Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• -monotosylated α-, β-, and γ-CDs [94]. The further reaction of the prepared compounds resulted in a CD derived cyclic oligosaccharide, which contained one mannose residue, in the form of 2,3-mannoepoxide. Type 3) reactions in the further derivatization of regioselectively activated – by sulfonic esters or

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

Exploring architectures displaying multimeric presentations of a trihydroxypiperidine iminosugar

• Camilla Matassini,
• Stefania Mirabella,
• Andrea Goti,
• Inmaculada Robina,
• Antonio J. Moreno-Vargas and
• Francesca Cardona

Beilstein J. Org. Chem. 2015, 11, 2631–2640, doi:10.3762/bjoc.11.282

• strategy for the synthesis of diversely functionalized trihydroxypiperidines through double reductive amination of the D-mannose-derived aldehyde 2 (Scheme 1) [24][25]. Among the 1-azasugars accessed with this methodology, our attention was drawn to the enantiomer of natural 3,4,5-trihydroxypiperidine (1

• ] with two different dendrimeric alkyne scaffolds. Results and Discussion The “masked” dialdehyde intermediate 2 was easily synthesized in four steps and 80% overall yield from D-mannose without the need of any chromatographic purification, by following a slight modification of the published procedure

Towards inhibitors of glycosyltransferases: A novel approach to the synthesis of 3-acetamido-3-deoxy-D-psicofuranose derivatives

• Maroš Bella,
• Miroslav Koóš and
• Chun-Hung Lin

Beilstein J. Org. Chem. 2015, 11, 1547–1552, doi:10.3762/bjoc.11.170

• transformation of D-mannose, is described. In addition, the thioglycosylation of fully protected 3-acetamido-3-deoxy-D-psicofuranose 11 with ethanethiol was examined under various conditions. Results and Discussion The synthesis of the saccharide moiety of potential GnTs inhibitors started from commercially

• available D-mannose. The latter was transformed into suitably protected 1,2:4,5-di-O-isopropylidene-6-O-pivaloyl-D-mannitol (1) in three steps by the procedures described in the literature [20][21][22]. The standard preparation of mesylate with methanesulfonyl chloride and Et3N as base smoothly provided 1,2

Are D-manno-configured Amadori products ligands of the bacterial lectin FimH?

• Tobias-Elias Gloe,
• Insa Stamer,
• Cornelia Hojnik,
• Tanja M. Wrodnigg and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2015, 11, 1096–1104, doi:10.3762/bjoc.11.123

• easily obtained by a Grignard reaction of 2,3:5,6-di-O-isopropylidene-D-mannose employing commercially available vinylmagnesium bromide (Scheme 2) [16][17]. This C-elongation approach leads to a mixture of C-2 diastereomers, however, during the Amadori rearrangement this centre is converted to a keto

• ligation method for conjugation of unprotected sugars and amines, when applied to suitable sugar substrates. Herein, we evaluated this synthetic method for the preparation of ligands for the α-D-mannose-specific type 1-fimbrial bacterial lectin FimH. The synthesis of heptopyranose 8 as a starting material

Glycodendrimers: tools to explore multivalent galectin-1 interactions

• Jonathan M. Cousin and
• Mary J. Cloninger

Beilstein J. Org. Chem. 2015, 11, 739–747, doi:10.3762/bjoc.11.84

• sixth generation dendrimer, indicating that binding requires more than merely an array of hydrogen bonds. Small nanoparticles (340 ± 20 nm) were obtained when mannose functionalized G(6)-PAMAMs were combined with galectin-1, and neither monomeric lactose nor monomeric mannose inhibited the formation of

• these aggregates. This indicates that nanoparticles formed using the mannose-functionalized dendrimer do not rely on interactions in the β-galactoside binding site on galectin-1 and that non-specific glycodendrimer/galectin-1 interactions are responsible for the formation of these small aggregates

• aggregation is 6 mM. On a per lactose basis, this concentration is 15-fold higher than the 66 µM concentration of 1 that was required for complete inhibition of cellular aggregation. Additionally, mannose-functionalized G(6)-PAMAM dendrimers did not inhibit cellular aggregation. Discussion The results of the

Probing multivalency in ligand–receptor-mediated adhesion of soft, biomimetic interfaces

• Stephan Schmidt,
• Hanqing Wang,
• Daniel Pussak,
• Simone Mosca and
• Laura Hartmann

Beilstein J. Org. Chem. 2015, 11, 720–729, doi:10.3762/bjoc.11.82

• protein receptors are formed to control cell–cell recognition, cell adhesion and related processes. The aim of this work is to shed light on the principles of complex formation between surface anchored carbohydrates and receptor surfaces by measuring the specific adhesion between surface bound mannose on

• density variation of functional groups on the PEG scaffold using unsaturated carboxylic acids (crotonic acid, acrylic acid, methacrylic acid) as grafting units for mannose conjugation. We showed by a range of analytic techniques (ATR–FTIR, Raman microscopy, zeta potential and titration) that this

• synthetic strategy allows for straightforward variation in grafting density and grafting length enabling the controlled presentation of mannose units on the PEG network. Finally we determined the specific adhesion of PEG-network-conjugated mannose units on ConA surfaces as a function of density and grafting

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• high mannose epitope of gp120. For this purpose, the aptamer library was functionalized with oligomannoses (Man4-azide or Man9-azide) leading to the selection of glycan-functionalized aptamers bearing 7–14 glycan units and with a KD below 220 nM. A mutagenesis study showed that the affinity was also

• ligands in order to recapitulate the geometry of HIV’s gp120 glycan epitope which is composed of multiple copies of a high mannose undecasaccharide [38]. An advantage of displaying ligands through template assembly of discrete units is that the pairing and distance can be controlled though the template

• instructions. To this end a pilot library of fourteen PNA-tagged glycoconjugates that included mannose disaccharides joined by linkers of different lengths were paired through hybridization, varying the ligand combinations and interligand distances. Measuring the affinity of 32 different assemblies against

Synthesis of carbohydrate-scaffolded thymine glycoconjugates to organize multivalency

• Anna K. Ciuk and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2015, 11, 668–674, doi:10.3762/bjoc.11.75

• Discussion For the conjugation of two thymine and eventually two glycothymine branches on a glycosidic scaffold, the 2- and 3-hydroxy functions of mannose were chosen. These two functional groups can be easily addressed orthogonally to the rest of the molecule. In addition, the vicinal 2- and 3-hydroxy

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

• –17; experimental procedures for ITC and biofilm inhibition studies, and for the synthesis of tris propargyl precursor 2, protected clusters 9–12, and 6-C-mannose cluster 15; additional DLS and ITC spectra, additional biofilm quantification information. Supporting Information File 604: Experimental

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

• synthesized containing up to two azobenzene units in the oligomeric backbone and presenting galactose residues in the side chains. As control structures, glycooligomers containing either a hydrophilic flexible linker unit instead of the azobenzene moiety, or mannose instead of galactose ligands were

• -galactose-polymer and α-D-mannose-polymer as negative control (see Supporting Information File 1). In a first experiment, binding of PA-IL (1 µM) to the chip was determined and set as 100%. In a second set of experiments, binding of preincubated mixtures of PA-IL (1 µM) and glycooligomers at serial

• % binding (IC50) was derived for the different glycooligomers (Table 2). All galactose-containing glycooligomers can bind to PA-IL. The mannose-containing control oligomer does not show any binding. This confirms that the backbone itself does not undergo non-specific interactions with the receptor, as we

The search for new amphiphiles: synthesis of a modular, high-throughput library

• George C. Feast,
• Thomas Lepitre,
• Xavier Mulet,
• Charlotte E. Conn,
• Oliver E. Hutt,
• G. Paul Savage and
• Calum J. Drummond

Beilstein J. Org. Chem. 2014, 10, 1578–1588, doi:10.3762/bjoc.10.163

• organic amphiphilic compounds was synthesised consisting of glucose, galactose, lactose, xylose and mannose head groups and double and triple-chain hydrophobic tails. A modular, high-throughput approach was developed, whereby head and tail components were conjugated using the copper-catalysed azide–alkyne

• would provide a wealth of data on the appropriate characteristics for a self-assembled sugar-based amphiphilic drug. Five sugars were chosen for this library: glucose, galactose, lactose, xylose and mannose. Glucose and galactose amphiphiles have been demonstrated to possess slightly different lyotropic

• associated with these sugars are linked through a β-anomeric linkage, therefore an α-linked mannose was also selected for comparison (Figure 3). These azido-sugars were commercially available with the exception of azido-xylose 27, which was synthesised in three steps from the parent sugar using

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

• 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

• series of control experiments indicate that aggregation is induced by the binding of galectin-3 to lactose on the dendrimers. No observable particles were detected upon addition of a mannose-functionalized G(4) dendrimer (Table S3 in Supporting Information File 1). Pre-incubation of galectin-3 with 1 mM

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

• processes. Recently, it was synthetized a diaminopyrrolic tripodal receptor that is selective for mannosides, which are obtained from mannose, a sugar with significant relevance in living systems. However, this receptor is significantly more active in acetonitrile than in water. In this work, we performed

• : conformational analysis; constant-pH MD; mannose; multivalent glycosystems; pH; synthetic receptor; Introduction The recognition of specific carbohydrates is an important step in several biological processes [1]. To better understand these recognition processes, several synthetic receptors have been developed

• over the years [1][2][3][4][5][6]. Most of these were developed for glucose since it is one of the most common sugars in living systems [7] and the preferred monosaccharide for energy storage [8]. However, mannose is essential for various biological functions, such as molecular recognition, being one

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

• notable biological and physical properties. For example, bis(α-D-mannopyranosyl)-[60]fullerene is capable of forming a liposome-like supramolecule in aqueous media and exhibits a strong binding activity to an α-mannose-binding lectin (concanavalin A, Con A) as the result not only of carbohydrate cluster

• , precipitation tests were conducted with Ricinus communis agglutinin (RCA120) [27], ricin and concanavalin A (Con A) [28]. RCA120 is a ricin-like lectin and able to bind β-galactose residues. Con A is an α-mannose-specific lectin. When RCA120 (10 μL, 20 μg mL−1) was added to this suspension (0.1 mL, 300 μM), the

Efficient routes toward the synthesis of the D-rhamno-trisaccharide related to the A-band polysaccharide of Pseudomonas aeruginosa

• Aritra Chaudhury,
• Sajal K. Maity and
• Rina Ghosh

Beilstein J. Org. Chem. 2014, 10, 1488–1494, doi:10.3762/bjoc.10.153

• candidates. Thus, we targeted the trisaccharide [α-D-Rhap-(1→3)-α-D-Rhap-(1→3)-α-D-Rhap] as our synthetic goal toward construction of a probable vaccine candidate against P. aeruginosa. The synthesis of the D-rhamnose-based oligosaccharide from the D-mannose motif has received substantial attention over the

• which are rather expensive. Moreover, additional steps are required for the preparation of these adequately derivatized mannose-based systems from which the D-rhamnose motif may be accessed. Other reports on the D-rhamnose-based synthesis have also surfaced in recent times [24][25]. Apart from this, the

• requires four steps for the conversion of D-mannose to D-rhamnose on which further manipulations are required to reach the adequately designed derivatives. This makes the starting material preparations rather long drawn. Keeping these limitations in mind we selected the protocol devised by Pedersen et al

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

• ]. Mannose was also PEGylated in order to target drugs specifically to mannose receptors present in liver endothelial cells. Mannosyl PEGylated polyethylenimine (PEI) conjugates were synthesized either by direct coupling the mannose and the PEG chain to the PEI backbone (Figure 3A) or by attaching the

• mannose to PEI via a PEG chain spacer (Figure 3B). This system was used to deliver small interfering RNA (siRNA) into a murine macrophage cell line [44]. Mannose residues as their 2-aminoethyl glycosides were attached by reductive amination to the surface of copolymer micelles of PEG with poly-ε

• -caprolactone for targeting dendritic cells and macrophages (Figure 4) [45] Both mannose and galactose were attached to PEGylated nanoparticles by click-chemistry between their propargyl glycosides and a gold nanoparticles derivatized with an azide-functionalized PEG [46]. Also, several unprotected carbohydrate

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

• our previous work, we prepared a fluorescently labeled synthetic lectin consisting of a cyclic dimer of the tripeptide Cys-His-Cys, which forms spontaneously by air oxidation of the monomer. Amine-tethered derivatives of N-acetylneuraminic acid (NANA), β-D-galactose, β-D-glucose and α-D-mannose were

• HisHis towards immobilized NANA in comparison with the glycosides of glucose (Glc), galactose (Gal) and mannose (Man) (Figure 1). In this study, we exploit the epoxide ring opening reaction of amine-tethered carbohydrates on epoxide-terminated SAMs [42] to print carbohydrate microarrays on silicon and

• function was introduced on the terminus of the spacer in order to ensure reaction with the epoxide-functionalized substrate upon µCP. The NANA ink was prepared by solution phase peptide coupling using the DIPCDI/Oxyma pure® coupling protocol. The glucose (Glc), galactose (Gal) and mannose (Man) inks were

Human dendritic cell activation induced by a permannosylated dendron containing an antigenic GM₃-lactone mimetic

• Renato Ribeiro-Viana,
• Elena Bonechi,
• Javier Rojo,
• Clara Ballerini,
• Giuseppina Comito,
• Barbara Richichi and
• Cristina Nativi

Beilstein J. Org. Chem. 2014, 10, 1317–1324, doi:10.3762/bjoc.10.133

• residues of mannose for DC targeting and one residue of an immunogenic mimetic of a carbohydrate melanoma associated antigen. The immunological assays demonstrated that the glycodendron 5 is able to induce human immature DC activation in terms of a phenotype expression of co-stimulatory molecules

• , dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN), which belongs to the class of CLRs, is expressed mainly on the surface of immature DCs and plays a crucial role in the uptake of specific pathogens. DC-SIGN is able to bind in a Ca2+-dependent manner mannose and fucose residues on highly

• biological properties of the monovalent synthetic antigen as an immunomodulator as well as an anti-adhesive agent in melanoma progression. Taking into account all these data and relying on recent results on the use of mannose-based glycodendrons as vectors for antigen delivery to DCs [34], we report here on

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

Biosynthesis of rare hexoses using microorganisms and related enzymes

• Zijie Li,
• Yahui Gao,
• Hideki Nakanishi,
• Xiaodong Gao and
• Li Cai

Beilstein J. Org. Chem. 2013, 9, 2434–2445, doi:10.3762/bjoc.9.281

• synthesis of L-fructose using L-mannose as a substrate through aldo–keto isomerization (Scheme 8) [59]. Dhawale et al. demonstrated another route via bacterial oxidation of L-mannitol (Scheme 8) [42]. Interestingly, the previously mentioned versatile DTEase from Pseudomonas sp. ST-24 could also catalyze the

• signaling, immunological recognition and host–pathogen interactions [63][64]. Gullapalli et al. demonstrated an effective way of obtaining deoxy L-fructose by combining chemical and biotechnological approaches (Scheme 10) [8]. Hydrogenation of 6-deoxy-L-mannose (L-rhamnose) produced 6-deoxy-L-mannitol (L

• engineered Corynebacterium glutamicum was used to produce guanosine-5’-diphosphate (GDP)-L-fucose, the precursor of fucosyl-oligosaccharides, from glucose and mannose [95]. L-Fucose (or its analogs) can also be prepared in vitro enzymatically in a three-step procedure (Scheme 16) [96]. Firstly, L-fuculose-1

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

• disaccharide 17 and anhydro sugar 5 (Scheme 5). In trisaccharide 25, three anomeric protons were noticed at δ 4.88 (d, J = 1.6 Hz, 1H), 4.91 (d, J = 1.6 Hz, 1H), 5.61 (dd, J = 1.6, 3.2 Hz, 1H) ppm. The 13C NMR spectrum revealed that there are three mannose residues with 1,2-trans configuration as their

• considered to be more reactive than the glycosyl donors without axial hydroxy group. For example, β-D-glucose is less reactive than α-D-glucose or α-D-mannose. In order to verify the effect of the differences in reactivity on the cleavage of the interglycosidic bond, armed disaccharide 26 was prepared and

Flow synthesis of a versatile fructosamine mimic and quenching studies of a fructose transport probe

• Matthew B. Plutschack,
• D. Tyler McQuade,
• Giulio Valenti and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 2022–2027, doi:10.3762/bjoc.9.238

• the synthesis of 1-amino-2,5-anhydro-D-mannose (“mannitolamine”), a key intermediate to the 7-nitro-1,2,3-benzadiazole conjugate (NBDM), using commercially available fluidic devices to increase the throughput. The approach is the first example of a flow-based Tiffeneau–Demjanov rearrangement

• . Continuous flow synthesis of the key intermediate 1-amino-2,5-anhydro-D-mannose (3). Batch versus flow comparison. Supporting Information Supporting Information File 482: Experimental part. Acknowledgements Financial support from the Max Planck Society and the National Science Foundation (USA; CHE-1152020

Appel-reagent-mediated transformation of glycosyl hemiacetal derivatives into thioglycosides and glycosyl thiols

• Tamashree Ghosh,
• Abhishek Santra and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 974–982, doi:10.3762/bjoc.9.112

• formation of β-glycosyl thiols. In the case of D-mannose and L-rhamnose, exclusive formation of β-products were unambiguously confirmed from the coupling constant at the anomeric center (JC-1,H-1) in the gated 1H coupled 13C NMR spectra. Coupling constant (JC-1,H-1) = 143 Hz and 142 Hz (less than 160 Hz) in

Synthesis and testing of the first azobenzene mannobioside as photoswitchable ligand for the bacterial lectin FimH

• Vijayanand Chandrasekaran,
• Katharina Kolbe,
• Femke Beiroth and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2013, 9, 223–233, doi:10.3762/bjoc.9.26

• more stable (E)-form. Biological testing of azobenzene mannobioside 2 As a test system for mannose-specific bacterial adhesion, fluorescent GFP-transfected E. coli bacteria (pPKL1162) [23] were employed and tested on a mannan-coated polystyrene microtiter plate surface. In this setup the amount of

• solution of (E)-2 was serially diluted, in the second case, this stock solution of (E)-2 was irradiated for 15 minutes to obtain the pure (Z)-2 isomer for subsequent serial dilution. The effect of both isomers as inhibitors of mannose-specific bacterial adhesion was then measured in a concentration

• almost quantitative and the resulting (Z)-isomer is especially long-lived. Both isomers are very well water-soluble and could be independently tested as inhibitors of mannose-specific bacterial adhesion and showed an equal and high inhibitory potency in the range of the well-known high-affinity inhibitor