Monitoring carbohydrate 3D structure quality with the Privateer database

• Jordan S. Dialpuri,
• Haroldas Bagdonas,
• Lucy C. Schofield,
• Phuong Thao Pham,
• Lou Holland and
• Jon Agirre

Beilstein J. Org. Chem. 2024, 20, 931–939, doi:10.3762/bjoc.20.83

• the diagram. For example, a shape with an orange highlight indicates something is abnormal about the ring’s conformation, puckering, or monosaccharide nomenclature [30]. Similarly, a linkage with an orange highlight indicates that the torsion angles between the linkages are unexpected and require

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

• (CFG), with its logical and appealing monosaccharide symbols has fortunately now become standard. Cartoons like this can be generated by GlycanBuilder [8][9], Glyconnect [10], GlyTouCan [7], GlycoWorkbench [9], SugarSketcher [11][12] or GlycoDraw [13] or by a universal graphics program such as, e.g

• box at the bottom connects abbreviated monosaccharide names with proglycan shorthand names and SNFG symbols. Annotation of antennae with galactose and sialic residues with consideration of linkage options. Note that the use of superscript format for linkages is recommended style but optional as it

Comparison of glycosyl donors: a supramer approach

• Anna V. Orlova,
• Nelly N. Malysheva,
• Maria V. Panova,
• Nikita M. Podvalnyy,
• Michael G. Medvedev and
• Leonid O. Kononov

Beilstein J. Org. Chem. 2024, 20, 181–192, doi:10.3762/bjoc.20.18

• during purification by silica gel chromatography. On the other hand, NMR analysis of the crude reaction mixtures may be misleading due to possible overlap of the signals of H-3eq belonging both to disaccharide and monosaccharide derivatives sometimes present in such glycosylation mixtures. At low

GlAIcomics: a deep neural network classifier for spectroscopy-augmented mass spectrometric glycans data

• Thomas Barillot,
• Baptiste Schindler,
• Baptiste Moge,
• Elisa Fadda,
• Franck Lépine and
• Isabelle Compagnon

Beilstein J. Org. Chem. 2023, 19, 1825–1831, doi:10.3762/bjoc.19.134

• ), thus providing valuable additional isomer resolution [4]. We demonstrated that this multidimensional MS–IR molecular fingerprint is unique to each carbohydrate building block and can be used to resolve their full sequence, including their monosaccharide content and the detail of their linkages

• each monosaccharide unit is measured, and subsequently identified by comparison with a library of reference spectra of synthetic monosaccharide standards. In the early days of MS–IR spectroscopy, ca. one hour was necessary to record the IR fingerprint of a single molecule and the identification was

• probabilistic deep neural network (Bayesian deep neural networks [12]) to support automated monosaccharide recognition for carbohydrate sequencing. We obtained a highly performing algorithm that we called "GlAIcomics", specifically trained on carbohydrates. Methodology Data production Our carbohydrate analysis

Sulfur-containing spiroketals from Breynia disticha and evaluations of their anti-inflammatory effect

• Ken-ichi Nakashima,
• Naohito Abe,
• Masayoshi Oyama,
• Hiroko Murata and
• Makoto Inoue

Beilstein J. Org. Chem. 2023, 19, 1604–1614, doi:10.3762/bjoc.19.117

• ′′′′. The linkages in the sugar moiety were determined based on the HMBC correlations of H-1′/C-3, H-1′′/C-2′, H-1′′′/C-3′′′, and H-1′′′′/C-2′′ and the SSCCs of the anomeric protons. The sugars contained in 1 and their absolute configurations were confirmed by analyzing the monosaccharide mixture obtained

• 13.96 and 22.16 min were coincident with those of the ᴅ-glucose and ʟ-rhamnose derivatives, respectively. Although the peak at 20.83 min was assumed to be attributable to apiofuranose, we were unable to obtain any standard for apiofuranose. In the reported monosaccharide identification method, the

• ], these differences indicate that the sulfoxide moieties in the aglycone of 1 and 2 are isomers. The remaining NMR resonances (Table 2) and 2D NMR spectroscopic data (Figure 2) showed that the glycosyl group of 2 was the same as that of 1. This assignment was further supported by HPLC-based monosaccharide

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Linker, loading, and reaction scale influence automated glycan assembly

• Marlene C. S. Dal Colle,
• Manuel G. Ricardo,
• Nives Hribernik,
• José Danglad-Flores,
• Peter H. Seeberger and
• Martina Delbianco

Beilstein J. Org. Chem. 2023, 19, 1015–1020, doi:10.3762/bjoc.19.77

• purification steps. Keywords: automated glycan assembly; photocleavable linker; polysaccharides; solid-phase synthesis; Introduction Automated glycan assembly (AGA) is a solid-phase method that enables the rapid synthesis of complex oligo- and polysaccharides from protected monosaccharide building blocks

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

• one of a few examples of chemical synthesis of chitin oligosaccharides through polyglycosylation of a glucosamine monosaccharide [6]. Recently, we have reported electrochemical polyglycosylation using a glucosamine derivative as a monomer [7]. This is another example of polyglycosylation of a

• glucosamine monosaccharide. However, N-acetylglucosamines are linked by α-1,4-glycosidic bonds. Here, we report electrochemical polyglycosylation of thioglycosides to produce protected precursors of chitin oligosaccharides. Results and Discussion Optimization of electrochemical polyglycosylation We initiated

• , also showed low conversion (63%). However, it gave pentasaccharide 5d in the highest yield (6%) among these four thioglycosides. Based on these results, we optimized the reaction using thioglycoside 1a, which afforded oligosaccharides 2a–6a and recovered monosaccharide 1a in the highest total yield (88

Terpenoids from Glechoma hederacea var. longituba and their biological activities

• Dong Hyun Kim,
• Song Lim Ham,
• Zahra Khan,
• Sun Yeou Kim,
• Sang Un Choi,
• Chung Sub Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2022, 18, 555–566, doi:10.3762/bjoc.18.58

• of 2 were similar to those of substolide A except for signals of the methoxy group attached to C-8 and of a monosaccharide at C-6 in 2 [12]. The planar structure of 2 was established based on 2D NMR spectroscopic data (COSY, HSQC, and HMBC). The HMBC correlation from H-1' (δH 4.42) to C-6 (δC 76.6

• the same methods as those used for 1. As a result, the monosaccharide of 2 was identified as ᴅ-glucose (Figure S17, Supporting Information File 1). The anomeric proton configuration of the glucopyranosyl unit was determined to be β-configuration based on the J value (7.7 Hz) [11]. Thus, the structure

• identification were performed and monosaccharide of 3 was identified as ᴅ-glucopyranose (Supporting Information File 1, Figure S26). Thus, the structure of 3 was determined as (1R,4R,5S, 6S,10S)-1,10;4,5-diepoxy-6-O-β-ᴅ-glucopyranosyl-glechomafuran. Compound 4 was purified as a colorless gum. The HRESIMS

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• typically found as a terminal unit of surface glycoconjugates and is crucial to various cellular recognition events in both physiological and pathological processes [1]. This distinctive negatively charged monosaccharide is the natural substrate for sialidases, which belong to different glycoside hydrolase

• series of C-2-modified sialic acid bearing a monosaccharide tethered via 1,2,3-triazole ring (sialylmimetic neoglycoconjugates) [19] that showed 67–91% inhibitory activity at 1 mM. We now envisaged replacing the monosaccharide moiety by (hetero)aromatic substituents (Figure 2A) expecting better

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

• authors [39][40][41][42]. The starting materials 3, 6, and 7 were also amenable to a [1 + 1 + 1] one-pot synthetic strategy by adopting minor synthetic modifications. The monosaccharide building blocks 3, 6, and 7 [43] were synthesized from previously reported compounds 8 [36], 9 [44][45], and 10 [46] as

• described in Scheme 2. With the monosaccharide building blocks in hand, the galactosamine donor 6 was coupled with galactose acceptor 7 by activation of the thioglycoside using N-iodosuccinimide (NIS) in the presence of TMSOTf to afford the desired disaccharide β-ᴅ-GalpNHTroc-(1→4)-α-ᴅ-Galp (4) in 85% yield

• monosaccharide acceptor 7 was added, followed by the addition of NIS and TMSOTf. After 15 min of reaction, TLC monitoring showed complete consumption of the donor. Work-up of the reaction mixture followed by chromatographic purification afforded the pure trisaccharide 2 as a single isomer in an overall yield of

GlycoBioinformatics

• Kiyoko F. Aoki-Kinoshita,
• Frédérique Lisacek,
• Niclas Karlsson,
• Daniel Kolarich and
• Nicolle H. Packer

Beilstein J. Org. Chem. 2021, 17, 2726–2728, doi:10.3762/bjoc.17.184

• proteomic data into a glycomic context by harvesting information about glyco-related genes and proteins. Glycobioinformatics requires additional information about the expressed glycan, including but not limited to monosaccharide composition, full or partial sequence including linkage and branching structure

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

• a solid support following a linear approach (Figure 1D). Cycles of glycosylation and selective deprotection are iteratively performed to access the desired polysaccharide with full control over the length and the monosaccharide sequence [32]. Upon completion of the assembly, the desired product is

• towards the synthesis of well-defined polysaccharides, with particular focus on how to control the length and the substitution pattern. Each section describes a class of polysaccharides based on a particular monosaccharide backbone (Figure 2). For each class, we discuss the specific challenges associated

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

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• -containing 1,2,3-triazole derivatives 30 from the reaction of glycosyl azides 28 with enolates of active ketones and esters 29 in the presence of DBU in DMF at 70 °C (Scheme 12) [43]. Diverse monosaccharide and disaccharide azides were successfully reacted with a variety of enolates of active ketones and

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

• ; Introduction Alginate is an important, industrially relevant polysaccharide chemically composed of β-1,4-linked ᴅ-mannuronic acid (M) and α-ʟ-guluronic acid (G) monosaccharide building blocks (Figure 1a). Because of its biocompatibility, alginate has several commercial industrial applications; for example, it

• appropriate chemoenzymatic syntheses [21][22][23]. Conclusion We have established synthetic access to a series of C6-tetrazole thioglycoside monosaccharide building blocks with capability for orthogonal C4- and tetrazole N-protecting groups. We demonstrate anomeric manipulation of these donors to new

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

• ]. Unprotected multiply-deoxyfluorinated N-acetyl-ᴅ-glucosamine (GlcNAc) and N-acetyl-ᴅ-galactosamine (GalNAc) have not yet been described except for a 4,6-difluoro-GalNAc analog [22], although GlcNAc is the most abundant monosaccharide component of mammalian glycans [23], and GalNAc occurs in important glycan

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

• 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

• . The method involves a set of regular-expression-based rules acting on strings of characters that representing the monosaccharide units, x, model the actions of transferases in the general form, Ax + B = A + xB, where Ax is a nucleotide sugar and B is the carbohydrate moiety of the acceptor, be it a

• before sugars units, and multiple modifiers on the same monosaccharide are again ordered by linkage position, from lowest to highest, reading right to left. Nomenclature of gangliosides Gangliosides are commonly labelled according to the abbreviated Svennerholm [20] nomenclature, or else by the expanded

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

• rules (SRS), modification rules (MR), branch rules (BR), repetition rules (RR), glycoconjugate rules (GR), and uncertainty rules (UR). The saccharide unit (SU) refers to a structure with four elements: anomericity, position number, modifications, and monosaccharide (MS). Stereospecificity and ring

• ). Similarly, galactofuranose, a common fungal monosaccharide, would be written “A^” Open form rule indicates that if the MS at the reducing end is open – a linear rather than cyclic MS, then the final character to the right of the string should be "o". For example, lactose, galactose β-linked to glucose would

• α-2,6-linked sialic acid (NNa6) whose linkage position is unknown. Here, the “ | ” is used to separate the fragment(s) and core structure components (UR6). In the interest of demonstrating the reach of single letter LC monosaccharides (Table 4), we provide a monosaccharide network suggesting

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

• monosaccharide minimal-energy conformation. While these features were recognised to address some long-standing needs in carbohydrate structure determination [39][40], significant challenges remain, particularly in the scenario where the glycan composition cannot be ascertained solely from the three-dimensional

• ]. Typically, these analyses are based on mass spectrometry techniques, such as electrospray ionization mass spectrometry (ESIMS) and matrix-assisted laser desorption ionization MS (MALDIMS) [43]. Mass spectrometry techniques are best suited for the determination of the composition of monosaccharide classes

• their generalized composition classes, i.e., Hex, HexNAc, dHex, NeuAc, etc. The identity elucidation of generalized unit classes into specific monosaccharide units (such as Glc, Gal, Man, GalNAc, etc.) requires prior knowledge of the glycan biosynthetic pathways [46]. Additional sources of prior

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

• nomenclatures available to describe each monosaccharide, representing and encoding a glycan structure into a file is required for communication among scientists as well as for data processing. As a consequence, glycobiologists have proposed different graphical representations, with symbols or chemical

• of completion, the full description of a monosaccharide should obey the following rules: monosaccharide code>[]. It is thus necessary to include such information

• impossible to build the required depiction. It emerges that an efficient carbohydrate builder must offer a wide array of options to characterise and personalise each monosaccharide. This would, in turn, entail a multitude of buttons, switches, etc.; which would result in a very complex interface

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