Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• using established procedures from the literature, commencing with ᴅ-glucosamine and benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-α-ᴅ-glucopyranoside as the starting materials, respectively [40][41][42][43]. Imidate donors 1a and 1e were obtained exclusively as α-anomers, and 1b and 1g as a 1:1 α:β

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

• ion trap mass analyzer. The following monosaccharides were analyzed: three stereoisomers of hexosamine of chemical formula C6H13NO5, namely glucosamine (GlcN), galactosamine (GalN), mannosamine (ManN); and N-acetyl glucosamine (GlcNAc, chemical formula C8H15NO6). One typical spectrum of each of the

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

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

• 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

Shift of the reaction equilibrium at high pressure in the continuous synthesis of neuraminic acid

• Jannis A. Reich,
• Miriam Aßmann,
• Kristin Hölting,
• Paul Bubenheim,
• Jürgen Kuballa and
• Andreas Liese

Beilstein J. Org. Chem. 2022, 18, 567–579, doi:10.3762/bjoc.18.59

• the position of the reaction equilibrium. By this, equilibrium conversion, selectivity, and yield were increased from 57.9% to 63.9%, 81.9% to 84.7%, and 47.5% to 54.1%, respectively. This indicates a reduction in molar volume from N-acetyl-ᴅ-glucosamine (GlcNAc) and pyruvate (Pyr) to Neu5Ac. In

• -acetyl-ᴅ-glucosamine and pyruvate. In addition, pressure up to 130 MPa was used to increase the conversion by 6.0%, the selectivity by 2.8%, and the yield by 6.7% (from 57.9% to 63.9%, 81.9% to 84.7%, and 47.4% to 54.1%, respectively). The increase in the value of the equilibrium constant with pressure

• epimerase (N-acyl-ᴅ-glucosamine 2-epimerase, EC 5.1.3.8) from Pedobacter heparinus was ordered as codon optimized gBlocks gene fragment (Integrated DNA Technologies, Leuven, Belgium). The gene for the aldolase (N-acetylneuraminate lyase, EC 4.1.3.3) was amplified from the genomic DNA of Escherichia coli K12

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

• pattern. Although still lacking control over the polymer length, these compounds underscored the importance of well-defined polysaccharides to understand the microscopic properties of natural xylans and fuel advancements in plant cell-wall biology [102]. Glucosamine-based polysaccharides Chitin and

• well-defined COS, but it is to date underexploited. The poor reactivity of the C-4 hydroxy group of the glucosamine BB, and the need of orthogonal PGs on the nitrogen atom to control the PA are the main bottlenecks [251]. The β-directing N-phthaloyl (N-Phth) PG was installed in trichloroacetimidate

• glycosylation or complicating the deprotection steps. Orthogonality and stability become particularly crucial when the goal is the multistep synthesis of long COS. Other glucosamine-based polysaccharides Other polymers of glucosamine based on the β(1–3) or β(1–6) linkages exist, but have gained less synthetic

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

• modulating their protein affinity, metabolic stability, and lipophilicity. Here we described the synthesis of a series of mono-, di- and trifluorinated N-acetyl-ᴅ-glucosamine and ᴅ-galactosamine analogs. The key intermediates are the corresponding multiply fluorinated glucosazide and galactosazide

• ]. 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

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• bacteria [57]. It is a glycolipid consisting of a variable polysaccharide domain connected to a conserved glucosamine-based phospholipid called lipid A. It is highly negatively charged due to two phosphorylated groups in the lipid A part and carboxylated groups in the polysaccharide part. It is amphiphilic

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

• )-ᴅ-glucosamine disaccharide 1-phosphate) (Figure 1). The synthesis of such precursors is particularly important as it will facilitate the aforementioned goal of harnessing the immunostimulatory effects of lipid A through development of a clear understanding of the structure–activity relationship

• with LiOH gave (R)-3-(2-naphthylmethoxy)tetradecanoic acid (7) in 78% yield over two steps. The glucosamine building block 14 was synthesized using the procedures described in previous literature [20] (Scheme 2). The protection of the free amine of glucosamine with a 2,2,2-trichloroethoxycarbonyl (Troc

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

• ]. Recently, Sigida and co-workers reported the structure of the tetrasaccharide repeating unit of the O-specific polysaccharide of Azospirillum doebereinerae type strain GSF71T, which is composed of three α-ʟ-rhamnose units and one β-ᴅ-glucosamine moiety [21]. It also contains two O-acetyl groups which might

• . 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

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

• . albertii O4 strain [11], which is a pentasaccharide comprising of α-linked ᴅ-galactosamine, β-linked ᴅ-glucosamine, β-linked ᴅ-galactose, α-linked ʟ-fucose and α-linked ʟ-rhamnose moieties. In the recent past, several vaccine candidates have been developed to control bacterial infections by conjugating

• stereoselective glycosylation of compound 14 with ᴅ-glucosamine thioglycoside donor 7 furnished the desired pentasaccharide derivative 15 in 70% yield. The formation of compound 15 with appropriate configuration at the glycosidic linkages was supported by its NMR spectral analysis [signals at δ 5.64 (d, J = 3.5

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• ). Conversion of benzylated reducing sugars, such as glucose [15], N-acetyl-ᴅ-glucosamine [16], and galactose [17], into the corresponding C-glycosyl phosponates using a Wittig reaction with methylenetriphenylphosphorane furnished the respective glycoenitols, which were then subjected to mercuriocyclization

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

• supported by theoretical studies [10][11]. ᴅ-Galactose (ᴅ-Gal) is one of the most abundant sugars in nature and a component of oligosaccharides and glycoconjugates with relevant functions [12]. Following a methodology previously applied to ᴅ-glucosamine acceptors [8] with some modifications, in the present

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

• , 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

Towards the preparation of synthetic outer membrane vesicle models with micromolar affinity to wheat germ agglutinin using a dialkyl thioglycoside

• Dimitri Fayolle,
• Nathalie Berthet,
• Bastien Doumeche,
• Olivier Renaudet,
• Peter Strazewski and
• Michele Fiore

Beilstein J. Org. Chem. 2019, 15, 937–946, doi:10.3762/bjoc.15.90

• to prevent the binding to primary sites. Conclusion A series of glucose and N-acetyl glucosamine-based thioglycolipids were synthesized for the first time by using thiol–ene coupling in the absence of protecting groups and in good yields. Monosaccharides where selected on the basis of similar

• , bearing one or two N-acetyl glucosamine moieties are capable to bind strongly to the lectin WGA. Experimental Materials and methods Myristoyl chloride was from TCI-Europe (Antwerp, Belgium) and used without further purification. 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphate (POPC) was from Avanti Polar

• Lipids (Alabaster, AL, USA). 2,3,4,6-Tetra-O-acetyl-α--glucopyranosyl bromide and N-acetyl--glucosamine were from Carbosynth (San Diego, CA, USA). Wheat germ agglutinin (WGA), horseradish peroxidase-labelled WGA (WGA-HRP), bovine serum albumin (BSA) and SIGMA FAST O-phenylenediamine dihydrochloride (OPD

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

• acceptance results in the same cell-surface labeling intensity due to its superior reactivity in the DAinv reaction. Based on the high incorporation efficiency of the Cp derivative we synthesized and investigated two new Cp-modified glucosamine and galactosamine derivatives. Both compounds lead to comparable

• , distinct cell-surface staining after MGE. We further found that the amide-linked Cp-modified glucosamine derivative but not the Cyoc-modified glucosamine is metabolically converted to the corresponding sialic acid. Keywords: bioorthogonal chemistry; carbohydrates; cyclopropenes; inverse electron-demand

• acceptance of the Cp-modified sugar inspired us to develop novel derivatives of glucosamine and galactosamine containing this cyclopropene modification and to explore their behavior in MGE both for membrane-bound and intracellular glycoproteins. Results and Discussion Kinetic studies The second-order rate

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

• host proteins and cell types, for example the invariant N-acetyl-D-glucosamine or N-acetyl-D-galactosamine residues that attach N- or O-glycans, respectively, to the peptide side chains, the large variety and possible permutations of “capping” residues (for example D-mannopyranosides, D

• membrane is surrounded by a peptidoglycan layer (PG) consisting of multiple, parallel glycan chains of alternating (1→4)-linked subunits of N-acetyl-β-D-glucosamine and N-acetyl- or N-glycolyl-β-D-muramic acid, crosslinked via short conserved oligopeptide stems [44][45]. The PG is covalently attached to

• : filamentous hemagglutinin; L-Fucp: L-fucopyranoside; D-Galf: D-galactofuranoside; D-Galp: D-galactopyranoside; D-GlcNAc: N-acetyl-D-glucosamine; D-Glcp: D-glucopyranoside; HBHA: heparin-binding hemagglutinin; KDO: 3-deoxy-D-manno-octulosonic acid; LAM: lipoarabinomannan; LM: lipomannan; LPS

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

• -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

• catalysis are currently under investigation. This will hopefully provide insight into the mechanism of the Tsuji–Trost reaction with our ligands which will lead to further improvement of our spiro-PHOX ligands. General structure of PHOX ligands 1 and structures of annulated glucosamine-based PHOX and PyOx

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

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

• for completion to afford the corresponding azido compound 7 in 82% yield. As anticipated, the anomeric azidation of peracetylated ribofuranose (Table 1, entry 7) proceeded well even at 0 °C within 2 h to give the product in 93% yield. However, the azidation of peracetylated 2-deoxy-D-glucosamine was

• slow and required one equivalent of AuBr3 and heating at 55 °C for 48 h to reach completion. In this case the desired product β-azido 2,3,4,6-acetyl-D-glucosamine (9) could be obtained in 74% yield. The need of using higher amounts of catalyst in this reaction could be attributed to the possible

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• chlorines to the methyl group did increase their potency [19][20][21][22][23]. However, applications were still less widespread than more conventional glucosamine-derived donors. Resurgent interest in the production of glycosyl oxazolines, and in particular oxazoline derivatives of N-glycans, was as a

• glycosylation of the OH-4 of a selectively protected glucosamine acceptor has been used more than the other methods. Selective and orthogonal protection of OH-2 of the donor by an ester group facilitates both the stereoselective formation of the desired β-linkage, and also access to OH-2 after glycosylation for

• the incorporation of tags into the glycan structure, which allows further modifications to be made later. In this case, following conversion of the azide at position 2 of the glucosamine unit into an acetamide, azide was introduced at position 6 of the two terminal mannose residues. Protecting group

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

• and Salmonella [2][26], ethanolamine in Helicobacter pylori, 4-amino-4-deoxy-β-L-arabinose (β-L-Ara4N) [27][28] in E. coli [29], Burkholderia [27] and Yersinia pestis [30] or galactosamine in Francisella [2][26], and glucosamine in Bordetella species [31] (Figure 2). Covalent attachment of aminosugar

• based on the initial preparation of the orthogonally protected glucosamine disaccharide 48 [99]. Initial acylation of the free OH group in position 3, followed by sequential manipulation of the amino-protecting groups (2’-N-Troc and 2-N-Alloc) and acylation with the corresponding branched (R)-3

• oligosaccharide, hydrolysis of the 1-phosphate from the reducing end glucosamine, and removal of the acyl chain from position 3 of the disaccharide backbone [59]. Lower toxicity of the TLR4 ligand MPLA compared to its parent LPS/lipid A was linked to the absence of the phosphate group in position 1 of the

Diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside: synthesis, derivatives and antimicrobial activity

• Henryk Myszka,
• Patrycja Sokołowska,
• Agnieszka Cieślińska,
• Andrzej Nowacki,
• Maciej Jaśkiewicz,
• Wojciech Kamysz and
• Beata Liberek

Beilstein J. Org. Chem. 2017, 13, 2310–2315, doi:10.3762/bjoc.13.227

• -amino-2-deoxy-β-D-glucopyranoside [31]. Monoethyl derivatives of both glucosamine and galactosamine are the most active compounds against Gram-positive bacteria in the tested groups, regardless of the fact that hydrochloride of aminogalactoside 5 is completely inactive with respect to the tested

• -ethyl derivative of D-glucosamine. Apart from N-ethyl also N-acetyl and 2-chloroethylureido derivatives exhibit activity against Gram-positive bacteria. The change of D-glucosamine into D-galactosamine in diosgenyl 2-amino-2-deoxy-β-D-glycopyranoside impairs the antimicrobial properties of its

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

• thioglycoside donor 136 was preactivated through anodic oxidation, followed by the addition of the acceptor 137 to afford disaccharide 138 (Scheme 20). Repeating this process, a series of oligo-glucosamine ranging from tri- to hexa-saccharides 139–142 was successfully prepared. 2-Deoxy and 2,6-dideoxyglycosides

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• -configured acceptor 78 was used the (1→4)-linked product 81 was formed exclusively in 82% yield with high α-selectivity. Similarly, when mannose, glucosamine, and glucal were used as glycosyl acceptors, the 1→4 linkage was formed exclusively with high α-selectivity in 92%, 77%, and 72% yield, respectively