Introduction of a human- and keyboard-friendly N-glycan nomenclature

• Friedrich Altmann,
• Johannes Helm,
• Martin Pabst and
• Johannes Stadlmann

Beilstein J. Org. Chem. 2024, 20, 607–620, doi:10.3762/bjoc.20.53

• -glycans, at least, no simple words. Next to chemical formulas, the IUPAC code can be regarded as the best, most reliable and yet immediately comprehensible annotation of oligosaccharide structures of any type from any source. When it comes to N-glycans, the venerable IUPAC code has, however, been widely

Synthesis of protected precursors of chitin oligosaccharides by electrochemical polyglycosylation of thioglycosides

• Md Azadur Rahman,
• Kana Kuroda,
• Hirofumi Endo,
• Norihiko Sasaki,
• Tomoaki Hamada,
• Hiraku Sakai and
• Toshiki Nokami

Beilstein J. Org. Chem. 2022, 18, 1133–1139, doi:10.3762/bjoc.18.117

• electrochemical polyglycosylation is also discussed, based on the oxidation potential of the monomer and oligosaccharides. Keywords: electrochemical glycosylation; glucosamine; oligosaccharide; oxidation potential; polyglycosylation; Introduction Chitin oligosaccharides are partial structures of chitin, which

• from natural sources or by synthesis via chemical glycosylation [2]. Total syntheses of chitin and chitosan oligosaccharides based on conventional chemical glycosylation of protected monosaccharides as building blocks have already been reported. Convergent synthesis using oligosaccharide building

Total synthesis of the O-antigen repeating unit of Providencia stuartii O49 serotype through linear and one-pot assemblies

• Tanmoy Halder and
• Somnath Yadav

Beilstein J. Org. Chem. 2021, 17, 2915–2921, doi:10.3762/bjoc.17.199

• was then deprotected and N-acetylated to finally afford the desired trisaccharide repeating unit as its α-p-methoxyphenyl glycoside. Keywords: capsular polysaccharide; carbohydrate vaccines; O-antigen; oligosaccharide synthesis; one-pot synthesis; Introduction O-antigens or O-specific

• development [1][2][3][4][5][6][7][8]. This objective has been proposed to be achieved by the synthesis of chemically homogeneous glycoconjugates bearing the O-antigen oligosaccharide conjugated to peptides for eliciting the desired immune response through vaccines [9][10][11][12][13][14][15][16][17][18][19

• may even lead to fatal bacteremia [22][25]. The structure of repeating oligosaccharide units of O-polysaccharides of several Providencia O-serogroups as well as P. stuartii O4 [26], O18 [27], O20 [28] O33 [29], O43 [30], O44 [31], O47 [32], and O57 [33] have been reported. With respect to the

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• approach (also known as fragment coupling) allows connecting pre-assembled oligosaccharide blocks. To decrease the synthetic time required for the chemical synthesis of polysaccharides, automated techniques have been developed [28][29][30][31]. Automated glycan assembly (AGA) connects monosaccharide BBs on

• less reactive adduct 31. DMF-mediated glycosylations permitted access to long structures based on multiple α(1–4) linkages 33 and 34 [178] and α(1–3) linkages 35 [179] (Scheme 5B). The short oligosaccharide 36 having α(1–2) linkages was also prepared, however, in this case, the stereoselectivity

• diminished with the increasing length of the oligosaccharide, possibly due to steric hindrance [180]. The nucleophilic modulation strategy in combination with the O-6-Lev remote anchimeric assistance could further improve the stereoselectivity of the 1,2-cis glycosylations, leading to the synthesis of long

A systems-based framework to computationally describe putative transcription factors and signaling pathways regulating glycan biosynthesis

• Theodore Groth,
• Rudiyanto Gunawan and
• Sriram Neelamegham

Beilstein J. Org. Chem. 2021, 17, 1712–1724, doi:10.3762/bjoc.17.119

• using ST6GALNAC3-6 and also ST8SIA1/3/5. 4) Dolichol pathway: This results in the formation of the dolichol-linked 14-monosaccharide precursor oligosaccharide. This glycan is cotranslationally transferred en bloc onto Asn-X-Ser/Thr sites of the newly synthesized protein as it enters the endoplasmic

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

• -protected donors, suitable for iterative oligosaccharide synthesis. The development of these building blocks is showcased to access anomeric 3-aminopropyl- and 1-phosphate free sugars containing this non-native motif. Keywords: alginate; glycosyl 1-phosphate; non-native monosaccharide; tetrazole; uronate

• this end, synthetic chemistry strategies (both solution and solid phase) have demonstrated exciting capabilities for access to native alginate oligosaccharides in recent years [6][7][8][9][10]. As part of a program to access non-native alginate oligosaccharide sequences, we targeted a synthetic

• oligosaccharide synthesis strategy. With such capability effectively demonstrated, we next explored the provision of ᴅ-manno C6-tetrazoles without an orthogonal C4-protecting group. Accordingly, a synthesis initiating from alcohol 15 [19] enabled access to C6-nitrile 16 in three steps (Scheme 4) and an improved

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• resulting from the low stability of amino sugar hemiacetals. The prepared polyfluorinated thiodonors and hemiacetals are valuable intermediates in oligosaccharide synthesis and their utility in glycosylation is currently being studied in our group. Retrosynthetic analysis of the target fluoro analogs

Simulating the enzymes of ganglioside biosynthesis with Glycologue

• Andrew G. McDonald and
• Gavin P. Davey

Beilstein J. Org. Chem. 2021, 17, 739–748, doi:10.3762/bjoc.17.64

• Gangliosides are glycosphingolipids that contain a sialylated carbohydrate linked to ceramide. Typically located in the plasma membranes of many tissues, gangliosides are most concentrated in the brain, where they are the dominant feature of the neuronal glycocalyx [1][2][3]. The oligosaccharide is based on a

• linear chain comprising of up to four monosaccharide units, containing glucose, galactose and N-acetylgalactosamine, to which are attached a variable number of sialic acid (N-acetylneuraminic acid) residues. The sialic acid content of the oligosaccharide, being anionic at pH 7, results in an overall

• glycolipid or some other oligosaccharide, the nucleotide A is the product of the donor and xB is the acceptor product. The strings can be seen as a compression of the familiar condensed linear IUPAC notation, using a single-letter notation to represent sugars, with upper-case denoting ᴅ, and lowercase, the ʟ

A consensus-based and readable extension of Linear Code for Reaction Rules (LiCoRR)

• Benjamin P. Kellman,
• Yujie Zhang,
• Emma Logomasini,
• Eric Meinhardt,
• Karla P. Godinez-Macias,
• Austin W. T. Chiang,
• James T. Sorrentino,
• Chenguang Liang,
• Bokan Bao,
• Yusen Zhou,
• Sachiko Akase,
• Isami Sogabe,
• Thukaa Kouka,
• Elizabeth A. Winzeler,
• Iain B. H. Wilson,
• Matthew P. Campbell,
• Sriram Neelamegham,
• Frederick J. Krambeck,
• Kiyoko F. Aoki-Kinoshita and
• Nathan E. Lewis

Beilstein J. Org. Chem. 2020, 16, 2645–2662, doi:10.3762/bjoc.16.215

• implementation of the reaction rules to accommodate the syntactic constraint of programming languages. A human milk oligosaccharide metaglycome was constructed using a combination of linear code, glycan structures represented in XML and XPath queries [39]. Separately, Akune et al. generated a theoretical N

Leveraging glycomics data in glycoprotein 3D structure validation with Privateer

• Haroldas Bagdonas,
• Daniel Ungar and
• Jon Agirre

Beilstein J. Org. Chem. 2020, 16, 2523–2533, doi:10.3762/bjoc.16.204

• . However, there are other methods that have been proven to successfully tackle the challenges posed by glycan heterogeneity, with mass spectrometry emerging as the one with the most relevance due to the ability to elucidate the complete composition descriptions of individual oligosaccharide chains on

• containing glycans that were previously unreported and inconsistent with glycan biosynthetic pathways. In particular, the model contained oligosaccharide chains with Man-(1→3)-GlcNAc and GlcNAc-(1→3)-GlcNAc linkages, β-galactosyl motifs capping oligomannose-type glycans and hybrid-type glycans containing

• anomer mismatch errors (the three letter code denoting one anomeric form did not match the anomeric form reflected in the atomic coordinates). After the anomer mismatch errors were corrected, the oligosaccharide chain also failed to return GlyTouCan and GlyConnect IDs. The other 11 chains that failed to

Computational tools for drawing, building and displaying carbohydrates: a visual guide

• Kanhaya Lal,
• Rafael Bermeo and
• Serge Perez

Beilstein J. Org. Chem. 2020, 16, 2448–2468, doi:10.3762/bjoc.16.199

• glycobiologists or any researcher looking for a ready to use, simple program for the sketching or building of glycans. Keywords: bioinformatics; carbohydrate; glycan; glycobiology; nomenclature; oligosaccharide; polysaccharide; representation; structure; Introduction Glycoscience is a rapidly surfacing and

• various force fields dedicated for carbohydrates. The accurately predicted oligosaccharide conformations are good starting points for further investigations. Of particular interest are the evaluations of the dynamics of glycans and their interactions with proteins which is a most significant concern in

• ://beta.glyco.me/sugarbuilder) is online software for drawing glycans. The interface leads to rapid carbohydrate construction. A panel of monosaccharide templates complements the drawing interface (one pre-built oligosaccharide is available (Figure 8, top). The user can start a chain from amino acid residues: Asn

The B & B approach: Ball-milling conjugation of dextran with phenylboronic acid (PBA)-functionalized BODIPY

• Patrizia Andreozzi,
• Lorenza Tamberi,
• Elisamaria Tasca,
• Gina Elena Giacomazzo,
• Marta Martinez,
• Mirko Severi,
• Marco Marradi,
• Stefano Cicchi,
• Sergio Moya,
• Giacomo Biagiotti and
• Barbara Richichi

Beilstein J. Org. Chem. 2020, 16, 2272–2281, doi:10.3762/bjoc.16.188

• regard, we recently reported on the straightforward synthesis of probe 1 (Figure 1) where a phenylboronic acid (PBA) moiety was introduced at the meso position of a BODIPY core. We demonstrated the compound’s ability to bind the oligosaccharide chain of the Fc domain of monoclonal antibodies, through the

Clustering and curation of electropherograms: an efficient method for analyzing large cohorts of capillary electrophoresis glycomic profiles for bioprocessing operations

• Ian Walsh,
• Matthew S. F. Choo,
• Sim Lyn Chiin,
• Amelia Mak,
• Shi Jie Tay,
• Pauline M. Rudd,
• Yang Yuansheng,
• Andre Choo,
• Ho Ying Swan and
• Terry Nguyen-Khuong

Beilstein J. Org. Chem. 2020, 16, 2087–2099, doi:10.3762/bjoc.16.176

• -throughput analysis [9]. In CE-LIF, released and fluorescently labelled glycans migrate over a capillary and are identified by comparison to the standardized migration time with external or internal oligosaccharide standards. In order to achieve standardized migration time in a high-throughput manner

• migration time of the 3 oligosaccharide standards that were separated with each sample. The migration times of glycan peaks were then translated to a calculated GU that made it easy to compare peaks and identify glycans across electropherograms (Figure 1B). Despite major misalignment of migration time 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

• bacteria and the environment [1]. For example, lipopolysaccharide (LPS) comprises the Gram-negative bacterial cell wall and is crucial in bacterial pathogenicity [2]. LPS is a complex molecule that is composed of three structural regions: lipid A (endotoxin), a non-repeating core oligosaccharide, and O

• -antigen [2]. While O-antigen and the core oligosaccharide are exposed to the external environment, lipid A, the hydrophobic domain of LPS, is embedded in the cell wall. The lipid A substructure is relatively conserved that consists of a β-1,6-linked diglucosamine with 1,4′-di-O-phosphorylation and 2,2′-N

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

• vaccines. The serotype 9V is part of the currently marketed conjugate vaccine and contains an acetate modification. To better understand the importance of glycan modifications in general and acetylation in particular, defined oligosaccharide antigens are needed for serological and immunological studies

• . Here, we demonstrate a convergent [2 + 3] synthetic strategy to prepare the pentasaccharide repeating unit of 9V with and without an acetate group at the C-6 position of mannosamine. Keywords: antigen; carbohydrate chemistry; oligosaccharide; Streptococcus pneumoniae; vaccines; Introduction

• oligosaccharide antigens are key to study the role of O-acetylation in protection and to confirm the structure of the natural RU. To date, only partial syntheses of the SP9A/V backbone have been reported but none have addressed the acetylation issue [25][26][27]. Oscarson et al. reported the synthesis of the

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

• isolating the polysaccharides by fermentation techniques, it is difficult to get a significant quantity of polysaccharide fragments from natural sources with adequate purity. Therefore, the development of chemical synthetic strategies is quite pertinent to obtain a requisite quantity of oligosaccharide

Regioselectivity of glycosylation reactions of galactose acceptors: an experimental and theoretical study

• Enrique A. Del Vigo,
• Carlos A. Stortz and
• Carla Marino

Beilstein J. Org. Chem. 2019, 15, 2982–2989, doi:10.3762/bjoc.15.294

• and one free hydroxy unit in order to achieve glycosylations with respect to the desired regiochemistry. The synthesis of such building blocks is usually the most time-consuming process of oligosaccharide synthesis [2][3]. The knowledge and control of glycosylation regioselectivity of building blocks

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

• protecting groups, whereby Fmoc was cleaved by piperidine (20 vol % in DMF), while Lev was removed using hydrazine acetate. Iterative cycles continued until the desired structure was obtained. The oligosaccharide products were cleaved from the solid support using a flow UV photoreactor, followed by a two

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

• chemically synthesized oligosaccharides before [8][9][10]. The corresponding aminopropyl linker has also been used by others [11]. The chemically synthesized oligosaccharide structure will help to elucidate further biological implications of the O-antigen concerned and possible vaccine potential. Results and

• Discussion It is important to select a suitable glycoside at the reducing end of the target oligosaccharide keeping in mind that the glycoside should allow further glycoconjugate formation without disturbing the stereochemistry of the anomeric center. Therefore, the 2-aminoethyl glycoside was selected at the

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

• designed, with a tethered fluorophore. Further attachment of the glycodendrimer to a biocompatible, surface eroding microparticle allows for targeted uptake and internalization of the pathogen-associated oligosaccharide by phagocytic immune cells. The α-1,2-trimannose-linked bioerodible microparticles were

• investigated how truncated oligosaccharide capping structures of LPG interact with macrophage pattern recognition receptors (PRRs) to modulate an innate immune response to L. major-induced leishmaniasis in vitro and in vivo [11][40][41][42]. These studies showed that a neutral α-1,2-trimannose capping

• allow for purification by FSPE of the mannosyl intermediates and to facilitate future automated syntheses to produce α-1,2-trimannose in appreciable quantities similar to previous efforts (Scheme 1) [11][47][51]. To synthesize the oligosaccharide, activation of TCA donor 3 with TMSOTf and glycosylation

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

• nucleic acids and (c) loss of homogeneity of the polysaccharide fragments to name a few. It has already been established that in many cases the oligosaccharide repeating units resemble similar antigenic potential to those of the native polysaccharides [8][9][10]. Therefore, the best alternative way to get

• 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

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

• oligosaccharides in order to improve the glycosylation efficiency [20][21]. In this approach, glucose instead of GlcA residues were employed in the oligosaccharide assembly and final oxidation and derivatization was carried out at the oligomer stage. Syndecan-1 glycopeptide containing a CS type A sequence was also

• assays, deprotection of dimer 6 and tetramer 14β were accomplished (Scheme 5). Compound 14α was also submitted to the deprotection sequence to obtain a non-natural α-containing oligosaccharide. Basic hydrolysis using H2O2/LiOH and then NaOH followed by selective N-acetylation in MeOH afforded CS

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

• cells exhibit a diverse array of glycoconjugates on their cell surfaces, together known as the glycocalyx (Figure 2). Carbohydrate moieties of the eukaryotic glycocalyx mainly exist in the form of oligosaccharide chains covalently linked to proteins or lipids. The most prevalent oligosaccharide

• -galactopyranosides, L-fucopyranosides and sialic acids) that comprise the most terminal, and therefore most accessible for lectin recognition, oligosaccharide regions contribute to a vast diversity of possible glycocalyx structures [40][41][42]. It is known, for example, that the carbohydrate composition of the

• of a phosphatidyl-myo-inositol core structure, glycosylated at the 2-position of myo-inositol [49][50][51]. The oligosaccharide of LM consists exclusively of linear (1→6)-linked and (1→2)-branched α-mannopyranosides [22], while in LAM the mannan structure is elongated by highly (1→2), (1→3) and (1→5

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

• pentasaccharide chain [5][6]. The pioneering work by Paulsen was later followed up by a total synthesis by the Ogawa group [7] and an oligosaccharide synthesis by the Magnusson group [8]. With the increasing understanding of glycobiology, the Forssman antigen has remained an interesting target for vaccine

• finding important for oligosaccharide synthesis. Here we describe this regioselective glycosylation approach in detail. Results and Discussion In the initial strategy for synthesizing the disaccharide, the fully protected acceptor (1 or 2) was intended to be a key building block. However, an unexpected