Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• each year in predominately underdeveloped countries. The treatment of the disease is severely underdeveloped due to the ability of the Leishmania pathogen to evade and abate immune responses. In an effort to develop anti-leishmaniasis vaccines and adjuvants, novel carbohydrate-based probes were made to

• intracellular pathogens, such as Mycobacterium tuberculosis [10][11]. Carbohydrate-based probes provide one method to investigate parasitic mechanisms of immune suppression and evasion. The cell surface glycoconjugates on Leishmania have been implicated in the ability of the parasite to infect host cells, then

• , synthetic pathogen-associated carbohydrate probes are necessary to understand the LPG structure-to-function relationship. These synthetic oligosaccharides also provide a structurally homogeneous standard to study how these glycans interact with the host immune system in an effort to develop effective anti

Cyclopropene derivatives of aminosugars for metabolic glycoengineering

• Jessica Hassenrück and
• Valentin Wittmann

Beilstein J. Org. Chem. 2019, 15, 584–601, doi:10.3762/bjoc.15.54

• approach, cells are cultivated with an unnatural carbohydrate derivative carrying a chemical reporter group. After cellular uptake, the derivative is deacetylated, metabolized by the biosynthetic machinery and incorporated into glycoconjugates. The chemical reporter group can then be visualized using a

• bioorthogonal ligation reaction [5][6]. Mannosamine derivatives are of special interest because they are metabolized to sialic acids and then displayed as terminal structures on the cell surface [7]. Various carbohydrate derivatives with different reporter groups have been applied for MGE [2][3][4]. For example

• membrane glycoconjugates. However, many processes are responsible for the staining intensity of either intracellular or cell-surface proteins including cellular uptake of the carbohydrate derivative used for MGE, its metabolization, transport, speed of the ligation reaction, and the occurrence of

Olefin metathesis in multiblock copolymer synthesis

• Maria L. Gringolts,
• Yulia I. Denisova,
• Eugene Sh. Finkelshtein and
• Yaroslav V. Kudryavtsev

Beilstein J. Org. Chem. 2019, 15, 218–235, doi:10.3762/bjoc.15.21

• monomers to living polymer chains after full consumption of a previous monomer [48][49]. This technique was effectively applied for the synthesis of di-, tri- and tetrablock carbohydrate copolymers mediated by Schrock’ and Grubbs’ catalysts of the 1st (Gr1) and 2nd (Gr2) generations (Scheme 1, Figure 1

First synthesis of cryptands with sucrose scaffold

• Patrycja Sokołowska,
• Michał Kowalski and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2019, 15, 210–217, doi:10.3762/bjoc.15.20

• ]. There are also reports on the preparation of ‘distorted’ cyclodextrins in which diverse fragments are incorporated into the original oligosaccharide ring(s) [5]. Another class of sugar receptors is represented by macrocyclic derivatives with the carbohydrate unit being a part of a crown or aza-crown

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• substitution pattern of GlcA units for the efficient synthesis of CS oligomers. Keywords: carbohydrate chemistry; chondroitin sulfate; glycosylation; oligosaccharide synthesis; stereoselectivity; Introduction Chondroitin sulfate (CS) is a highly heterogeneous polysaccharide, constituted by the repetition of

• -O-pivaloylated building block. Pivaloyl groups are widely employed in carbohydrate chemistry and are especially indicated for the protection of 2-OH groups of glycosyl donors because they minimize the formation of orthoester byproducts. However, glycosylation experiments between monosaccharide units

Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• ). In this paper we review previous studies on the carbohydrate-binding characteristics of mycobacteria and related Mtb proteins, discussing their potential relevance to Mtb infection and pathogenesis. Keywords: adhesion; carbohydrates; fimbriae; lectins; Mycobacterium tuberculosis; pili; Introduction

• associated with intercellular binding, cell–cell recognition, intracellular protein trafficking, and toxin activity [26]. Lectins typically possess high carbohydrate ligand specificity, enabling precise control over protein–target contacts and associated downstream processes. Lectins are often easily

• identified based on the primary amino acid sequence alone, due to the presence of conserved lectin-associated domains (carbohydrate-recognition domains; CRDs) [27]. Well known lectin examples within the innate immune system include the DC-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC

Ruthenium-based olefin metathesis catalysts with monodentate unsymmetrical NHC ligands

• Veronica Paradiso,
• Chiara Costabile and
• Fabia Grisi

Beilstein J. Org. Chem. 2018, 14, 3122–3149, doi:10.3762/bjoc.14.292

• of highly performing NHC-based metathesis catalysts with N-alkyl groups, ruthenium benzylidene complexes containing carbohydrate-based NHCs derived from glucose (116) and galactose (117, Figure 21) were reported in 2009 [41]. These complexes were characterized in solution by NMR techniques which

• temperature 40 °C) compared to the benchmark catalysts GII-IMes and GII-SIMes, indicating that the steric bulk of the carbohydrate plays a role in influencing the geometry of the resulting olefinic product. Given the chiral nature of the carbohydrate attached to the NHC, complexes 116 and 117 were tested in

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• protected 3-aminoglycals from non-carbohydrate precursors. Most of them used a common methodology for the construction of the pyranosyl glycal ring which is based on a cycloisomerization reaction of chiral homopropargylic alcohols [7][8][9][10]. In some cases, the strategy used for the preparation of the

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• catalyst and carbohydrate or small polyethylene glycol (PEG) groups were attached [11]. As another strategy to modify a protein surface with olefin metathesis, Isarov and Pokorski introduced a Grubbs 3rd generation catalyst on the surface of lysozyme and performed ring-opening metathesis polymerization

Synthesis of α-D-GalpN₃-(1-3)-D-GalpN₃: α- and 3-O-selectivity using 3,4-diol acceptors

• Emil Glibstrup and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2018, 14, 2805–2811, doi:10.3762/bjoc.14.258

• ] has triggered the interest of carbohydrate chemists since the early days of complex oligosaccharides synthesis. The structure of the pentasaccharide part of the Forssman antigen was resolved in the seventies [3][4] and soon thereafter Paulsen and Bünsch finished the chemical synthesis of the

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• pathogen [10]. 3. Blocking adhesion and biofilm formation Bacterial adhesion to the host’s tissue is the initial step of every infection. In many cases, microbial adhesion is mediated by carbohydrate-binding proteins, so-called lectins, which recognize glycoconjugates on the surface of cells and tissue

• . Surface exposed glycoconjugates are highly abundant on all living cells and are generally referred to as the glycocalyx. Bacterial lectins act as adhesins with defined carbohydrate-binding specificities, in order to establish and maintain infection of the host’s various tissues and organs. Therefore, the

• ]. The crystal structure of FimH was published by Hultgren and Knight et al. in 1999 [14]. FimH is highly specific for α-D-mannoside ligands with this residue residing in a carbohydrate binding pocket with its α-linked substituent towards an adjacent cleft. This substituent, termed the aglycon, can also

Carbonylonium ions: the onium ions of the carbonyl group

• Daniel Blanco-Ania and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2018, 14, 2568–2571, doi:10.3762/bjoc.14.233

• ether (Scheme 1). One of the fields of Organic Chemistry more concerned on giving names to these intermediates has been carbohydrate chemistry. Its researchers have created different terms throughout history looking for a unique, concise and generic name for these kinds of intermediates found when

Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues

• Kai Zhang,
• Jiarong Li,
• Honglin Liu,
• Haiyou Wang and
• Lamusi A

Beilstein J. Org. Chem. 2018, 14, 2321–2330, doi:10.3762/bjoc.14.207

• . Particularly, the compound 8b was approximately as active as spinosad. Carbohydrate substituents are considered to be related closely to many secondary metabolites [19], hence, C17–O glycosyl analogues are regarded as efficient insecticides that are likely to rival present insecticides. However, as noted in

Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as inhibitors of GH38 α-mannosidases

• Maroš Bella,
• Sergej Šesták,
• Ján Moncoľ,
• Miroslav Koóš and
• Monika Poláková

Beilstein J. Org. Chem. 2018, 14, 2156–2162, doi:10.3762/bjoc.14.189

• ; inhibitors; pyrrolidines; synthesis; Introduction Carbohydrates as chiral templates for a construction of bioactive compounds are of steady interest in medicinal chemistry [1][2][3]. The polyfunctional nature of carbohydrate units offers many possibilities for the design of a wide variety of new compounds

• . Moreover, various desired substituents can be selectively appended to any required position of the carbohydrate unit. This leads to a preparation of mimetics that meet the requirements of metabolically more stable bioactive compounds. During the years, many scaffolds based on monosaccharides [4

• ], disaccharides or higher oligosaccharides [5][6] as well as multivalent [7][8] carbohydrate units have been developed. These glycomimetics and glycopeptides have also found applications as bioactive compounds [9][10]. One group of the scaffolds includes iminosugars [11][12] as analogues of the monosaccharides

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• nucleophile [13][14]. The design of new PHOX ligands is still subject to current research and the synthesis of a lot of different PHOX ligands have been reported during the last years [15][16][17][18]. Kunz reported the preparation of a carbohydrate based PHOX ligand 2 [19]. The starting material was D

• -glucosamine and the sugar was linked to the aromatic system via an annulated oxazoline. Palladium complexes of 2 were used in allylic substitution of allyl acetates with dimethyl malonate as nucleophile and ee values from 69% to 98% were obtained [19]. Recently, we presented the synthesis of carbohydrate

• ][22]. This led us to extend the concept of spiro-fused carbohydrate oxazolines for asymmetric synthesis by developing new types of carbohydrate-based PHOX ligands. Herein, we present ten novel spiro-PHOX ligands containing diphenylphosphino groups, 5, which can be synthesized in four to six steps

Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• comprising a lectin domain FimHL hosting the α-D-mannose-specific carbohydrate binding site and a pilin domain FimHP connecting the protein to the fimbrial shaft (Figure 2). Complexation of α-D-mannopyranoside ligands involves the entire mannoside glycon moiety whereas the aglycon portion sticks out of the

• mannosides 3–5 as photolabile ligands of FimH and evaluated their potential affinity by computer-aided docking. Docking studies Mannosides 3–5 (Figure 3) were docked into the FimH carbohydrate binding site using FlexX as implemented in Sybyl 6.9 [21][22][23]. Ligand structures were minimized using the Tripos

• carbohydrate binding site. They are flexible and can be more distant to one another (“open gate”) or closer together (“closed gate”) [20]. Both conformations were considered for the docking studies. For each docked conformation, a scoring value is obtained that correlates with the affinity of the ligand to the

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• reagents, mostly triphenylphosphine and a dialkyl azodicarboxylate. This reaction has been frequently used in carbohydrate chemistry for the modification of sugar hydroxy groups. Modification at the anomeric position, leading mainly to anomeric esters or glycosides, is of particular importance in the

• to the respective phosphine oxide and the azo reagent is reduced to the corresponding 1,2-hydrazinodicarboxylate (Scheme 1). As we have frequently utilized this valuable reaction in carbohydrate chemistry, in this account we have compiled literature, where the Mitsunobu reaction was used for the

• dimethylformamide, has been shown to be influential in terms of efficacy and stereoselectivity [19]. Since its infancy, the Mitsunobu reaction has found applications in carbohydrate chemistry, as its broad scope and mild conditions are ideal for the formation of conjugates with sensitive natural products. Standard

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• glycols, epoxides, and olefins takes place by the action of hypervalent iodine [38][71][72]. For example, Havare and Plattner reported the oxidative cleavage of α-aryl aldehydes using iodosylbenzene to give chain-shortened carbonyl compounds and formaldehyde [71]. In the field of carbohydrate chemistry

• towards oligosaccharides, which would also contribute to the identification and development of drug candidates. For example, cancer immunotherapy based on vaccines derived from carbohydrate antigen–adjuvant combinations has received much attention in recent years [75][76][77]. However, the difficulties

• associated with the isolation of tumor-associated carbohydrate antigens from natural sources have impeded extensive research. Thus, the most promising approach to the supply of these antigens is to develop a suitable method for their chemical synthesis. To date, various glycosylation reactions capable of

Synthetic avenues towards a tetrasaccharide related to Streptococcus pneumonia of serotype 6A

• Aritra Chaudhury,
• Mana Mohan Mukherjee and
• Rina Ghosh

Beilstein J. Org. Chem. 2018, 14, 1095–1102, doi:10.3762/bjoc.14.95

• ; oligosaccharides; stereoselectivity; total synthesis; Introduction Complex glycans serve as attractive targets for carbohydrate-based vaccines and therapeutics [1][2][3]. Streptococcus pneumonia (SPn) has been posing a serious threat in recent times. It is a major cause of pneumonia, bacteraemia, and meningitis

• most important causes of invasive pneumonococcal diseases [7]. These facts have led to extensive research towards the establishment of polysaccharide structures associated with the SPn serogroup 6 [8][9] (Figure 1). Initially, it was thought that due to their similar carbohydrate core structures the

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• synthesized in order to investigate the molecular basis of carbohydrate–minor groove DNA interactions by Vicent et al. [95]. NMR spectroscopy and molecular modeling studies further confirmed the existence of directional intramolecular hydrogen bonds and CH–π interactions, which results in stabilizing these

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• peracetylated D-IdoNAc 2c. Conclusion The presented synthetic route was successfully used to prepare both, D- and L-GalNAc, from non-carbohydrate starting materials over 9 steps with overall yields of 22% and 12%, respectively. Our approach combines the Sharpless epoxidation and Pd-catalyzed azide substitution

AuBr₃-catalyzed azidation of per-O-acetylated and per-O-benzoylated sugars

• Jayashree Rajput,
• Srinivas Hotha and
• Madhuri Vangala

Beilstein J. Org. Chem. 2018, 14, 682–687, doi:10.3762/bjoc.14.56

• applications and further demonstrates the value of gold catalysis in carbohydrate chemistry. Experimental General experimental methods: Chemicals and materials were obtained from commercial sources and used without further purification unless otherwise noted. 1H and 13C NMR spectra were recorded on a 400 MHz

Carbohydrate inhibitors of cholera toxin

• Vajinder Kumar and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2018, 14, 484–498, doi:10.3762/bjoc.14.34

• released by Vibrio cholera in the host’s intestine. The toxin enters intestinal epithelial cells after binding to specific carbohydrates on the cell surface. Over recent years, considerable effort has been invested in developing inhibitors of toxin adhesion that mimic the carbohydrate ligand, with

• particular emphasis on exploiting the multivalency of the toxin to enhance activity. In this review we introduce the structural features of the toxin that have guided the design of diverse inhibitors and summarise recent developments in the field. Keywords: carbohydrate; cholera; multivalency; toxin

• been drawn for the receptor binding to AB5 toxins; while some target on the individual binding sites, others are intended at designing multivalent ligands against the entire toxin B pentamer [6][30][31]. Monovalent receptor-binding inhibitors Bernardi and co-workers designed carbohydrate derivatives

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles

• Vivek Poonthiyil,
• Thisbe K. Lindhorst,
• Vladimir B. Golovko and
• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2

• many important biological processes, it is now well established that the binding interactions of a particular oligosaccharide, either with another carbohydrate or more commonly with carbohydrate-binding proteins (lectins), are generally weak. In order to augment these low affinity interactions

• , oligosaccharides usually bind lectins in a multivalent cooperative fashion. This avidity is significantly greater than the sum of the individual monomeric carbohydrate–protein interactions, and is sometimes referred to as the ‘cluster glycoside’ effect [6]. In order to study biological processes that involve these

• types of carbohydrate–protein interactions, it is therefore essential to present carbohydrates in a multivalent fashion. For that purpose, different scaffolds, such as peptides, proteins, lipids, and synthetic polymers, have all been used [7]. The search for better scaffolds for the presentation of