An efficient synthesis of 1,6-anhydro-N-acetylmuramic acid from N-acetylglucosamine

• Matthew B. Calvert,
• Christoph Mayer and
• Alexander Titz

Beilstein J. Org. Chem. 2017, 13, 2631–2636, doi:10.3762/bjoc.13.261

• -AnhydroGlcNAc (2-acetamido-1,6-anhydro-2-deoxy-α-D-glucopyranoside, 4, Scheme 2) can be prepared in two steps from GlcNAc [11], and this molecule was thus used as the starting point for our synthetic studies. Initial attempts to alkylate anhydroGlcNAc 4 directly gave a complex mixture of stereo- and

• C-6, and between H-4 and the quarternary trityl carbon (Figure 2, green single-headed arrows). NOESY correlations between the trityl group and the GlcNAc protons on the lower face of the ring further confirmed the expected structure (Figure 2, blue double-headed arrows; see Supporting Information

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• ligation of an oxazoline donor and commercially available RNase B protein (with the glycans curtailed to a single GlcNAc moiety [17]) as the acceptor [16]. The beauty of this work extends beyond the enzymatic glycosylation reaction. We point out that the oxazoline functionality was installed chemically in

• be coupled to form a diphosphate (plus some dimerized UMP–UMP) that is fully isolatable. Adding to the power of this method is the ability for the in situ formed diphosphate to react enzymatically with for example the known GlcNAc analog shown in Scheme 29 using either an inverting (shown) or

• reaction. Encouragingly this methodology has now being picked up by other research groups. In 2015, Cairo and colleagues used this methodology to mount GSH Gal, Lac, and GlcNAc moieties onto sepharose-binding beads very simply for the use in affinity chromatography which were suitable for binding lectins

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

• surface entropy and hinder crystal packing. For this reason, it is sometime necessary to manipulate the glycoform to facilitate the crystallization. In the case of the human IgE-FcεRIα [31], Man5-GlcNAc-GlcNAc-Asp-linked glycoforms produced better crystals than in the case where only the Man-GlcNAc-GlcNAc

• weeks [32]. Nevertheless, in the large majority of glycosylated structures, only the electron density map of the initial N-linked GlcNAc is present and can be modelled. In most of the cases, the glycan chains are exposed to the solvent and highly flexible. In such instances, the glycan can be modelled

• the biosynthesis of glycosidic linkage requires the transfer of a sugar residue from a donor to an acceptor [35]. Acceptor substrates are carbohydrates, proteins, lipids, DNA, flavonol, antibiotics and steroids. In contrast, glycosyl donor substrates are mostly sugar nucleotides, such as UDP-GlcNAc

Correction: Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 1136–1138, doi:10.3762/bjoc.13.112

• structures in Schemes 9, 15, 20, and 22. The corrected schemes are shown in this Correction. The wrong configuration was depicted for C-4 (carrying the OH group) in the pyranose ring of doxorubicin in Scheme 9; the corrected scheme (Scheme 1) is shown below: The NH group was missing at C-2 of the GlcNAc

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• thio-amphiphilic linker to impart improved solubility and flexibility to the glycosyl-ligand. UV–vis spectroscopy and dynamic light scattering measurements have been exploited to detect at low picomolar concentrations lactose-AuNP, mannose-AuNP and GlcNAc-AuNP interactions with their cognate lectins

Synthesis of multi-lactose-appended β-cyclodextrin and its cholesterol-lowering effects in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2017, 13, 10–18, doi:10.3762/bjoc.13.2

• to its hydrophilicity and relatively high molecular weight. The asialoglycoprotein receptor (ASGPR), a hepatic galactose or N-acetylglucosamine (GlcNAc) receptor, is highly expressed on the sinusoidal cell surface of hepatocytes. ASGPR is responsible for the binding, internalization, and subsequent

• clearance of glycoproteins containing terminal galactose or GlcNAc residues from the circulation [12]. Hence, galactosylated nanocarriers have been utilized for the selective delivery of drugs to the liver via ASGPR-mediated endocytosis [13]. In fact, ASGPR-mediated endocytosis is one of the promising

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• : Bacterial cell walls consist of peptidoglycan, a heteropolymer with long chains of alternating units of N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc) that are cross-linked through peptide chains attached to the muramic acid sugar (Figure 3) [52]. The biosynthesis of peptidoglycan is

• , transformation to a disaccharide and transport to the extracellular side of the membrane (Figure 4, steps B, C); finally, polymerisation to long oligosaccharide chains and cross-linking occur (Figure 4, steps D, F). In the cytosol, uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc), that is formed from

• been reported elsewhere [52]. The membrane-associated steps commence with the transfer of UDP-MurNAc-pentapeptide to the lipid carrier undecaprenyl phosphate, catalysed by translocase I (MraY), to give lipid I (Figure 4, product of step B). The glycosyltransferase MurG attaches a GlcNAc sugar to

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• 2) [2]. The remarkable ability of acetylated fluoro analogs of GlcNAc and GalNAc to perturb the (glycosamino)glycan biosynthesis and their antiproliferative properties aroused our interest in developing a methodology for the preparation of a complete series of acetylated 3-fluoro, 4-fluoro-, and 3,4

• -difluoro analogs 1, 4–8 (Figure 1) including previously unknown members of this class of hexosamine mimics: acetylated 3-fluoro-D-GalNAc 6, 3,4-difluoro-D-GlcNAc 7 and 3,4-difluoro-D-GalNAc 8, as well as 3-fluoro-D-GlcNAc 5, in which case the reported synthesis was troublesome and low-yielding [20]. To

• in terms of product purity. Hydrogenolysis of 42 on palladium in ethanol/HCl followed by acetylation of the amino group furnished the target acetylated 3-fluoro-D-GlcNAc 5 as a chromatographically separable mixture of anomers (Table 1). Addition of HCl was found necessary to effect a clean

Mycothiol synthesis by an anomerization reaction through endocyclic cleavage

• Shino Manabe and
• Yukishige Ito

Beilstein J. Org. Chem. 2016, 12, 328–333, doi:10.3762/bjoc.12.35

• Gram-negative bacteria. MSH undergoes metal-catalyzed autoxidation more rapidly than glutathione [16]. The biosynthetic pathway of MSH has been well investigated; MSH is synthesized from 1-inositol phosphate and uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) in five steps [15]. It is used by

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• singlet at δ = 7.78 ppm confirming the cycloaddition of derivatives 3 and 10. D-Glucosamine is an essential constituent of many naturally occurring oligosaccharides such as bacterial and fungal cell walls. Mainly, it is available as N-acetylglucosamine in β-glycosidic linkages (β-D-GlcNAc) [37

• and they varied insignificantly with each other. Finally, modified cholesterols with a bromohexyl arm (12), a GlcNAc residue (17), a maltoside tag (24) and even the triazole bridged bicholesterol (13) showed medium cytotoxic effects within the range of 18.3–21.5 μM and they varied insignificantly with

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

• , the insertion of an N-acetylglucosaminyl moiety (GlcNAc-) into an oligosaccharide chain was identified as the crucial step catalyzed by N-acetylglucosaminyltransferases (GnTs) in the presence of a metal co-factor. In this catalytic reaction, UDP-GlcNAc [uridine 5′-(2-acetamido-2-deoxy-D-glucopyranosyl

• diphosphate)] acts as the donor of the GlcNAc residue while a hydroxy group situated at a specific site of the growing oligosaccharide chain serves as the acceptor [9]. The target-directed search for effective GnTs inhibitors based on the rational design of model compounds remains a difficult task due to the

Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

• Laura Morelli,
• Damiano Cancogni,
• Marta Tontini,
• Alberto Nilo,
• Sara Filippini,
• Paolo Costantino,
• Maria Rosaria Romano,
• Francesco Berti,
• Roberto Adamo and
• Luigi Lay

Beilstein J. Org. Chem. 2014, 10, 2367–2376, doi:10.3762/bjoc.10.247

• experienced a dramatic drop of the overall yield during the conversion of the azido groups in acetamides on protected glycosyl phosphosaccharide intermediates [25]. We therefore sought to design a different strategy based on GlcNAc instead of azido glucose building blocks, where the azide reduction is rather

Expanding the scope of cyclopropene reporters for the detection of metabolically engineered glycoproteins by Diels–Alder reactions

• Anne-Katrin Späte,
• Verena F. Schart,
• Julia Häfner,
• Andrea Niederwieser,
• Thomas U. Mayer and
• Valentin Wittmann

Beilstein J. Org. Chem. 2014, 10, 2235–2242, doi:10.3762/bjoc.10.232

• staining. The staining intensity resulting from the galactosamine derivative 2 was in between. Previous work from Bertozzi and coworkers suggests that GlcNAc derivatives such as N-azidoacetylglucosamine (GlcNAz) can only enter cell-surface glycans via less efficient conversion of GlcNAz to N

• -azidoacetylmannosamine (ManNAz) and subsequently to the corresponding sialic acid [32][33] following a metabolic pathway known also for the natural sugars [34]. Also, the efficiency by which non-natural GlcNAc and GalNAc derivatives are metabolized is dependent on the type of modification and the cell line. These

• -acetamido-2-deoxy-D-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc) (Sigma-Aldrich) (100 µM) (O-GlcNAc-β-N-acetylglucosaminidase inhibitor to maintain O-GlcNAcylation during lysis) and incubated at 4 °C for 30 min. The lysate was cleared by centrifugation (22,000g, 30 min, rt). Tz–biotin 10 was added to

Orthogonal dual thiol–chloroacetyl and thiol–ene couplings for the sequential one-pot assembly of heteroglycoclusters

• Michele Fiore,
• Gour Chand Daskhan,
• Baptiste Thomas and
• Olivier Renaudet

Beilstein J. Org. Chem. 2014, 10, 1557–1563, doi:10.3762/bjoc.10.160

• binary combinations of α-D-Man or β-D-GlcNAc, thus providing rapid access to attractive heteroglycosylated platforms for diverse biological applications. Keywords: chemoselective ligation; heteroglycocluster; multivalency; multivalent glycosystems; one-pot synthesis; Introduction Multivalent

• sugar 1 is mandatory to avoid its addition during the TCC reaction. After purification, compound 4 was obtained in 46% yield and subsequently subjected to the TCC reaction with β-D-GlcNAcSH 2 under conditions described above. Compound 5, wherein α-D-Man and β-D-GlcNAc occupied at the upper and the lower

• reactions give clean reaction mixtures to provide the hGC 11 with 77% yield. The same strategy was followed to prepare compound 13 featuring two α-D-Man and four β-D-GlcNAc. No difference of reactivity was observed whatever the scaffold or the glycosyl thiol used. All these products were obtained in good

Design, automated synthesis and immunological evaluation of NOD2-ligand–antigen conjugates

• Marian M. J. H. P. Willems,
• Gijs G. Zom,
• Nico Meeuwenoord,
• Ferry A. Ossendorp,
• Herman S. Overkleeft,
• Gijsbert A. van der Marel,
• Jeroen D. C. Codée and
• Dmitri V. Filippov

Beilstein J. Org. Chem. 2014, 10, 1445–1453, doi:10.3762/bjoc.10.148

• -acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) of which the lactic acid is connected to a peptide [24]. Where NOD1 recognizes diaminopimelic acid containing peptides [25][26], the minimal structural element of PG required for activation of the intracellular protein NOD2 is N-acetylmuramyl-L-alanine-D

• comparable to MDP derivative 20. The difference in the activity of conjugates 2 and 3 compared to 4 and 5 indicates that the attachment point of the MDP to the antigenic peptide is important. Conjugation at the GlcNAc anomeric center of MDP as in conjugates 4 and 5 is more favorable than conjugation to the

Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

• Felix Wojcik,
• Sinaida Lel,
• Alexander G. O’Brien,
• Peter H. Seeberger and
• Laura Hartmann

Beilstein J. Org. Chem. 2013, 9, 2395–2403, doi:10.3762/bjoc.9.276

• introduced in the desired pattern by automated solid-phase synthesis. As a proof of principle we synthesized glycoligand 16 as a multivalent scaffold that presents two different monosaccharides. β-GlcNAc and β-Gal are exposed in alternating fashion with an overall oligomer length of six building blocks and a

The Amadori rearrangement as glycoconjugation method: Synthesis of non-natural C-glycosyl type glycoconjugates

• Katharina Gallas,
• Gerit Pototschnig,
• Florian Adanitsch,
• Arnold E. Stütz and
• Tanja M. Wrodnigg

Beilstein J. Org. Chem. 2012, 8, 1619–1629, doi:10.3762/bjoc.8.185

• conjugation of carbohydrate moieties to suitable amino components. Starting from selected aldoheptoses, which are readily available by means of the Kiliani–Fischer C-elongation reaction of the corresponding aldohexoses, glycoconjugates presenting D-gluco, D-manno and D-galacto as well as GlcNAc motifs have

• -natural C-glycosyl type glycoconjugates in the D-manno, D-galacto as well as GlcNAc series starting from the respective aldoheptoses and suitable amino components. Aldoheptoses were synthesised by C-elongation of the corresponding hexoses and subsequent reductive hydrolysis following the Kiliani–Fischer

• method in hand, D-galactose (14), D-mannose (17) as well as GlcNAc (20) were successfully converted to the corresponding aldoheptoses (Scheme 4), namely D-glycero-L-manno/L-gluco-heptopyranose 16a and 16b, D-glycero-D-galacto/D-talo-heptopyranose 19a and 19b, and 3-acetamido-3-deoxy-D-gluco-D-ido/D-gulo

Synthesis of 4” manipulated Lewis X trisaccharide analogues

• Christopher J. Moore and
• France-Isabelle Auzanneau

Beilstein J. Org. Chem. 2012, 8, 1134–1143, doi:10.3762/bjoc.8.126

• adenocarcinomas. In addition, an association between the fucosylation of internal GlcNAc residues in polylactosamine chains, and metastasis and tumor progression in colorectal cancers has been suggested [1][2][3][4][5][6]. Unfortunately, dimLex displays the Lex trisaccharide (β-D-Galp(1→4)[α-L-Fucp(1→3)]-D

High-affinity multivalent wheat germ agglutinin ligands by one-pot click reaction

• Henning S. G. Beckmann,
• Heiko M. Möller and
• Valentin Wittmann

Beilstein J. Org. Chem. 2012, 8, 819–826, doi:10.3762/bjoc.8.91

• Triticum vulgaris by an enzyme-linked lectin assay (ELLA) employing covalently immobilized N-acetylglucosamine (GlcNAc) as a reference ligand. IC50 values were in the low micromolar/high nanomolar range, depending on the linker between the two disaccharides. Binding enhancements β up to 1000 for the

• (WGA), besides other plant lectins such as Con A, has been intensively employed as a model lectin to study the influence of the structure of multivalent ligands on the binding affinity. WGA ligands of defined structure containing two to twelve GlcNAc residues obtained either by individual synthesis [28

• acid and N-acetylglucosamine (GlcNAc) and has been shown to inhibit fungal growth through interaction with fungal cell-wall components [40][41][42] and to agglutinate transformed cells in vitro [43][44]. Recently, we determined the structural basis of multivalent binding to WGA by X-ray crystallography

Synthetic glycopeptides and glycoproteins with applications in biological research

• Ulrika Westerlind

Beilstein J. Org. Chem. 2012, 8, 804–818, doi:10.3762/bjoc.8.90

• glycopeptide/glycoprotein synthesis, Endo-A specific for high-mannose glycans and Endo-M operating on both high-mannose and complex type N-glycans [81][82][83]. These enzymes can, in contrast to glycosyltransferases, by means of a one-step reaction attach large oligosaccharides to a GlcNAc polypeptide. Until

• 39 used in this study contained a mixture of high-mannose glycoforms; by treatment with endoglycosidase H (Endo-H), these glycans could be hydrolytically cleaved leaving the GlcNAc monosaccharide still attached to the protein. By treatment with a complex type glycan oxazoline donor and an Endo-M

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

• Grazia Marano,
• Claas Gronewold,
• Martin Frank,
• Anette Merling,
• Christian Kliem,
• Sandra Sauer,
• Manfred Wiessler,
• Eva Frei and
• Reinhard Schwartz-Albiez

Beilstein J. Org. Chem. 2012, 8, 787–803, doi:10.3762/bjoc.8.89

• ]. Furthermore, the overexpression of the charged blood group antigen sialyl Lewisx consisting of the terminal NeuNAcα2-3Galβ1-4(Fucα1-3)GlcNAc-group is correlated with carcinogenesis. It is recognized and bound by selectins, which are a subgroup of lectins that play an important role as cell-surface molecules

Formation of carbohydrate-functionalised polystyrene and glass slides and their analysis by MALDI-TOF MS

• Martin J. Weissenborn,
• Johannes W. Wehner,
• Christopher J. Gray,
• Robert Šardzík,
• Claire E. Eyers,
• Thisbe K. Lindhorst and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2012, 8, 753–762, doi:10.3762/bjoc.8.86

• -mercaptoundecanoic acid (1), which is tritylated with 2 in a straightforward synthesis, in 98% yield, following the procedure of Kovács et al. [23] (Scheme 1). The acid 3 was coupled with either of the aminoethyl glycosides 4 [24][25][26] or the GlcNAc derivative 6 [27], which were prepared according to literature

• , but it is not necessary to cover the slide fully. Given that the MS analysis on the polystyrene was successful, we attempted an enzymatic galactosylation of GlcNAc–Trt 7 using bovine β-(1→4)-galactosyltransferase (β-(1→4)-GalT, EC 2.4.1.38) on the polystyrene slides. This enzymatic transformation has

• proven to be a very reproducible and robust reaction, which appears to proceed to completion on gold arrays [31] and is routinely performed in our laboratory. After treatment of slides containing GlcNAc–Trt 7 with the enzyme by using previously reported procedures [31], followed by washing procedure 1

Chemo-enzymatic modification of poly-N-acetyllactosamine (LacNAc) oligomers and N,N-diacetyllactosamine (LacDiNAc) based on galactose oxidase treatment

• Christiane E. Kupper,
• Ruben R. Rosencrantz,
• Birgit Henßen,
• Helena Pelantová,
• Stephan Thönes,
• Anna Drozdová,
• Vladimir Křen and
• Lothar Elling

Beilstein J. Org. Chem. 2012, 8, 712–725, doi:10.3762/bjoc.8.80

• the semipreparative production of oxidised products. The methyl β-galactoside was chosen as a reference substance because of the comparable linkage at the anomeric C-atom and its known high activity [38]. No activity could be seen with odd-numbered (GlcNAc-terminated) poly-LacNAc–linker–t-Boc

• experiment (bold printed in tables) and confirmed by the downfield glycosylation shift of the involved carbons (C-4 for Glc, C-3 for Gal). Chemical shifts of GlcNAc carbons C-2 agree with N-acetylation. Because of isomerism on the NH-C=S bond, signals of H-1A and CS were not detected. Chemical shifts of

• spin system –(CH2)4CHCH(N–)CH(N–)CH2– of biotin. The anomeric configuration (β) of all saccharide units was determined from the JH-1,H-2 coupling constants. Chemical shifts of GlcNAc carbons C-2 agree with N-acetylation. Because of isomerism on the NH–C=S bond, protons H-1A resonate as two broad

Coupled chemo(enzymatic) reactions in continuous flow

• Ruslan Yuryev,
• Simon Strompen and
• Andreas Liese

Beilstein J. Org. Chem. 2011, 7, 1449–1467, doi:10.3762/bjoc.7.169

• conversions in the range of 95–98%. The continuous enzymatic synthesis of N-acetylneuraminic acid (17) from N-acetylglucosamine (GlcNAc, 14) in an enzyme membrane reactor employing two enzymes was developed by Kragl and coworkers [27]. In their coupled-reaction system the first enzyme GlcNAc 2-epimerase

The allylic chalcogen effect in olefin metathesis

• Yuya A. Lin and
• Benjamin G. Davis

Beilstein J. Org. Chem. 2010, 6, 1219–1228, doi:10.3762/bjoc.6.140

• selenide protein tag is a requirement for most effective CM. Allyl and hexenyl ethers were found to be the most compatible CM partners for allyl sulfide or selenide containing proteins. The more challenging alkene substrates, such as the ones containing electron-deficient N-acetylamine, GlcNAc and

• GlcNAc, mannose and N-acetylamine, which could serve as effective mimics of post-translational protein modifications (glycosylation, lysine acetylation). Conclusion Since the early work by Hoye on secondary allylic alcohols [19] and later the studies on allyl sulfides by our group [17], the allyl