Tools for generating and analyzing glycan microarray data

• Akul Y. Mehta,
• Jamie Heimburg-Molinaro and
• Richard D. Cummings

Beilstein J. Org. Chem. 2020, 16, 2260–2271, doi:10.3762/bjoc.16.187

• monosaccharide and linkages, and assigns each node weights depending on their binding to the ligand [49]. MCAW-DB offers a unique perspective to glycan array binding results and even takes into account gaps in structures. The tool has parameters (such as weighting) which may need to be optimized to work with

GlypNirO: An automated workflow for quantitative N- and O-linked glycoproteomic data analysis

• Toan K. Phung,
• Cassandra L. Pegg and
• Benjamin L. Schulz

Beilstein J. Org. Chem. 2020, 16, 2127–2135, doi:10.3762/bjoc.16.180

• glycopeptides based on peptide sequence and glycan monosaccharide composition is comparatively reliable with modern LC–MS/MS and data analytics, it is much more difficult to unambiguously assign the precise site of modification within a glycopeptide. GlypNirO therefore provides two options for analysis: site

• NHFAGNa and Modification Type(s) column, the script obtained the monosaccharide composition of the attached glycan. In the standard Byonic output, only the ∆ mass of the modification is directly indicated on the modified peptide sequence, with no direct indication of the identity of the corresponding

• unmodified peptide sequence, glycan monosaccharide composition, calculated m/z, and site of glycosylation were grouped. For each group, the PSM precursor m/z value with the highest associated Area was selected as the unique PSM. The Area associated with each unique PSM was used for the calculation of the

How and why plants and human N-glycans are different: Insight from molecular dynamics into the “glycoblocks” architecture of complex carbohydrates

• Carl A. Fogarty,
• Aoife M. Harbison,
• Amy R. Dugdale and
• Elisa Fadda

Beilstein J. Org. Chem. 2020, 16, 2046–2056, doi:10.3762/bjoc.16.171

• of the N-glycan and its structural dynamics, therefore its selective recognition by lectin receptors and antibodies. The atomistic-level of detail information that the MD simulations provide us with, highlights that the effects of different functionalizations, in terms of monosaccharide types and

• linkages, are primarily local, affecting the immediate spatial vicinity of the monosaccharide within the N-glycan structure. Within this framework, we propose an alternative approach that can help to describe and predict the architecture of N-glycans based on the combination of structural 3D units, or

• glycoblocks. Unlike a description based on the monosaccharide sequence and linkages as two separate features, the transition to well-defined and self-contained units, integrating information on both monosaccharides and linkages, can help us rationalize and deconvolute the glycans structural disorder and

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• ][8][9]. Various lipid A derivatives have since been synthesized to dissociate endotoxic effects from beneficial immunomodulatory activities. Lipid X, 2-N;3-O-di[(R)-3-hydroxytetradecanoyl]-ᴅ-glucosamine-1-phosphate, is the naturally occurring early monosaccharide precursor of lipid A biosynthesis

• -phenyltrifluoroacetimidate glycosyl donor 20 by reaction with 2,2,2-trifluoro-N-phenylacetimidoyl chloride in the presence of base DBU [14]. The monoacylated derivative 15 is also the key building block for the synthesis of lipid X monosaccharide 1 (Scheme 3). After the N-Troc protecting group was removed as described above

• catalytic hydrogenolysis over Pd/C under 15 kg/cm2 of H2 to give the target lipid X monosaccharide 1 (as triethylammonium salt) in good yield. Having the glycosyl donor 20 and acceptor 18 at hand (Scheme 2), in order to prepare the disaccharide precursor, the glycosylation reaction was performed first

Synthesis of the tetrasaccharide repeating unit of the O-specific polysaccharide of Azospirillum doebereinerae type strain GSF71^T using linear and one-pot iterative glycosylations

• Arin Gucchait,
• Pradip Shit and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2020, 16, 1700–1705, doi:10.3762/bjoc.16.141

• glycosylation in one pot was developed and is reported herein. Results and Discussion At the beginning, the retrosynthetic analysis suggested that a sequential glycosylation reaction using judiciously protected monosaccharide thioglycosides could be the best strategy for achieving the desired tetrasaccharide 1

• . Accordingly, differentially protected monosaccharide intermediates such as ᴅ-glucosamine derivative 2 [22], ʟ-rhamnose derivatives 3 [23], and 4 [24] were prepared following the literature reported reaction conditions. The selection of the p-methoxybenzyl (PMB) group for the temporary protection of the chain

Synthesis of Streptococcus pneumoniae serotype 9V oligosaccharide antigens

• Sharavathi G. Parameswarappa,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2020, 16, 1693–1699, doi:10.3762/bjoc.16.140

• reducing-end monosaccharide 14 equipped with the linker in 70% yield as a mixture of anomers (α:β = 2:1) (Scheme 2). The reductive opening of the benzylidene protecting group in 14 enabled the separation of anomers and furnished acceptor 15α [28], that was reacted with thioglucoside 11 to yield exclusively

Convenient synthesis of the pentasaccharide repeating unit corresponding to the cell wall O-antigen of Escherichia albertii O4

• Tapasi Manna,
• Arin Gucchait and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2020, 16, 106–110, doi:10.3762/bjoc.16.12

• of pentasaccharide 1 was achieved using a convergent as well as a block synthetic strategy. For this purpose, a series of suitably functionalized monosaccharide intermediates 2 [20], 3 [21], 4 [22], 5 [23], 6 [24] and 7 [25] were prepared from the commercially available reducing sugars utilizing the

• reaction conditions reported in the literature (Figure 1). Although the monosaccharide intermediates used for the construction of the pentasaccharide derivative 15 are known in the literature, preparation of these intermediates required multiple step reaction sequences. Having obtained the monosaccharide

SnCl₄-catalyzed solvent-free acetolysis of 2,7-anhydrosialic acid derivatives

• Kesatebrhan Haile Asressu and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2019, 15, 2990–2999, doi:10.3762/bjoc.15.295

• ]. N-Acetylneuraminic acid (Neu5Ac) is the most studied monosaccharide from the 50 derivatives of sialic acid that are found in nature. The most common glycosidic linkages of Neu5Ac in glycoconjugates are α(2→3) and α(2→6) to galactose, α(2→8) and α(2→9) in polysialic acids [2][3], fucosyl and

• Lewis acid type and amount (both catalytic and stoichiometric), solvent, acetolysis agent, reaction time, and temperature. However, these conditions were unsuccessful using 2,7-anhydro-based monosaccharide derivatives bearing NHAc, NAc2, and NAcBz functionalities and the disaccharides containing a 2,7

• -anhydro-Neu5N3 unit. Meanwhile, we successfully developed a convenient route to conduct the SnCl4-catalyzed acetolysis of 2,7-anhydro-Neu5N3 monosaccharide derivatives functionalized with a variety of protecting groups. The acetolysis products could further be transformed into regioselectively protected

Automated glycan assembly of arabinomannan oligosaccharides from Mycobacterium tuberculosis

• Alonso Pardo-Vargas,
• Priya Bharate,
• Martina Delbianco and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2019, 15, 2936–2940, doi:10.3762/bjoc.15.288

• -(1,6)-Man, α-(1,5)-Ara, and α-(1,2)-Man was synthesized by AGA using three monosaccharide building blocks. The linear oligomannosides were readily assembled and isolated in short time and high yield under standard conditions. The introduction of a capping step after each glycosylation and optimized

Influence of the cis/trans configuration on the supramolecular aggregation of aryltriazoles

• Sara Tejera,
• Giada Caniglia,
• Rosa L. Dorta,
• Andrea Favero,
• Javier González-Platas and
• Jesús T. Vázquez

Beilstein J. Org. Chem. 2019, 15, 2881–2888, doi:10.3762/bjoc.15.282

• , and also that they occured between specific phenyltriazoles. Specifically, these interactions formed between the phenyltriazole moieties in position 1 of a monosaccharide (A) and the phenyltriazole functions in position 1 of its vicinal monosaccharide (B, Figure 5, red lines). Similarly, the

• phenyltriazole substituents in position 2 of this monosaccharide (B) interacted with a corresponding phenyltriazole in position 2 of the vicinal monosaccharide (C, Figure 5, green lines). In addition, it is worth mentioning the presence of a number of DMSO solvate molecules in the crystal packing next to the

Chemical synthesis of the pentasaccharide repeating unit of the O-specific polysaccharide from Escherichia coli O132 in the form of its 2-aminoethyl glycoside

• Debasish Pal and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2019, 15, 2563–2568, doi:10.3762/bjoc.15.249

• + 2] strategy where the required monosaccharide building blocks are prepared from commercially available sugars through rational protecting group manipulation. The NIS-mediated activation of thioglycosides was used extensively for the glycosylation reactions throughout. Keywords: 2-aminoethyl

• the aforementioned target. Therefore, the first disconnection gave the trisaccharide acceptor 11 and the disaccharide donor 16. Further disconnection on the trisaccharide 11 gave disaccharide 5 and the monosaccharide 9. Disaccharide 5 is accessible from monosaccharide acceptor 2 and donor 3. Similarly

• , the disaccharide donor 16 may be prepared from monosaccharide acceptor 15 and donor 14. The monosaccharide building blocks can be prepared from commercially available ᴅ-glucose, ᴅ-galactose, ᴅ-glucosamine hydrochloride and ʟ-rhamnose through rational protecting group manipulations (Figure 2

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• existence of water pockets/bridges between the monosaccharide residue and peptide backbone, hence maintaining the defined conformation. Structural investigation of the glycopeptides Although the temperature factor gives important structural information, the most valuable and crucial data were obtained from

• (see Table 3) allowed only to conclude that peptide 4 did not adopt the often observed polyproline type helix [38] nor the extended conformation postulated by Corzana et al. [33]. Interestingly, also the arrangement of the monosaccharide moiety is much more ordered in glycopeptide 4 in comparison to

• of monosaccharide moiety. A) cluster 1 for glycopeptide 3, B) cluster 1 for glycopeptide 4. A) Modification of Fmoc-Sieber-PS resin: a. piperidine in DMF (20% v/v), rt; 3 × 10 min; b. o-NBS-Cl (4 equiv), collidine (10 equiv) NMP, rt, 2 h, twice; c. triphenylphosphine (PPh3, 5 equiv), methanol (MeOH

Anomeric sugar boronic acid analogues as potential agents for boron neutron capture therapy

• Daniela Imperio,
• Erika Del Grosso,
• Silvia Fallarini,
• Grazia Lombardi and
• Luigi Panza

Beilstein J. Org. Chem. 2019, 15, 1355–1359, doi:10.3762/bjoc.15.135

• and biological behavior of novel derivatives containing this functional group at the anomeric position, giving rise to an isostere analogue able to mimic the monosaccharide (see Figure 1). Results and Discussion In the present paper the synthesis of two analogues bearing a boron atom at the anomeric

Molecular recognition using tetralactam macrocycles with parallel aromatic sidewalls

• Dong-Hao Li and
• Bradley D. Smith

Beilstein J. Org. Chem. 2019, 15, 1086–1095, doi:10.3762/bjoc.15.105

• interactions and higher monosaccharide affinities. In addition, there was a remarkable improvement in affinity for larger oligosaccharides, presumably due to a stronger hydrophobic effect elicited by the extended hydrophobic surface of the tetralactam sidewalls. The Davis work has also uncovered a binding

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• to attenuate such processes [3][10][11][14]. Experimental galectin inhibitors have often been developed with a close resemblance to natural disaccharide ligands, such as lactose and N-acetyllactosamine (lacNAc) [15] via thiodigalactosides [16][17][18][19], as adding a second monosaccharide unit to

• most potent galectin-1 inhibitor 1b has at least fiftyfold better affinity than the reference monosaccharide methyl β-D-galactoside (11) and a similar affinity as the reference disaccharide methyl β-lactoside (12). Hence, the 4-fluorophenyltriazol moiety of 1b efficiently replaces the galectin-1

• selectivity than reported C-galactosides [22][23]. Monosaccharide derivatives with somewhat higher affinity for galectin-1 are known; dissociation constants down to 62 µM and selectivity of 8 over galectin-3 [34]. However, these inhibitors are larger and carry double modifications with an anomeric thiophenyl

Influence of per-O-sulfation upon the conformational behaviour of common furanosides

• Alexey G. Gerbst,
• Vadim B. Krylov,
• Dmitry A. Argunov,
• Maksim I. Petruk,
• Arsenii S. Solovev,
• Andrey S. Dmitrenok and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2019, 15, 685–694, doi:10.3762/bjoc.15.63

• drastic changes of the ring conformation occurred while sometimes only the conformation of the exocyclic C4–C5 linkage changed. Herein we describe a combined quantum chemical and NMR conformational investigation of three common monosaccharide furanosides as their propyl glycosides: α-mannose, β-glucose

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

• of the CbzF-protected aminopentanol 7 afforded the monosaccharide 8 (Scheme 2). The 2-O-position was then deacylated, followed by iterative glycosylation/deacetylation with donor 3 to provide dimannoside acceptor 11. TCA-mannose donor 3 was initially used to cap the dimannoside 11. However

Convergent synthesis of the pentasaccharide repeating unit of the biofilms produced by Klebsiella pneumoniae

• Arin Gucchait,
• Angana Ghosh and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2019, 15, 431–436, doi:10.3762/bjoc.15.37

• the oligosaccharide fragments corresponding to the capsular polysaccharides or polysaccharides secreted by the bacterial strains, is to develop effective synthetic strategies. The structure and glycosyl linkages of the monosaccharide units remain conserved in the synthesized oligosaccharides in

• using a set of stereoselective glycosylations of a number of suitably functionalized monosaccharide derivatives 2, 3 [14], 4, 5 [15], 6 [16] and 7 [17], which were prepared from the commercially available reducing monosaccharides using a number of functional group manipulations reported earlier (Figure

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

• and D-glucuronic acid (GlcA) acceptors. These results, together with those obtained from experiments employing model monosaccharide building blocks, highlight the impact of the glycosyl acceptor structure on the stereoselectivity of glycosylation reactions. Our study provides useful data about the

• -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

• , which act as FimH antagonists, for example, have been successfully used to significantly reduce the severity of E. coli infections of the urinary tract in mice [66]. Furthermore, preliminary clinical trials with D-mannose indicate promising effects of this monosaccharide on controlling urinary tract

• well as the monosaccharide D-arabinose, were both found to reverse agglutination, while the α-L-arabinofuranoside-, β-L-arabinopyranoside-, and β-D-galactopyranoside-containing larch wood arabinogalactan and the corresponding L-arabinose monosaccharide were ineffective. Furthermore, the yeast

Synthesis of a sucrose-based macrocycle with unsymmetrical monosaccharides "arms"

• Karolina Tiara,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2018, 14, 634–641, doi:10.3762/bjoc.14.50

• -O-benzylsucrose with different unsaturated monosaccharide units is presented. Such a highly functionalized intermediate was cyclized under RCM conditions to afford a macrocyclic derivative containing a 31-membered ring in 26% yield. Keywords: chiral macrocycles; ring-closing metathesis; sucrose

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

• developed approaches which employed donor and acceptor monosaccharide molecules that were already functionalized with the lipid chains and phosphate groups [75][76], the new synthetic route used orthogonally protected monosaccharide precursors 3 and 4 (Scheme 1). The glycosyl donor 3 was synthesised

• reductive opening of the benzylidene acetal to give the acceptor monosaccharide 63. NIS/TMSOTf-promoted glycosylation of 63 with glycosyl donor 64 furnished desired β(1→6) disaccharide which was subjected to treatment with hydrazine hydrate to remove the phthalimido group. Subsequent acylation of the

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• 1 nor 2 were available, we instead modeled the monosaccharide–receptor interactions based on the available oligomannose crystal structures (PDB codes: 1K9J and 1SL4). In addition, because none of the available crystal structures of human MBP met our threshold of a resolution below 2 Å, we used a

An efficient synthesis of a C₁₂-higher sugar aminoalditol

• Łukasz Szyszka,
• Anna Osuch-Kwiatkowska,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2017, 13, 2146–2152, doi:10.3762/bjoc.13.213

• Lukasz Szyszka Anna Osuch-Kwiatkowska Mykhaylo A. Potopnyk Slawomir Jarosz Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland 10.3762/bjoc.13.213 Abstract The C12-aminoalditol H2NCH2–(CHOBn)10–CH2OH was prepared from two simple monosaccharide

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• disaccharide 7, which could be subjected to bromine-promoted glycosylation for further chain elongation. As an example, preactivation of a monosaccharide 8 with bromine was followed by the addition of a bifunctional disaccharide building block 10 and subsequent TMSOTf-promoted orthoester rearrangement

• with two arabinan chains each containing 31 D-arabinofuranose residues (Araf31). Both Galf30 and Araf31 fragments were prepared starting from monosaccharide building blocks. As an example, a six component preactivation-based glycosylation using the p-TolSCl/AgOTf promoter system and three

• monosaccharide building blocks (106–108) led to the formation of hexasaccharide 109 in an excellent 63% yield in one pot on a gram scale (Scheme 19a). This is the largest number of glycosylation reactions that have been performed in one pot to date. Further iterative five-component one-pot glycosylation (111