition and

High-affinity multivalent wheat germ agglutinin ligands by one-pot click reaction

• Henning S. G. Beckmann,
• Heiko M. Möller and
• Valentin Wittmann

Beilstein J. Org. Chem. 2012, 8, 819–826, doi:10.3762/bjoc.8.91

• azides (see Supporting Information File 1 for full experimental data). According to TLC all reactions (except for B6) proceeded with complete conversion of the amines to the desired glycoconjugates. However, some loss of material during purification of the acetylated chitobiose derivatives by flash

• intermediate diazide 2. Deacetylation of glycoconjugates B1–B6. (a) NaOMe, MeOH. Formation of side-product 5 during the synthesis of 4. Synthesis of glycoclusters B1–B6 using the one-pot procedure for diazo transfer and azide-alkyne cycloaddition. Absolute and relative IC50 values of synthetic ligands C1–C6