Automated synthesis of sialylated oligosaccharides

• Davide Esposito,
• Mattan Hurevich,
• Bastien Castagner,
• Cheng-Chung Wang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 1601–1609, doi:10.3762/bjoc.8.183

• this important class of molecules. The automated synthesis of oligosaccharides has been significantly improved since the first report in 2001 [4]. Currently, the platform enables the rapid assembly of complex oligosaccharides and accommodates the most commonly employed glycosylation reactions [5][6][7

• the glycosylation of building blocks 1, 8 and 10 with galactal 2 under similar conditions (Table 1, entries 1–3). Sialylation with building block 8 failed to yield any disaccharide 9 (Table 1, entry 1), while glycosylating agents 10 and 1 gave moderate yields and good selectivity (Table 1, entries 2

• and 3). The glycosylation of galactal 2 with phosphite 1, which we described in the supporting information of [5], was further optimized. In particular, elevating the reaction temperature proved beneficial and disaccharide 9 was isolated in higher overall yield, albeit with a slight decrease in

Studies on the substrate specificity of a GDP-mannose pyrophosphorylase from Salmonella enterica

• Lu Zou,
• Ruixiang Blake Zheng and
• Todd L. Lowary

Beilstein J. Org. Chem. 2012, 8, 1219–1226, doi:10.3762/bjoc.8.136

• -benzylidene-α-D-mannopyranoside (19) [26] was first methylated giving 20 and then converted into glycosyl acetate 21 in 49% yield over the two steps. Subsequent thioglycosylation provided a 52% yield of 22. The protected dibenzyl phosphate 23 was next formed by the NIS–AgOTf promoted glycosylation of dibenzyl

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

• is modified at O-4 as a methyloxy, deoxychloro or deoxyfluoro, were synthesized. We first report the preparation of the modified 4-OMe, 4-Cl and 4-F trichloroacetimidate galactosyl donors and then report their use in the glycosylation of an N-acetylglucosamine glycosyl acceptor. Thus, we observed

• that the reactivity of these donors towards the BF3·OEt2-promoted glycosylation at O-4 of the N-acetylglucosamine glycosyl acceptors followed the ranking 4-F > 4-OAc ≈ 4-OMe > 4-Cl. The resulting disaccharides were deprotected at O-3 of the glucosamine residue and fucosylated, giving access to the

• toward glycosylation [64][65][66]. However, we have reported the successful O-4 glycosylation of an N-acetylglucosamine monosaccharide acceptor using peracetylated gluco- and galactopyranose α-trichloroacetimidate donors under activation with 2 equivalents of BF3·OEt2 at room temperature or 40 °C [14][67

Synthesis and structure of tricarbonyl(η⁶-arene)chromium complexes of phenyl and benzyl D-glycopyranosides

• Thomas Ziegler and
• Ulrich Heber

Beilstein J. Org. Chem. 2012, 8, 1059–1070, doi:10.3762/bjoc.8.118

• reacting acetobromoglucose with 6-tert-butyl-2-hydroxypyridine [20] under Helferich conditions (Hg(CN)2). Only the corresponding O-glycoside 1l was obtained, and no N-glycoside was formed in this Helferich glycosylation (Scheme 1). Sterically hindered 6-tert-butyl-2-hydroxypyridine was chosen as the

• . Treatment of pentaacetylglucose and 2-tert-butylphenol with BF3-etherate in dichloromethane afforded 1o in 31% yield. Glycoside 1p was prepared by a Helferich glycosylation of o-methylbenzyl alcohol with acetobromoglucose. For further details see Supporting Information File 1. Table 2 summarizes the results

The use of glycoinformatics in glycochemistry

• Thomas Lütteke

Beilstein J. Org. Chem. 2012, 8, 915–929, doi:10.3762/bjoc.8.104

• that it provides information on proteins to which specific glycans were found to be attached, including details on glycosylation sites. The Japan Consortium for Glycobiology and Glycotechnology DataBase (JCGGDB) [34] provides a collection of individual databases that are cross-linked with each other

• used to create models of carbohydrate chains. The latter program can also perform in silico glycosylation by adding the glycan chains to a protein 3D structure, and provides input files for the AMBER [94][95] modeling programs using the GLYCAM force field [99]. Glycan 3D structures calculated by Sweet

• CHARMM [97] input files from PDB files that contain carbohydrates. Various tools to predict the occupancy state of potential glycosylation sites from protein sequence data are available as well (Table 5). If a protein–carbohydrate complex is to be modeled, generally available docking tools such as

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

• -tuning of native chemical ligation (NCL), expressed protein ligation (EPL), and chemoenzymatic glycosylation techniques have all together enabled the synthesis of functional glycoproteins. The synthesis of structurally defined, complex glycopeptides or glyco-clusters presented on natural peptide

• glycosylation sites, is valuable for functional biological studies. Glycopeptides have, for instance, been applied to evaluate the role of conformational and proteolytic stability [6]. In other studies, synthetic glycopeptides have been employed in vaccines to induce specific immune responses or for the

• the discovery, by Springer et al., that glycoproteins on the outer cell membrane of epithelial tumor cells have an altered glycosylation consisting of the Thomsen-Friedenreich (T-) antigen and its precursor TN-antigen structure, the synthesis and evaluation of anti-tumor vaccines have been a topic of

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

• among cells are mediated by binding of proteins such as lectins to oligosaccharides. Upon progression to higher malignancy, the glycosylation patterns of glycoproteins and glycosphingolipids on tumor cell surfaces undergo several alterations [6]. These changes are closely associated with distinct

• cellular processes, such as adhesion to the ECM, and modulation of the tumor-associated microenvironment, which represent advantages for the capacity of the cell to invade the host tissue and to secure undisturbed growth [7]. The glycosylation pattern of tumor cells is therefore the focus in the

• , represents a strong candidate for the design of saccharide mimetics to be used as anti-tumor drugs. Results and Discussion Syntheses of saccharide mimetics Glycosylation of 3,4-bis(hydroxymethyl)furan (1) with 1.0 equiv imidate 2 in CH2Cl2 afforded 48% of monosaccharide 3. The synthesis of (4-{[(β-D

Synthesis and antifungal properties of papulacandin derivatives

• Marjolein van der Kaaden,
• Eefjan Breukink and
• Roland J. Pieters

Beilstein J. Org. Chem. 2012, 8, 732–737, doi:10.3762/bjoc.8.82

• glycal 18, led us to compound 37. This compound opens the way to a total synthesis of disaccharides such as the papulacandins A–C. Selective protection of the hydroxy group of C(6) followed by glycosylation of the hydroxy group at C(4), should accomplish this. In our biological assay we did not see any

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

• 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

• singlets. The above-mentioned spin systems were put together by using information extracted from the 1H,13C HMBC experiment (diagnostic correlations are bold printed in the Tables NMR 5 and NMR 6 in Supporting Information File 2). The glycosidic linkage was also demonstrated by the downfield glycosylation

An easy α-glycosylation methodology for the synthesis and stereochemistry of mycoplasma α-glycolipid antigens

• Yoshihiro Nishida,
• Yuko Shingu,
• Yuan Mengfei,
• Kazuo Fukuda,
• Hirofumi Dohi,
• Sachie Matsuda and
• Kazuhiro Matsuda

Beilstein J. Org. Chem. 2012, 8, 629–639, doi:10.3762/bjoc.8.70

• one-pot α-glycosylation method was effectively applied. The synthetic GGPL-I isomers were characterized with 1H NMR spectroscopy to determine the equilibrium among the three conformers (gg, gt, tg) at the acyclic glycerol moiety. The natural GGPL-I isomer was found to prefer gt (54%) and gg (39

• the cytoplasm fluid membrane together with ubiquitous phospholipids, without inducing stereochemical stress. Keywords: cytoplasm membrane; glycolipid antigen; glycosylation; mycoplasma; stereochemistry; Introduction Mycoplasmas constitute a family of gram-positive microbes lacking rigid cell walls

• access to both a natural GGPL-I homologue (C16:0) and its diastereomer I-a and I-b, in which our one-pot α-glycosylation methodology [25][26] is effectively applied. The two GGPL-I isomers prepared thereby were characterized with 1H NMR spectroscopy, in terms of configuration and conformation at the

2-Allylphenyl glycosides as complementary building blocks for oligosaccharide and glycoconjugate synthesis

• Hemali D. Premathilake and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2012, 8, 597–605, doi:10.3762/bjoc.8.66

• activated for chemical glycosylation under a variety of conditions, through both direct and remote pathways. Differentiation between the two activation pathways was achieved in a mechanistic study. The orthogonal-type activation of the AP moiety along with common thioglycosides allows for the execution of

• efficient oligosaccharide assembly. Keywords: carbohydrates; glycosylation; leaving group; oligosaccharides; orthogonal strategy; selective activation; Introduction Current knowledge about the key roles of carbohydrates is still limited. However, thanks to the explosive growth of the field of glycobiology

• particularly stimulating for major scientific efforts in the field of modern glycosciences. The traditional chemical synthesis of oligosaccharides is lengthy because it involves multiple manipulations of protecting and/or leaving groups between glycosylation steps [5]. Many advanced strategies that shorten the

Electrochemical generation of 2,3-oxazolidinone glycosyl triflates as an intermediate for stereoselective glycosylation

• Toshiki Nokami,
• Akito Shibuya,
• Yoshihiro Saigusa,
• Shino Manabe,
• Yukishige Ito and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2012, 8, 456–460, doi:10.3762/bjoc.8.52

• temperatures. However, α-selectivity was observed in the absence of base at elevated reaction temperatures. In situ generated triflic acid promotes the isomerization of β-products to α-products. Keywords: amino sugar; anomerization; electrochemical oxidation; glycosylation; thioglycoside; Introduction

• glycosylations via glycosyl triflate intermediates. In this paper, we report the generation, accumulation, and characterization by low-temperature NMR analyses, of the corresponding glycosyl triflates. Electrochemical glycosylation of the thioglycoside donor with 2,3-oxazolidinone protecting group gave both 1,2

• carbon is around 100 ppm in all cases and the corresponding cross peaks of the anomeric protons and carbons were observed in HMQC spectra. Using electrochemically generated glycosyl triflate 2a, the stereoselectivity of the glycosylation was investigated by the addition of five equiv of various alcohols

Facile synthesis of nitrophenyl 2-acetamido-2-deoxy-α-D-mannopyranosides from ManNAc-oxazoline

• Karel Křenek,
• Petr Šimon,
• Lenka Weignerová,
• Barbora Fliedrová,
• Marek Kuzma and
• Vladimír Křen

Beilstein J. Org. Chem. 2012, 8, 428–432, doi:10.3762/bjoc.8.48

• , Czech Republic 10.3762/bjoc.8.48 Abstract The synthetic procedures for a large-scale preparation of o- and p-nitrophenyl 2-acetamido-2-deoxy-α-D-mannopyranoside are described. The synthetic pathway employs the glycosylation of phenol with ManNAc oxazoline, followed by nitration of the aromatic moiety

• yielding a separable mixture of the o- and p-nitrophenyl derivative in a 2:3 ratio. Keywords: α-ManNAc; glycosidase; glycosylation; nitrophenyl; oxazoline; Introduction Hexosamines are fundamental structural elements and precursors of the peptidoglycan and membrane lipopolysaccharide layer as well as of

• % yield) or from methyl 4,6-O-benzylidene-α-D-glucopyranoside (5 steps, 23%). Unfortunately, in our hands this synthetic procedure did not afford the published yields, namely in the triflate and consequent azide substitution steps. Oxazolines, such as 3, have been used as glycosylation agents in the

Acceptor-influenced and donor-tuned base-promoted glycosylation

• Stephan Boettcher,
• Martin Matwiejuk and
• Joachim Thiem

Beilstein J. Org. Chem. 2012, 8, 413–420, doi:10.3762/bjoc.8.46

• glycosylation is a recently established stereoselective and regioselective approach for the assembly of di- and oligosaccharides by using partially protected acceptors and glycosyl halide donors. Initial studies were performed on partially methylated acceptor and donor moieties as a model system in order to

• analyze the key principles of oxyanion reactivities. In this work, extended studies on base-promoted glycosylation are presented by using benzyl protective groups in view of preparative applications. Emphases are placed on the influence of the acceptor anomeric configuration and donor reactivities

• . Keywords: glycosylation; oxyanion; reactivity; regioselectivity; Introduction For the assembly of oligosaccharides the complex and challenging control of regio- and stereochemistry has to be solved. Various contributions have facilitated enormously the access to complex oligosaccharide structures so far

Dependency of the regio- and stereoselectivity of intramolecular, ring-closing glycosylations upon the ring size

• Patrick Claude,
• Christian Lehmann and
• Thomas Ziegler

Beilstein J. Org. Chem. 2011, 7, 1609–1619, doi:10.3762/bjoc.7.189

• –d, to give the corresponding 2-[3-(alkylcarbamoyl)propionyl] tethered saccharides 5a–d. Intramolecular, ring closing glycosylation of the saccharides with NIS and TMSOTf afforded the tethered β(1→3) linked disaccharides 6a–c, the α(1→3) linked disaccharides 7a–d and the α(1→2) linked disaccharide 8d

• in ratios depending upon the ring size formed during glycosylation. No β(1→2) linked disaccharides were formed. Molecular modeling of saccharides 6–8 revealed that a strong aromatic stacking interaction between the aromatic parts of the benzyl and benzylidene protecting groups in the galactosyl and

• glucosyl moieties was mainly responsible for the observed regioselectivity and anomeric selectivity of the ring-closing glycosylation step. Keywords: intramolecular glycosylation; molecular modeling; prearranged glycosides; Introduction Intramolecular O-glycosidic bond formation of tethered glycosyl

Convergent synthesis of the tetrasaccharide repeating unit of the O-antigen of Shigella boydii type 9

• Abhishek Santra and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2011, 7, 1182–1188, doi:10.3762/bjoc.7.137

• achieved in excellent yield using a [2 + 2] block glycosylation strategy. TEMPO-mediated selective oxidation of the primary alcohol of the tetrasaccharide derivative 8 to the carboxylic group followed by deprotection of the functional groups furnished target tetrasaccharide 1 as its 4-methoxyphenyl

• glycoside in high yield. Keywords: diarrhea; glycosylation; O-antigen; oligosaccharide; Shigella boydii; Introduction Diarrhoeal disease is a common cause of death in the tropical countries and it is the second mostly causing infant deaths worldwide. Shigella is one of the well-studied human pathogens

• towards the preparation of glycoconjugates, we report herein a convergent chemical synthesis of the tetrasaccharide as its 4-methoxyphenyl glycoside 1 corresponding to the O-antigen of Shigella boydii type 9 using a [2 + 2] block glycosylation strategy (Figure 2). Results and Discussion The convergent

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• glycosylations have appeared in recent years. Ph3PAuOTf is reported to be a superior catalyst (yield increases by >20%) compared to conventionally used ZnCl2 for the well-established glycosylation reaction with 1,2-anhydrosugars 66 as donors (Scheme 14) [39]. The gold(I)-catalyzed reaction of 2,3,4,6-tetra-O

• in the presence of propargyl glycosides and propargyl ethers was developed [41]. Recently, Li et al. reported the gold(I)-catalyzed glycosylation with glycosyl ortho-alkynylbenzoates 73 as donors [42]. This glycosylation protocol was used in an efficient synthesis of a cyclic triterpene

Synthesis of glycoconjugate fragments of mycobacterial phosphatidylinositol mannosides and lipomannan

• Benjamin Cao,
• Jonathan M. White and
• Spencer J. Williams

Beilstein J. Org. Chem. 2011, 7, 369–377, doi:10.3762/bjoc.7.47

• : α-Man-1,6-α-Man, α-Man-1,6-α-Man-1,6-α-Man, α-Man-1,2-α-Man-1,6-α-Man and 2,6-di-(α-Man)-α-Man. The synthesis includes the use of non-benzyl protecting groups compatible with the azido group and preparation of the branched trisaccharide structure 2,6-di-(α-Man)-α-Man through a double glycosylation

• achieved by glycosylation of 14 with the thioglycoside donor 21 [41] using NIS/TfOH in 84% yield (Scheme 4). The protected trisaccharide 25 was prepared by an approach similar to that reported for the corresponding octyl trisaccharide [22][23]. Thus glycosylation of 14 with the silylated donor 22 using NIS

• -glycosylation could be achieved to allow the subsequent synthesis of the α-Man-1,2-Man linkage (Scheme 5). Activation of a mixture of alcohol 14 and trichloroacetimidate 16 at 0 °C with 0.1 equiv of BF3·Et2O provided disaccharide 26 in only 21% yield, with a 1,2-glycosyl orthoester as the major product (40

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

• 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

Catalysis: transition-state molecular recognition?

• Ian H. Williams

Beilstein J. Org. Chem. 2010, 6, 1026–1034, doi:10.3762/bjoc.6.117

• complex: it attacks the anomeric carbon of the substrate as a nucleophile and displaces the aglycone nucleofuge (Scheme 3). Glu172 is protonated in the reactant complex and plays a dual role of acid/base catalyst: in the glycosylation step it assists formation of the glycosyl-enzyme intermediate by

A bivalent glycopeptide to target two putative carbohydrate binding sites on FimH

• Thisbe K. Lindhorst,
• Kathrin Bruegge,
• Andreas Fuchs and
• Oliver Sperling

Beilstein J. Org. Chem. 2010, 6, 801–809, doi:10.3762/bjoc.6.90

•  2) [28][29]. Glycosylation of the acceptor diol 11 with the trichloroacetimidate 12 [30] led to mannotrioside 13 with the required azidoethyl aglycone. Reduction of the azido group gave amine 15 and subsequent peptide coupling reaction with Gly5Boc with inexpensive coupling reagents led to the

Preparation of aminoethyl glycosides for glycoconjugation

• Robert Šardzík,
• Gavin T. Noble,
• Martin J. Weissenborn,
• Andrew Martin,
• Simon J. Webb and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2010, 6, 699–703, doi:10.3762/bjoc.6.81

• ; glycoarrays; glycoconjugation; glycosylation; Introduction The chemical conjugation of carbohydrates through the anomeric centre to biomolecules such as peptides, proteins, lipids, metabolites and to array surfaces is an important synthetic challenge [1][2][3][4][5]. A diverse range of linkers and spacers

• 2-chloroethanol under acid catalysis, followed by peracetylation, nucleophilic substitution with azide and finally, reduction of the azido group [13][14]. Alternatively, the carbohydrate was first activated as the trichloroacetimidate or bromide followed by glycosylation with N-Cbz-aminoethanol [15

• ], bromoethanol [16] or azidoethanol [17] and subsequently transformed into the amine. In the interest of finding fast reliable methods, we have investigated two general aminoethylation protocols: First, the direct glycosylation of peracetylated sugars, which can be either purchased or easily prepared from free

Synthesis of 6-PEtN-α-D-GalpNAc-(1–>6)-β-D-Galp-(1–>4)-β-D-GlcpNAc-(1–>3)-β-D-Galp-(1–>4)-β-D-Glcp, a Haemophilus influenzae lipopolysacharide structure, and biotin and protein conjugates thereof

• Andreas Sundgren,
• Martina Lahmann and
• Stefan Oscarson

Beilstein J. Org. Chem. 2010, 6, 704–708, doi:10.3762/bjoc.6.80

• group patterns to improve the reactivity [20][21]. Here, however, NIS/AgOTf-promoted glycosylation of acceptor 13 with donor 3 proceeded without difficulties to produce the tetrasaccharide 14 in high yield (77%, Scheme 3). Before the introduction of the azido-galactose residue, the spacer azido function

• the acetamido carbonyl oxygen also partly behaved as a nucleophile and gave a pseudohexasaccharide acetimidate side product according to MALDI-TOF and NMR. Similar side products have earlier been described [25][26][27][28]. Mild acid treatment of the glycosylation mixture prior to purification led to

New amphiphilic glycopolymers by click functionalization of random copolymers – application to the colloidal stabilisation of polymer nanoparticles and their interaction with concanavalin A lectin

• Otman Otman,
• Paul Boullanger,
• Eric Drockenmuller and
• Thierry Hamaide

Beilstein J. Org. Chem. 2010, 6, No. 58, doi:10.3762/bjoc.6.58

• glycosylation yields, the scale-up of these reactions was shown to be difficult. As a spacer, we chose triethylene glycol. The reaction of 1 with 8-azido-3,6-dioxaoctyloctan-1-ol (prepared in several steps from triethylene glycol) [17] was found to be unsatisfactory since the by-products formed in the reaction

Synthesis of glycosylated β³-homo-threonine conjugates for mucin-like glycopeptide antigen analogues

• Florian Karch and
• Anja Hoffmann-Röder

Beilstein J. Org. Chem. 2010, 6, No. 47, doi:10.3762/bjoc.6.47

• increased biological half-life. Keywords: glycopeptide; glycosylamino acids; β3-homo-threonine; MUC1 antigens; solid-phase synthesis; Introduction Glycosylation is the predominant co- and post-translational modification in higher organisms responsible for tailoring and fine-tuning of the activity of

• proteins involved in fundamental biological recognition events of cell adhesion, cell differentiation and cell growth [1][2][3]. As a consequence, synthetic oligosaccharides and their conjugates are recognised as important tools for the expanding field of chemical biology [4]. Aberrant glycosylation of

• , glycosylation of the corresponding dipeptide precursor Fmoc-β3hThr(OH)-Ala-OBn failed completely. Therefore we encountered the strategy of Arndt–Eistert homologation in the synthesis of the target Fmoc-β3hThr(αAc3GalNAc) and Fmoc-β3hThr(β(Ac4Gal(1–3))α(Ac3GalNAc)) conjugates 2a and 4, respectively, as reported