Synthesis of 1,2-cis-2-C-branched aryl-C-glucosides via desulfurization of carbohydrate based hemithioacetals

• Henok H. Kinfe,
• Fanuel M. Mebrahtu,
• Mandlenkosi M. Manana,
• Kagiso Madumo and
• Mokela S. Sokamisa

Beilstein J. Org. Chem. 2015, 11, 583–588, doi:10.3762/bjoc.11.64

• biologically important compounds. Although the synthesis of such carbohydrate derivatives is extensively studied, the synthesis of 1,2-cis-2-C-branched C-, S-, and N-glycosides is less explored. In this article a synthetic strategy for the synthesis of 1,2-cis-2-C-branched-aryl-C-glucosides is reported via a

• hydrogenolytic desulfurization of suitably orientated carbohydrate based hemithioacetals. 1,2-cis-2-Hydroxymethyl and 2-carbaldehyde of aryl-C-glucosides have been synthesized using the current strategy in very good yields. The 2-carbaldehyde-aryl-C-glucosides have been identified as suitable substrates for the

• stereospecific preparation of 2,3-unsaturated-aryl-C-glycosides (Ferrier products). Keywords: aryl-C-glucoside; desulfurization; Ferrier product; hemithioacetal; Introduction 1-C (C-glycosides) and 2-C-branched carbohydrates are important carbohydrate analogues which have found wide application in

Synthesis and biological evaluation of a novel MUC1 glycopeptide conjugate vaccine candidate comprising a 4’-deoxy-4’-fluoro-Thomsen–Friedenreich epitope

• Manuel Johannes,
• Maximilian Reindl,
• Bastian Gerlitzki,
• Edgar Schmitt and
• Anja Hoffmann-Röder

Beilstein J. Org. Chem. 2015, 11, 155–161, doi:10.3762/bjoc.11.15

• cells from healthy ones by means of tumor-associated antigens (TACA), e.g., partial structures of the mucin glycoprotein MUC1 [6][7]. Cancer-associated MUC1 is characterized by the presence of specifically altered carbohydrate side chains in its extracellular tandem-repeat domain due to fundamental

• , which becomes accessible to the immune system and can be used as an additional immunogenic determinant for carbohydrate-based cancer vaccines [13]. Despite encouraging results with two- and three-component MUC1 conjugate vaccines in mice models [14][15][16][17][18][19][20][21][22][23][24][25], immune

• tolerance to carbohydrate antigens remains a major obstacle in initiating an effective and long-lasting immune protection against malignancies. One strategy to enhance the immunogenicity of carbohydrate antigens relies upon modification of the glycan hapten [26][27], which renders it more foreign to the

A carbohydrate approach for the formal total synthesis of (−)-aspergillide C

• Pabbaraja Srihari,
• Namballa Hari Krishna,
• Ydhyam Sridhar and
• Ahmed Kamal

Beilstein J. Org. Chem. 2014, 10, 3122–3126, doi:10.3762/bjoc.10.329

Synthesis and characterization of pH responsive D-glucosamine based molecular gelators

• Navneet Goyal,
• Hari P. R. Mangunuru,
• Bargav Parikh,
• Sonu Shrestha and
• Guijun Wang

Beilstein J. Org. Chem. 2014, 10, 3111–3121, doi:10.3762/bjoc.10.328

• ]. Several pH responsive small molecular gelators have been designed and synthesized and have shown a variety of potential applications [29][30][31][32][33][34]. Among the different classes of LMWGs, carbohydrate-based systems are especially interesting due to their potential applications in biomedical

A general metal-free approach for the stereoselective synthesis of C-glycals from unactivated alkynes

• Shekaraiah Devari,
• Manjeet Kumar,
• Ramesh Deshidi,
• Masood Rizvi and
• Bhahwal Ali Shah

Beilstein J. Org. Chem. 2014, 10, 2649–2653, doi:10.3762/bjoc.10.277

• single step from a variety of acetylenes , i.e., arylacetylenes and most importantly aliphatic alkynes. Keywords: α-selective; C-alkynylation; glycal; metal free; TMSOTf; Introduction C-Glycosides represent an important class of carbohydrate mimics, owing to their presence in a large number of

• particular interest as it is amenable to further modifications into chiral molecules, carbohydrate analogues, and natural products, such as tautomycin [17][18] and ciguatoxin [19][20][21]. In recent past, significant efforts have been directed toward the C-alkynylation of glycals [9][22][23]. However, all

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

• Yiyang Liu,
• Marc Liniger,
• Ryan M. McFadden,
• Jenny L. Roizen,
• Jacquie Malette,
• Corey M. Reeves,
• Douglas C. Behenna,
• Masaki Seto,
• Jimin Kim,
• Justin T. Mohr,
• Scott C. Virgil and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2014, 10, 2501–2512, doi:10.3762/bjoc.10.261

• . This publication highlights recent methods for setting quaternary and tetrasubstituted tertiary carbon stereocenters to address the synthetic hurdles encountered over many decades across multiple compound classes spanning carbohydrate derivatives, terpenes, and alkaloids. These enantioselective methods

Synthesis of aromatic glycoconjugates. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger and
• Thomas Ziegler

Beilstein J. Org. Chem. 2014, 10, 2453–2460, doi:10.3762/bjoc.10.256

• difficult despite the great achievements in this field during the past decades. Therefore, the application of oligosaccharide mimetics which may be synthesized more easily in larger amounts appears to be a useful tool to investigate, for instance, specific carbohydrate–protein or carbohydrate–carbohydrate

• interactions. Recently our group has prepared a series of trifunctional glycopeptide building blocks with aliphatic backbones, which allow for the automated construction of combinatorial libraries of highly divers glycopeptides suitable for studying carbohydrate–protein interactions [5][6][7][8]. Hitherto, our

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