A versatile δ-aminolevulinic acid (ΑLA)-cyclodextrin bimodal conjugate-prodrug for PDT applications with the help of intracellular chemistry

• Chrysie Aggelidou,
• Theodossis A. Theodossiou,
• Antonio Ricardo Gonçalves,
• Mariza Lampropoulou and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 2414–2420, doi:10.3762/bjoc.10.251

• hydrophobic cavity [7]. The cyclodextrins (CDs) are a notable family of semi-natural carbohydrate molecules approved as pharmaceutical excipients that improve the solubility and bioavailability of drugs through molecular encapsulation. We demonstrated [6] the conjugate’s (PpIX-CD) bimodal action of

Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

• Laura Morelli,
• Damiano Cancogni,
• Marta Tontini,
• Alberto Nilo,
• Sara Filippini,
• Paolo Costantino,
• Maria Rosaria Romano,
• Francesco Berti,
• Roberto Adamo and
• Luigi Lay

Beilstein J. Org. Chem. 2014, 10, 2367–2376, doi:10.3762/bjoc.10.247

• infections is still unknown. Over the recent years, advances in the synthesis of complex glycans are rendering accessible a variety of carbohydrate antigens with well-defined chemical structure and devoid of bacterial contaminations which could derive from purification of biological materials [21][22][23][24

• excess of unconjugated carbohydrate by precipitation with ammonium sulfate and reconstitution in 10 mM NaPi pH 7.2. The occurrence of conjugation was assessed by SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) and MALDI–TOF mass spectrometry (see Supporting Information File 1). The

• same conjugation chemistry and different carbohydrate structures [26][27]. However, it needs to be taken in consideration that this loading is comparable to that achieved in the preparation of anti-meningococcal vaccines commercially available [37]. Furthermore, a number of 2.5 and 1.7–4.1 sugar

Multivalent glycosystems for nanoscience

• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2014, 10, 2345–2347, doi:10.3762/bjoc.10.244

• this field of research. Now, a third “sweet” Thematic Series is presented in which the borderline between Alice’s Wonderland and real-life applications of carbohydrates has been deliberately crossed. The structural world of natural sugars has been extended towards artificial carbohydrate architectures

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

• found application in MOE, and several dienophiles, such as terminal alkenes [19], isonitriles [20][21], and cyclopropenes [22][23][24], have been incorporated in carbohydrate derivatives and detected by reaction with 1,2,4,5-tetrazines [25] (Scheme 1). An important advantage of the DAinv reaction is the

Indium-mediated allylation in carbohydrate synthesis: A short and efficient approach towards higher 2-acetamido-2-deoxy sugars

• Christopher Albler,
• Ralph Hollaus,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2014, 10, 2230–2234, doi:10.3762/bjoc.10.231

• Christopher Albler Ralph Hollaus Hanspeter Kahlig Walther Schmid Department of Organic Chemistry, University of Vienna, Währingerstrasse 38, 1090 Vienna, Austria 10.3762/bjoc.10.231 Abstract Higher aminosugars are interesting targets in carbohydrate synthesis since these compounds play important

De novo macrolide–glycolipid macrolactone hybrids: Synthesis, structure and antibiotic activity of carbohydrate-fused macrocycles

• Richard T. Desmond,
• Anniefer N. Magpusao,
• Chris Lorenc,
• Jeremy B. Alverson,
• Nigel Priestley and
• Mark W. Peczuh

Beilstein J. Org. Chem. 2014, 10, 2215–2221, doi:10.3762/bjoc.10.229

• . Glycosylation of an available hydroxy group on the macrocycle gave a hybrid macrolide with features common to erythromycin and sophorlipid macrolactone. Weak antibiotic activity (MICs <100 μg/mL) was observed for several of the compounds. Keywords: antibiotic; carbohydrate; exo-anomeric effect; macrolide

• ; structure; synthesis; Introduction In contemporary usage, “macrolide” describes any large ring lactone [1]. It was originally coined, however, with reference to a narrower set of compounds: antimicrobial natural products containing a macrolactone ring adorned with deoxygenated carbohydrate residues [2

• ], have investigated compounds that blend features of macrolides and glycolipid lactones. These natural product-like compounds fuse the carbohydrate ring to the macrocycle rather than connecting them through a glycosidic linkage. Compounds 3 and 4 in Figure 1 illustrate one approach that has been reported

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

• promoting its dissolution is thus particularly appealing. Because the formation of PA biofilm is a complex process partly mediated by the D-galactose-specific lectin lecA (PA-IL) [7][8][9][10] and the L-fucose-specific lectin lecB (PA-IIL) [11][12][13], lectin-carbohydrate interactions can provide a new

• bioactivity of these lectins in host recognition and adhesion in biofilm formation represents an attractive antibacterial strategy, as multivalent carbohydrate motifs on cell surfaces are known to mediate a broad range of cellular and tissue adhesion processes. Carbohydrate recognition in biological systems

• high density of proximate carbohydrate epitopes with limited degrees of freedom onto a sulfurated heteroaromatic scaffold as novel glycosylated asterisk ligands [30]. We have thus designed a simple, yet effective new family of multivalent glycosylated architectures built around a trithiotriazine core

Reaction of selected carbohydrate aldehydes with benzylmagnesium halides: benzyl versus o-tolyl rearrangement

• Maroš Bella,
• Bohumil Steiner,
• Vratislav Langer and
• Miroslav Koóš

Beilstein J. Org. Chem. 2014, 10, 1942–1950, doi:10.3762/bjoc.10.202

• possible mechanism for the Grignard reaction leading to the benzyl→o-tolyl rearrangement is also proposed. Keywords: aldehyde; benzyl versus o-tolyl; carbohydrate; Grignard reaction; rearrangement; X-ray crystallography; Introduction One of the most popular synthetic routes leading to the formation of

• possible the preparation of a series of useful carbohydrate derivatives [1][2][3][4][5][6][7][8]. Despite the demonstrable advantages of the Grignard reaction, there remain, in addition to the recognised drawbacks, some new unexpected impediments limiting its application in the synthesis of branched

• more detailed inspection. Results and Discussion Although 1 and 2 have frequently been used for the introduction of the benzyl group into a carbohydrate molecule [12][13][14][15][16][17][18], the benzyl→o-tolyl rearrangement has, to the best of our knowledge, only been reported once. In this regard

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• Maja Kandziora Hans-Ulrich Reissig Freie Universität Berlin, Institut für Chemie und Biochemie, Takustraße 3, D-14195 Berlin, Germany 10.3762/bjoc.10.182 Abstract An approach to β-D-2-aminotalose- and β-D-2-aminoidose-configured carbohydrate mimetics bearing a phenyl substituent is described

• -couplings to form biphenyl aminopyran or p-terphenyl-linked dimers. Hydrogenolysis afforded new unnatural aminosugar mimetics. Zinc in the presence of acid or samarium diiodide were examined for the N–O bond cleavage in order to obtain the rigid p-terphenyl-linked C-glycosyl dimers. Keywords: carbohydrate

• -glycosides which possess structural and functional aspects of the corresponding carbohydrates, these disadvantages can be overcome, resulting in an improved bioavailability, higher affinities and improved selectivities [8][9][10][11][12][13]. Recent results indicate that divalent rigid carbohydrate

Convergent synthetic methodology for the construction of self-adjuvanting lipopeptide vaccines using a novel carbohydrate scaffold

• Vincent Fagan,
• Istvan Toth and
• Pavla Simerska

Beilstein J. Org. Chem. 2014, 10, 1741–1748, doi:10.3762/bjoc.10.181

• carbohydrate building block was coupled to the self-adjuvanting lipidic moiety (three lipidated Fmoc-lysines) on solid support. Four copies of a group A streptococcal B cell epitope (J8) were then conjugated to the glyco-lipopeptide using a copper-catalyzed cycloaddition reaction. The approach was elaborated

• severe GAS related problems are post-streptococcal rheumatic fever and rheumatic heart disease, which are responsible for over half a million deaths annually [14]. Previously, we developed methodologies for the synthesis of carbohydrate building blocks as scaffold carriers of multiple B cell epitopes

• derived from GAS. The vaccine constructs consisted of the LCP adjuvanting moiety, and a carbohydrate core bearing four copies of a GAS B cell epitope [11][15][16][17][18]. When administered to B10.BR (H-2k) mice, the carbohydrate-based LCP vaccines elicited high serum IgG antibody titres [11]. One of the

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• asymmetric Biginelli reaction have been reviewed [97]. The reaction has been employed in the synthesis of C-nucleosides with 3,4-dihydropyrimidin-2(1H)-one or 3,4-dihydropyrimidin-2(1H)-thione as the nucleobase mimic. Up to date, depending on the role of the carbohydrate component in the reaction, C

• -nucleosides bearing the carbohydrate moiety at the position of N-1, C-4 or C-6 of the nucleobase mimic were synthesized. Starting from sugar aldehyde substrates 73, Molina et al. synthesized a series of compounds 74 bearing the carbohydrate moiety at the C-4 carbon atom of the 3,4-dihydropyrimidin-2(1H)-one

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

• carbonyl groups can be exploited for carbohydrate functionalization [15][16] by reductive amination, oxime or hydrazone formation to yield suitably functionalized saccharides (Figure 1). Given the relevance of L-fucose in mammal oligosaccharides, α-L-(2-aminoethyl) fucoside [17] and α-O-L

Concise total synthesis of two marine natural nucleosides: trachycladines A and B

• Haixin Ding,
• Wei Li,
• Zhizhong Ruan,
• Ruchun Yang,
• Zhijie Mao,
• Qiang Xiao and
• Jun Wu

Beilstein J. Org. Chem. 2014, 10, 1681–1685, doi:10.3762/bjoc.10.176

• ), nucleoside 3 could be synthesized by using 1,2,3,5-tetra-O-benzoyl-2-C-methyl-D-ribofuranose (5) as a carbohydrate acceptor by a Vorbrüggen glycosylation with the corresponding silylated nucleobases and a Lewis acid as a catalyst. As the key intermediate for the preparation of the anti-HCV nucleoside

• valopicitabine (NM-283) [21][22] and related nucleosides, there are suitable methodologies for the synthesis of carbohydrate 5 [23]. After the selective deoxygenation of the C-5′ hydroxy group of nucleosides 3, trachycladine A and B could be afforded. According to the preliminary results from our lab

• (unpublished results), the deoxygenation procedure of the C-5′ hydroxy group was accompanied by several undesired side reactions. Then we turned to synthetic route (B), which utilizes carbohydrate 4 as a Vorbrüggen glycosylation donor. Firstly, without the deoxygenation of the C-5′ hydroxy group at the late

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

• plasmon resonance; Introduction Lectins are carbohydrate-binding proteins (CBP) [1][2][3] without any catalytic or immunogenic activity. In the latest decades, they attracted an increasing interest due to their involvement in a series of fundamental biological processes such as cell adhesion, cell

Expedient synthesis of 1,6-anhydro-α-D-galactofuranose, a useful intermediate for glycobiological tools

• Luciana Baldoni and
• Carla Marino

Beilstein J. Org. Chem. 2014, 10, 1651–1656, doi:10.3762/bjoc.10.172

• ; Introduction Anhydro sugars are formed by the intramolecular elimination of a water molecule, with the simultaneous formation of a new heterocyclic ring of different size. They are valuable intermediates not only in carbohydrate synthesis, but also as starting materials for other natural and non-natural

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

• ; multivalent glycosystems; photoswitch; precision polymer; Introduction Carbohydrate ligand–receptor interactions underpin many important processes in biology, for example in host-pathogen interactions [1][2]. Although monosaccharides usually exhibit only low binding affinities, nature is able to obtain high

• affinity carbohydrate ligands by displaying several monosaccharides/oligosaccharides on a protein scaffold or through a patch of lipids. This is known as the glycocluster effect or the multivalent presentation of sugar ligands [3][4]. This strategy can also be employed for the synthesis of carbohydrate

• mimetics, where several sugar ligands are attached to a non-natural scaffold. Glycopolymers where natural sugar ligands are presented along a synthetic polymer chain are an emerging class of carbohydrate mimetics [5]. Such glycopolymers offer great potential for various biotechnological and biomedical

Multivalent scaffolds induce galectin-3 aggregation into nanoparticles

• Candace K. Goodman,
• Mark L. Wolfenden,
• Pratima Nangia-Makker,
• Anna K. Michel,
• Avraham Raz and
• Mary J. Cloninger

Beilstein J. Org. Chem. 2014, 10, 1570–1577, doi:10.3762/bjoc.10.162

• protein:carbohydrate systems using a wide assortment of scaffolds and carbohydrates [2]. As research with multivalent glycosystems advances, one important target for potential therapy and understanding is the galectin family of proteins [3]. Members of the galectin family share a common conserved sequence carbohydrate

• , apoptosis, angiogenesis, and B cell activation [8][9][10]. Galectin-3 has been reported to be involved in mechanisms that cluster cell surface glycoproteins [10][11], cross-link receptors [12], and form lattices and larger aggregates [13]. Structurally, galectin-3 is composed of one carbohydrate recognition

• a series of carbohydrate-based ligands to galectin-3, which binds to lactose significantly better than to galactose or to N-acetylgalactosamine but does not bind to mannose [22][23][24]. Both the glycan ligand and the topological display on the cell surface are required for high affinity, selective

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

• detailed elucidation of carbohydrate–protein interactions and the discovery of more selective ligands. Heteromultivalent ligands, namely heteroglycoclusters (hGCs), represent ideal structures to achieve this purpose [5]. A few recent reports described the construction of various hGCs based on the

Synthesis and solvodynamic diameter measurements of closely related mannodendrimers for the study of multivalent carbohydrate–protein interactions

• Yoann M. Chabre,
• Alex Papadopoulos,
• Alexandre A. Arnold and
• René Roy

Beilstein J. Org. Chem. 2014, 10, 1524–1535, doi:10.3762/bjoc.10.157

• families of mannopyranoside-containing dendrimers for the purpose of studying subtle structural parameters involved in the measurements of multivalent carbohydrate–protein binding interactions. Toward this goal, two trimers 5 and 9, three 9-mers 12, 17, 21, and one 27-mer 23, varying by the number of atoms

• carbohydrate–protein interactions are at the forefront of a wide range of biological events which have triggered a plethora of versatile synthetic methods for the design of potent inhibitors and glycomimetics [1][2][3][4]. Among the diverse strategies leading to efficient ligands, glycopolymers [1][5][6][7

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

• (RCA120), the colloidal solution soon caused precipitations, while becoming colorless and transparent. In contrast, a solution of concanavalin A (Con A) caused no apparent change, indicating that the precipitation was caused specifically by carbohydrate–protein interactions. This notable phenomenon was

• ; 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

• Chemical Weapon Convention [4]. Ricin consists of a subunit A with ribonuclease activity and a subunit B possessing carbohydrate-binding domains specific to β-lactosyl linkage [5][6]. In the past years, the development of proteotoxin infection inhibitors based on carbohydrate molecules has attracted great

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

• of compounds, the carbohydrates. Carbohydrates are involved in numerous biological recognition processes, where they are often displayed in the form of multivalent conjugates such as on the surface of cells [1]. To investigate multivalency in carbohydrate recognition, multivalent glycomimetics, for

Multichromophoric sugar for fluorescence photoswitching

• Stéphane Maisonneuve,
• Rémi Métivier,
• Pei Yu,
• Keitaro Nakatani and
• Juan Xie

Beilstein J. Org. Chem. 2014, 10, 1471–1481, doi:10.3762/bjoc.10.151

• -functionalized moieties [18][19][20]. Monosaccharides can be readily functionalized with several propargyl groups to synthesize, using click chemistry, multivalent neoglycoconjugates for recognition studies with carbohydrate-binding proteins (lectins) [21][22][23][24] or to develop light-harvesting antenna

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

• polyethylene glycol (PEG), known as PEGylation, has been widely used to improve the bioavailability of proteins and low molecular weight drugs. The covalent conjugation of PEG to the carbohydrate moiety of a protein has been mainly used to enhance the pharmacokinetic properties of the attached protein while

• 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

• higher affinity for receptors as described for Shiga-like toxins [16] and other systems [17]. Several excellent reviews have been published on PEGylation of proteins, including PEG-drugs in the market [2][18][19][20][21]. However, PEGylation of carbohydrate molecules has been less exploited and studies

Biantennary oligoglycines and glyco-oligoglycines self-associating in aqueous medium

• Svetlana V. Tsygankova,
• Alexander A. Chinarev,
• Alexander B. Tuzikov,
• Nikolai Severin,
• Alexey A. Kalachev,
• Juergen P. Rabe,
• Alexandra S. Gambaryan and
• Nicolai V. Bovin

Beilstein J. Org. Chem. 2014, 10, 1372–1382, doi:10.3762/bjoc.10.140

• antennas, i.e., the number of glycine residues in a chain (n = 1–7) is different. Thirdly, the substances differ by the presence or absence of carbohydrate fragment (Sug), containing α-N-acetylneuraminic moiety (Neu5Acα). Diamines NH2–X–NH2 were the starting substances for the synthesis, oligoethylene

• aggregates in aqueous solution was about 1 μm (data not shown). The antiviral activity of biantennary glycopeptides was studied by means of a fetuin binding inhibition test (FBI-test) [17] (the glycoprotein fetuin contains several sialylated carbohydrate chains). In this test, the glycopeptides inhibited the

• about 100 Å. This distance value corresponds to the distance between the carbohydrate binding sites in one molecule of a hemagglutinin homotrimer and slightly exceeds the distance between a couple of hemagglutinin trimmers, which are closely situated on the virion surface. Experimental Reagents and

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

• wide range of physiological processes and the development of synthetic carbohydrate receptors (“synthetic lectins”) constitutes a key advance in biomedical technology. In this article we report a synthetic lectin that selectively binds to carbohydrates immobilized in a molecular monolayer. Inspired by

• β-D-galactose was observed by fluorescence microscopy. The selectivity and affinity of the synthetic lectin was screened in competition experiments. In addition, the carbohydrate binding of the synthetic lectin was compared with the carbohydrate binding of the lectins concanavalin A and peanut

• processes and offer an enormous potential to encrypt biological information [1][2][3][4]. In contrast to the linear nucleic acids and proteins, carbohydrates usually form branched oligomers or polymers which are joined together by a variety of linkages. The vast amount of resulting carbohydrate oligomers