Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• , Tokushima, 770-8505, Japan 10.3762/bjoc.14.137 Abstract To synthesize nucleoside and oligosaccharide derivatives, we often use a glycosylation reaction to form a glycoside bond. Coupling reactions between a nucleobase and a sugar donor in the former case, and the reaction between an acceptor and a sugar

• used for the glycosylation of glycals and thioglycosides to produce disaccharides. In this paper, we review the use of hypervalent iodine-mediated glycosylation reactions for the synthesis of nucleosides and oligosaccharide derivatives. Keywords: glycosylation; hypervalent iodine; Lewis acid

• ; nucleoside; oligosaccharide; Introduction Nucleic acids and oligosaccharides are both mandatory polymers for the maintenance of life and cell growth. The former exists in nuclei and codes genetic information, which is transformed into proteins through a transcription process known as the “central dogma

Hyper-reticulated calixarene polymers: a new example of entirely synthetic nanosponge materials

• Alberto Spinella,
• Marco Russo,
• Antonella Di Vincenzo,
• Delia Chillura Martino and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2018, 14, 1498–1507, doi:10.3762/bjoc.14.127

• electrophiles such as epichlorohydrin [6], organic carbonates [7][8][9] or bis-isocyanates [10], in variable ratios depending on the required degree of reticulation. The process, of course, exploits the nucleophilic reactivity of the hydroxy groups of the macrocycle oligosaccharide unit. In general, CyNSs

Synthetic avenues towards a tetrasaccharide related to Streptococcus pneumonia of serotype 6A

• Aritra Chaudhury,
• Mana Mohan Mukherjee and
• Rina Ghosh

Beilstein J. Org. Chem. 2018, 14, 1095–1102, doi:10.3762/bjoc.14.95

• oligosaccharide synthesis. We have synthesized the aforesaid tetrasaccharide (SPn 6A) based on both stepwise and sequential one-pot glycosylation reactions using easily accessible common building blocks; eventually similar overall yields were obtained in both cases. Keywords: carbohydrates; glycosylation

Carbohydrate inhibitors of cholera toxin

• Vajinder Kumar and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2018, 14, 484–498, doi:10.3762/bjoc.14.34

• 0.5 r.m.s.) from exact rotational symmetry. Five long α-helices surround the central cylindrical pore through which the A2-subunit is threaded. Each subunit of a B-pentamer has a single binding site for the GM1 oligosaccharide on the face of the pentamer distal to the A1-subunit [12][14]. GM1 is a

• pocket. Both of these terminal sugar residues show hydrogen bonding interactions with the protein and associated water molecules. The GM1 oligosaccharide (GM1os) binds very tightly to CTB with a dissociation constant (Kd) of around 40 nM (measured by isothermal titration calorimetry, ITC), while simple

• the highest affinity site on the SLT-1 B-subunit has a Kd of only 1 mM [26], yet the toxin achieves sub-nanomolar affinity at a cell membrane. The purpose of the CTB blood group oligosaccharide binding site remains a topic for debate, but it may be responsible for the reported blood group dependence

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

• chloride (DMC), and related reagents, which can direct convert an oligosaccharide with a 2-acetamido sugar at the reducing terminus directly into the corresponding oxazoline in water. Therefore, oxazoline formation can now be achieved in water as the final step of any synthetic sequence, obviating the need

• protected (typically peracetylated) GlcNAc or other 2-acetamido sugar [37][38][39][40]. Oxazoline formation is achieved by activation of the leaving group at the anomeric centre and neighbouring group participation by the 2-acetamide. Unfortunately application of these reaction conditions to oligosaccharide

• substrates leads to significant cleavage of interglycosidic linkages, and correspondingly low yields of products. However, two methods that are useful for the production of oligosaccharide oxazolines are treatment of the peracetylated sugar with either TMSOTf in dichloroethane [39], or with TMSBr, BF3·Et2O

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

• micro-heterogeneous structure distinguished by three regions: the lipid A [5], the core oligosaccharide [6] and the O-antigen [7] (Figure 1B). The TLR4·MD-2 receptor complex senses picomolar amounts of LPS and initiates the biosynthesis of diverse mediators of inflammation (such as tumor necrosis factor

• 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

Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles

• Vivek Poonthiyil,
• Thisbe K. Lindhorst,
• Vladimir B. Golovko and
• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2

• many important biological processes, it is now well established that the binding interactions of a particular oligosaccharide, either with another carbohydrate or more commonly with carbohydrate-binding proteins (lectins), are generally weak. In order to augment these low affinity interactions

Solid-state studies and antioxidant properties of the γ-cyclodextrin·fisetin inclusion compound

• Joana M. Pais,
• Maria João Barroca,
• Maria Paula M. Marques,
• Filipe A. Almeida Paz and
• Susana S. Braga

Beilstein J. Org. Chem. 2017, 13, 2138–2145, doi:10.3762/bjoc.13.212

• , neuroprotecting, and suppression or prevention of tumors. The present work describes the preparation of a water-soluble, solid inclusion compound of fisetin with gamma-cyclodextrin (γ-CD), a cyclic oligosaccharide approved for human consumption. A detailed physicochemical analysis of the product is carried out

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

• protective group manipulation and aglycon adjustment often need to be performed on oligosaccharide intermediates, which lower the overall synthetic efficiency. Preactivation-based glycosylation refers to strategies where the glycosyl donor is activated by a promoter in the absence of an acceptor. The

• as sulfate esters and deoxy glycosides have been successfully synthesized. The preactivation-based chemoselective glycosylation is a powerful strategy for oligosaccharide assembly complementing the more traditional premixed method. Keywords: chemoselectivity; glycosides; preactivation; synthesis

• be coupled with another donor and this process is repeated until the desired oligosaccharide structure is assembled. Although many oligosaccharides have been successfully produced through this approach, the traditional oligosaccharide synthesis requires multiple synthetic manipulations on

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

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

• -glycosylation” by Valverde et al. [54], “remote glycosidation” by Takahashi [55] and “templated oligosaccharide synthesis” by Demchenko [56]. Initially introduced by Kusumoto et al. in 1986 [46], the molecular clamping clearly demonstrated the advantages that intramolecular glycosylations can offer. The first

• the phthaloyl clamping groups to present the oligosaccharide chain in a favorable conformation for cyclization. After hydrolyzing the anomeric protecting group, several conditions were tried to close the ring and glycosylation with the trichloroacetimidoyl leaving group in 23 activated with

• debenzylation followed by global acetylation to afford product 30. The extension of this approach to convergent oligosaccharide synthesis and reiterative sequencing in presented in Scheme 8. Thus, maltose and lactose disaccharide building blocks were linked via the xylylene tether, and the resulting compound 31

1,3-Dibromo-5,5-dimethylhydantoin as promoter for glycosylations using thioglycosides

• Fei-Fei Xu,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2017, 13, 1994–1998, doi:10.3762/bjoc.13.195

• agents that are commonly used in oligosaccharide synthesis due to their accessibility, stability, compatibility with various reaction conditions, and orthogonality to other donors [1][2][3][4][5]. Different electrophilic/thiophilic reagents have been developed as promoters to activate thioglycoside

Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C- and S-glycosides

• Jihen Ati,
• Pierre Lafite and
• Richard Daniellou

Beilstein J. Org. Chem. 2017, 13, 1857–1865, doi:10.3762/bjoc.13.180

• specific protecting and/or activating groups and the fine control of the resulting anomeric linkage, thus leading now to i) a huge repertoire of stereoselective methods for glycosylation reactions [3] and ii) the premise of few automated oligosaccharide synthesis [4], such glycosylation process still

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

• ) of glycosyl bonds [12]. Classical approaches in the transglycosylation of saccharides to form larger oligosaccharides utilize an endoglycosidase that couples a donor and an acceptor in situ to provide the lengthened oligosaccharide [13][14]. The primary challenge in transglycosylation strategies has

• furanosides. These may find application as enzyme substrates and possibly as inhibitors in several bacterial diseases, as well as in solid-phase-oligosaccharide synthesis, as shown. However, the main drawback is still the multistep synthesis of these anomeric activating donors. 3.2 Self-activation of the

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

• oligosaccharide acceptor and GDP lead to the understanding of the FUT1 mechanism [40]. Carbohydrate esterases: Carbohydrate esterases perform the de-O or de-N-acylation of carbohydrates. From a mechanistic point of view, this family of enzymes is divided into two classes, according to the dual role played by the

• thrombin and antithrombin at 2.5 Å resolution. For the time being, this is one of the largest oligosaccharide structures ever established throughout macromolecular X-ray crystallography (Figure 12) [59]. Transporters: Soluble sugars serve many purposes in complex organisms. Their cellular exchange relies

Urea–hydrogen peroxide prompted the selective and controlled oxidation of thioglycosides into sulfoxides and sulfones

• Adesh Kumar Singh,
• Varsha Tiwari,
• Kunj Bihari Mishra,
• Surabhi Gupta and
• Jeyakumar Kandasamy

Beilstein J. Org. Chem. 2017, 13, 1139–1144, doi:10.3762/bjoc.13.113

• role in carbohydrate synthesis. Thioglycosides, glycosyl sulfoxides and sulfones have been widely used as glycosyl donors in oligosaccharide synthesis which can be activated under mild reaction conditions [5][6][7][8][9][10]. Glycosyl sulfoxide donors usually provide excellent anomeric selectivity

• during the synthesis of various glycosyl linkages not only in solution phase but also in solid-phase oligosaccharide synthesis [6][7][8][9][11]. Glycosyl sulfones were also used as donors in the preparation of various C- and O- linked oligosaccharides and functionalized glycols [8][9][12]. In addition

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

• on the identification of sugar epitopes of the surface envelope glycoprotein of HIV-1, capable of eliciting a protective response. GAuNPs coated with high-mannose type oligosaccharide of HIV-1 gp120, were prepared as glycoconjugate systems able to mimic the natural presentation of gp-120 high-mannose

• [105]. In another recent study on the development of synthetic nanosystems as potential carbohydrate-based vaccine, GAuNPs were loaded with synthetic oligosaccharide fragments corresponding to the repeating units of S. pneumoniae (Pn) CPS type 19F and 14 [106]. This new approach has explored the effect

Structure–efficiency relationships of cyclodextrin scavengers in the hydrolytic degradation of organophosphorus compounds

• Sophie Letort,
• Michaël Bosco,
• Benedetta Cornelio,
• Frédérique Brégier,
• Sébastien Daulon,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2017, 13, 417–427, doi:10.3762/bjoc.13.45

• TRIMEB didn’t affect the degradation of the pesticide compared to IBA alone. The influence of the intermolecular interactions between the pesticides and the methylated oligosaccharide is of fundamental importance towards the degradation process. The degradation efficiency of IBA and compounds 1 and 4

• iodosobenzoate group and the methylated oligosaccharide; (4) in case of soman, the degradation is enhanced by a cooperative effect observed between the imidazole and 2-iodosobenzoate when the latter is in close proximity to the macrocycle. A more extended structure–activity relationship study is envisaged to

Total synthesis of a Streptococcus pneumoniae serotype 12F CPS repeating unit hexasaccharide

• Peter H. Seeberger,
• Claney L. Pereira and
• Subramanian Govindan

Beilstein J. Org. Chem. 2017, 13, 164–173, doi:10.3762/bjoc.13.19

• + 3] total synthesis approach prompted us to retreat to the linear avenue (Scheme 1, route B) towards the target oligosaccharide in order to avoid the sterically demanding late-stage glycosylation. Differentially protected mannosazide 4 served as the starting point for stepwise assembly from the

• approach. A convergent [3 + 3] total synthesis strategy failed, most likely due to steric crowding around the trisaccharide acceptor. The synthesis of 1 is an illustrative example of the challenges associated with state-of-the-art oligosaccharide assembly including steric, conformational, remote

Silyl-protective groups influencing the reactivity and selectivity in glycosylations

• Mikael Bols and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2017, 13, 93–105, doi:10.3762/bjoc.13.12

• provide an alternative orthogonal protective group to the more conventional acetyl, benzoyl and benzyl groups. Particularly in oligosaccharide synthesis where many orthogonal hydroxy protective groups are required silicon protective groups have frequently been introduced in both glycosyl donors and

• benzoylated thioglycosides with high chemoselectivity and was therefore used in a range of high yielding oligosaccharide syntheses [38]. The bifunctional silicon protective group DTBS (Figure 1) has been used both to increase and decrease the reactivity of glycosyl donors. The 4,6-O-DTBS-protected

Synthesis and NMR studies of malonyl-linked glycoconjugates of N-(2-aminoethyl)glycine. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger,
• Sven Hafner and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 1939–1948, doi:10.3762/bjoc.12.183

• , on the other hand, may provide sufficient amounts of pure material for such studies. Despite the great achievements in oligosaccharide synthesis during the past decades, the preparation of complex oligosaccharides can be tedious, lengthy or circuitous, and the often intrinsic intricacy of a chemical

• saccharide synthesis makes it sometimes impossible to prepare a certain saccharide or glycoconjugate [9]. Therefore, gaining access to new glycoconjugates which are easily accessible by chemical synthesis and which are able to mimic the interaction between a specific protein and its natural oligosaccharide

TMSBr-mediated solvent- and work-up-free synthesis of α-2-deoxyglycosides from glycals

• Mei-Yuan Hsu,
• Yi-Pei Liu,
• Sarah Lam,
• Su-Ching Lin and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2016, 12, 1758–1764, doi:10.3762/bjoc.12.164

• exclusively when the secondary hydroxyl glucoside 24 was used (Table 4, entry 13). Notably, the disubstituted side product was not observed in this reaction. On the basis of these results, we demonstrated the applicability of the methodology in oligosaccharide synthesis by synthesising trisaccharide 66 in two

Automated glycan assembly of a S. pneumoniae serotype 3 CPS antigen

• Markus W. Weishaupt,
• Stefan Matthies,
• Mattan Hurevich,
• Claney L. Pereira,
• Heung Sik Hahm and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2016, 12, 1440–1446, doi:10.3762/bjoc.12.139

• oligosaccharide mixture of different chain lengths and frame shifts. Access to defined synthetic S. pneumoniae CPS structures is desirable. Known syntheses of S. pneumoniae serotype 3 CPS rely on a time-consuming and low-yielding late-stage oxidation step, or use disaccharide building blocks which limits

• variability. Herein, we report the first iterative automated glycan assembly (AGA) of a conjugation-ready S. pneumoniae serotype 3 CPS trisaccharide. This oligosaccharide was assembled using a novel glucuronic acid building block to circumvent the need for a late-stage oxidation. The introduction of a washing

• containing oligosaccharides of different lengths and frame shifts [19]. Synthetic oligosaccharide antigens enable structure–activity relationship (SAR) studies of bacterial antigens [20] to better understand antibody binding and help to improve existing vaccine formulations. Two synthetic routes to prepare

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

• , 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

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-azido-hexopyranoses have potential as synthons in oligosaccharide assembly. Keywords: amino sugars; cytotoxicity; fluorinated carbohydrates; fluorine; hexosamines; Introduction Derivatives of D-glucosamine (GlcN) and D-galactosamine (GalN) are essential amino sugar components of glycans in

Elucidation of a masked repeating structure of the O-specific polysaccharide of the halotolerant soil bacteria Azospirillum halopraeferens Au4

• Elena N. Sigida,
• Yuliya P. Fedonenko,
• Alexander S. Shashkov,
• Nikolay P. Arbatsky,
• Evelina L. Zdorovenko,
• Svetlana A. Konnova,
• Vladimir V. Ignatov and
• Yuriy A. Knirel

Beilstein J. Org. Chem. 2016, 12, 636–642, doi:10.3762/bjoc.12.62

• revealed that its reason is a non-stoichiometric side-chain glucosylation and methylation of the main polysaccharide chain but at this stage, a straightforward structure elucidation of the OPS by NMR spectroscopy [16] was complicated. In order to obtain oligosaccharide fragments of the OPS a Smith

• oligosaccharide, selective solvolysis with CF3CO2H was employed. Recently, this method has been successfully used for the structure elucidation of the O-specific polysaccharides of Escherichia coli (e.g. [20]). The reagent was found to cleave selectively the glycosidic linkage of 6-deoxyhexoses (Rha, Fuc

• indicated that the degree of O-methylation was ca. 45% and the degree of side-chain glucosylation was ca. 65%. Conclusion Based on the chemical and NMR spectroscopic data, it was concluded that the OPS of A. halopraeferens Au4 has a masked repeating structure and consists of four types of oligosaccharide