Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• modifications which have been undertaken on the nicotinoyl riboside scaffold. Keywords: anomers; glycosylation; isotopologues; isotopomeres; nicotinamide riboside; Review 1. Introduction 1-(β-D-Ribofuranosyl)nicotinamide (also referred to as nicotinamide riboside, NR+) is one of the multiple precursors of

• applicability, while most interesting developments in terms of synthetic efficiency, improved stereoselectivity and overall yields relate to the first approach. This approach, the synthetic glycosylation conditions depend on the nature of the sugar component. These conditions differ whether 1-halo-2,3,5-tri-O

• -acyl- or 1,2,3,5-tetra-O-acyl-D-ribofuranose is used, as fully acylated ribofuranoses require the usage of Friedel–Crafts catalysts to be activated as glycosylation reagents. As it is shown in Figure 2, reactions between compounds A and B may result in two anomeric α- and β-forms of nicotinamide

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• and D-glucuronic acid (GlcA) acceptors. These results, together with those obtained from experiments employing model monosaccharide building blocks, highlight the impact of the glycosyl acceptor structure on the stereoselectivity of glycosylation reactions. Our study provides useful data about the

• substitution pattern of GlcA units for the efficient synthesis of CS oligomers. Keywords: carbohydrate chemistry; chondroitin sulfate; glycosylation; oligosaccharide synthesis; stereoselectivity; Introduction Chondroitin sulfate (CS) is a highly heterogeneous polysaccharide, constituted by the repetition of

• coupling between N-acetyl building blocks with the opposite sequence GalNAc-GlcA [16][17][18][19]. All of these routes involved the use of low reactive glucuronic acid moieties in glycosylation reactions. Very recently, a postglycosylation–oxidation strategy was applied to the synthesis of CS type E

Synthesis of α-D-GalpN₃-(1-3)-D-GalpN₃: α- and 3-O-selectivity using 3,4-diol acceptors

• Emil Glibstrup and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2018, 14, 2805–2811, doi:10.3762/bjoc.14.258

• azido precursor has been studied and optimized in terms of steps, yields and selectivity. It has been found that glycosylation of the 3,4-diol acceptor is an advantage over the use of a 4-O-protected acceptor and that both regio- and anomeric selectivity is enhanced by bulky 6-O-protective groups. The

• acceptors and donors are made from common building blocks, limiting protective manipulations, and in this context, unavoidable side reactions. Keywords: diastereoselectivity; glycosylation; regioselectivity; Introduction The disaccharide α-D-GalpNAc-(1-3)-β-D-GalpNAc is a widespread motif in glycobiology

• finding important for oligosaccharide synthesis. Here we describe this regioselective glycosylation approach in detail. Results and Discussion In the initial strategy for synthesizing the disaccharide, the fully protected acceptor (1 or 2) was intended to be a key building block. However, an unexpected

Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues

• Kai Zhang,
• Jiarong Li,
• Honglin Liu,
• Haiyou Wang and
• Lamusi A

Beilstein J. Org. Chem. 2018, 14, 2321–2330, doi:10.3762/bjoc.14.207

• as the glycosylation donor of C9–OH, but also the protecting group of C17–OH, greatly reducing the synthetic steps and costs. Macrolide compounds are a new kind of insecticides and fungicides which have also been widely applied in medicine [14][15]. Currently, research on structural modification of

• BF3·(C2H5)2O under Ar gas. Due to the high yields and few byproducts in the synthesis of glycoside donors, the donors could be used directly in the glycosylation without purification. Insecticidal activity The insecticidal activities of synthetic spinetoram J and its analogues were evaluated using

Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as inhibitors of GH38 α-mannosidases

• Maroš Bella,
• Sergej Šesták,
• Ján Moncoľ,
• Miroslav Koóš and
• Monika Poláková

Beilstein J. Org. Chem. 2018, 14, 2156–2162, doi:10.3762/bjoc.14.189

• swainsonine, interferes with the glycosylation pathway where it specifically inhibits GH38 glycoside hydrolases [23][24]. Up to date, swainsonine is the most potent Golgi mannosidase II (GMII) inhibitor. It is known that inhibition of the biosynthesis of complex N-glycans in the Golgi apparatus influences

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

• is hindered. In the literature this fact is used to explain the different reactivities between “armed” and “disarmed” glycosyl donors in glycosylation reactions [33]. Due to the fact that 9 can be attacked from two sides by nitriles, the oxazolines occur in two isomeric forms, the β-anomers (10) and

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• to be either converted into glycosides or into other anomerically modified carbohydrate derivatives. We intend to provide a critical survey as well as a source of inspiration, even more so as glycosylation remains a challenge in carbohydrate chemistry. Review Mechanistic considerations Since

• carbocyclic lignan variants related to podophyllotoxin, a pseudo-anomeric stereospecific inversion of a carbasugar was achieved in good yield in Nishimura’s group [39]. More recently, the Mitsunobu procedure was applied in the context of gold-catalyzed glycosylation in order to install a reactive anomeric

• phenols to achieve aryl glycosides Not only anomeric esters, but also glycosides can be obtained through the Mitsunobu reaction. Dehydrative glycosylation approaches with reducing sugars were previously reviewed [43][44]. As phenols are weak acids, they are suitable reaction partners in the Mitsunobu

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

• donor of in the latter are carried out in the presence of an appropriate activator. As an activator of the glycosylation, a combination of a Lewis acid catalyst and a hypervalent iodine was developed for synthesizing 4’-thionucleosides, which could be applied for the synthesis of 4’-selenonucleosides as

• well. The extension of hypervalent iodine-mediated glycosylation allowed us to couple a nucleobase with cyclic allylsilanes and glycal derivatives to yield carbocyclic nucleosides and 2’,3’-unsaturated nucleosides, respectively. In addition, the combination of hypervalent iodine and Lewis acid could be

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

• sequential glycosylation strategies. Results and Discussion Keeping in mind our objective to synthesize the SPn 6A tetrasaccharide following stepwise as well as one-pot synthetic strategies based on common building blocks, a retrosynthetic analysis was made which led us to galactose-based donor 2 [26

• order to construct the central disaccharide fragment 3 in high yield with 1,2-cis selectivity, several glycosylation reactions using glucosyl donors 6a/6b/6c/12a and rhamnosyl acceptor 5 were contemplated. None of the conditions, based on the use of thioglycoside 6a as the glycosyl donor and separately

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

• -benzoylated disaccharides needed 2–3 h of heating at 55 °C. Keywords: acylated sugars; azidation; gold(III) bromide; N-glycoside; oxophilicity; Introduction The past few decades had seen the enrichment of transition metal complexes in various glycosylation strategies [1]. In particular, gold complexes with

• their operationally simple, safe and neutral reaction conditions, had widely contributed to the development of new glycosylation methods. Gold(I) and gold(III) complexes are usually alkynophilic [2], carbophilic and oxophilic because of their affinity towards the alkynes’ and C–O π systems [3][4][5][6

• ]. Thus, various research groups employed either a remote alkyne group possessing versatile glycosyl donors [7][8][9][10][11][12][13][14][15][16] or used glycals [17] for effective O-, C-, and S-glycosylation reactions using gold(I) and gold(III) catalysts. Among the gold-catalyzed activation of non

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

• synthetic approaches reported, the majority rely on the fabrication (either by total synthesis, or semi-synthesis from locust bean gum) of a key Manβ(1–4)GlcNAc disaccharide, which can then be elaborated at the 3- and 6-positions of the mannose unit using standard glycosylation chemistry. Early approaches

• 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

• be optimal. An example that employed these key steps was used to synthesise a truncated complex biantennary N-glycan oxazoline [62], as shown in Scheme 4. Following the gluco to manno epimerisation process, selective deprotection of OH-3 of the mannose unit was followed by glycosylation and extension

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• glycosylation using the sodium-salt method as later also performed in the synthesis of tCnitro in 2009 (reaction c, Scheme 3) [14][42]. The synthesis was finished by standard DMTr protection and phosphitylation furnishing tC deoxyribose phosphoramidite in a total of 2.1% yield over 6 steps [43][44]. In 2008

• where the acid-catalyzed cyclization as well as the glycosylation proved challenging. The latter two steps proceeded with a yield of 15% or less (17, Scheme 3). A new synthetic approach to access substituted tricyclic cytosines was envisioned in 2014 by Rodgers et al. (Scheme 4). This protocol increased

• the yield of the parent compound tC from 10% up to 43% in the glycosylation step of the previously prepared tC nucleobase (Scheme 4) [47]. This was achieved by activation of the aromatic core of compounds 18a–c via trimethylsilylation using BSA (bis(trimethylsilyl)acetamide) [47], instead of the

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

• double glycosyl phosphodiesters. Keywords: glycoconjugate; glycolipids; glycosylation; immunomodulation; lipopolysaccharide; TLR4; Introduction The mammalian innate immune system possesses an efficient and incredibly complex evolutionary ancient machinery responsible for host defence against pathogens

• seemingly simple transformations needed for the assembly of lipid A, such as glycosylation towards fully orthogonally protected β(1→6)-linked diglucosamine backbone, sequential protective groups manipulation combined with successive instalment of multiple functional groups, N- and O-acylation with the long

• reductive opening of benzylidene acetal using the borane−THF complex in the presence of Bu2BOTf. Regioselective TMSOTf-catalysed glycosylation of the diol 4 by the imidate donor 3 resulted in the formation of a single product, the β(1→6)-linked disaccharide 5. After the 2’-N-Fmoc group in 5 was removed with

Position-dependent impact of hexafluoroleucine and trifluoroisoleucine on protease digestion

• Susanne Huhmann,
• Anne-Katrin Stegemann,
• Kristin Folmert,
• Damian Klemczak,
• Johann Moschner,
• Michelle Kube and
• Beate Koksch

Beilstein J. Org. Chem. 2017, 13, 2869–2882, doi:10.3762/bjoc.13.279

• assay [30]. Substitution of tryptophan, tyrosine, and phenylalanine residues in a glycosylation-deficient mutant of Candida antarctica lipase B, CalB N74D, by their monofluorinated analogues, left the resistance to proteolytic degradation by proteinase K unchanged [31]. Incorporation of α-fluoroalkyl

A semisynthesis of 3'-O-ethyl-5,6-dihydrospinosyn J based on the spinosyn A aglycone

• Kai Zhang,
• Shenglan Liu,
• Anjun Liu,
• Hongxin Chai,
• Jiarong Li and
• Lamusi A

Beilstein J. Org. Chem. 2017, 13, 2603–2609, doi:10.3762/bjoc.13.257

• ][20][21][22], but there are few studies on the chemical synthesis of 3'-O-ethyl-5,6-dihydrospinosyn J. Considering the high fermentation productivity and low cost of spinosyn A, we designed a semi-synthesis of 3'-O-ethyl-5,6-dihydrospinosyn J from the spinosyn A aglycone via sequential glycosylation

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• to 1.7 nM for glycosylated gp120 (25 glycosylation sites) [43][77]. In the case of UPEC, each bacterium contains three to five hundred fimbriae to potentiate multivalency, as each FimHLD (I) at the fimbrial tip can interact with mammalian UPIa [78]. Multivalent glycosides have also been investigated

Electron-deficient pyridinium salts/thiourea cooperative catalyzed O-glycosylation via activation of O-glycosyl trichloroacetimidate donors

• Mukta Shaw,
• Yogesh Kumar,
• Rima Thakur and
• Amit Kumar

Beilstein J. Org. Chem. 2017, 13, 2385–2395, doi:10.3762/bjoc.13.236

• Mukta Shaw Yogesh Kumar Rima Thakur Amit Kumar Department of Chemistry, Indian Institute of Technology Patna, Bihta 801106, Bihar, India Department of Chemistry, National Institute of Technology Patna, Patna 800005, Bihar, India 10.3762/bjoc.13.236 Abstract The glycosylation of O-glycosyl

• , the optimized method is also utilized for the regioselective O-glycosylation by using a partially protected acceptor. Keywords: cooperative catalysis; electron-deficient pyridinium salts; O-glycoside; regioselectivity; thiourea; Introduction The glycosidic linkage is the principal bond present in a

• crucial class of biomolecules such as oligosaccharides and glycoconjugates, where one sugar unit is linked with another sugar unit or any other molecules (aglycons) [1][2][3][4]. Owing to their high importance, several efficient protocols have been developed for the stereoselective glycosylation in 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

• the obtained compounds are active against Gram-positive bacteria and Candida type fungi. Keywords: antimicrobial activities; D-galactosamine; diosgenin; glycosylation; saponin; tetrachlorophthalimido derivatives; Introduction Saponins are steroid or triterpenoid glycosides found in various plants [1

• in the glycosylation. This mixture of 2 is chromatographically inseparable due to the highly reactive nature of the bromine group at the anomeric carbon, but, the anomers of 2 are readily distinguishable in the NMR spectrum (δ 6.65, d, J1,2 = 3.7 Hz for the α anomer and δ 6.35, d, J1,2 = 9.6 Hz for

• the β anomer). Glycosylation of diosgenin with 2 was performed in dichloromethane by a “reverse” procedure: The glycosyl donor was added to the solution of diosgenin and the promoter (silver triflate) [31]. This procedure afforded the expected β glycoside 3 in 80% yield. The structure of 3 was

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

• University, East Lansing, MI 48824, USA 10.3762/bjoc.13.207 Abstract Most glycosylation reactions are performed by mixing the glycosyl donor and acceptor together followed by the addition of a promoter. While many oligosaccharides have been synthesized successfully using this premixed strategy, extensive

• 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

• subsequent acceptor addition then leads to the formation of the glycoside product. As donor activation and glycosylation are carried out in two distinct steps, unique chemoselectivities can be obtained. Successful glycosylation can be performed independent of anomeric reactivities of the building blocks. In

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

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

• for elaborate protecting and leaving group manipulations, functionalization, tedious purification, and sophisticated characterization. Achieving high stereocontrol in glycosylation reactions is arguably the major hurdle that chemists experience. This review article overviews methods for intramolecular

• glycosylation reactions wherein the facial stereoselectivity is achieved by tethering of the glycosyl donor and acceptor counterparts. Keywords: carbohydrates; glycosylation; intramolecular reactions; oligosaccharides; Introduction With recent advances in glycomics [1][2], we now know that half of the

• proteins in the human body are glycosylated [3], and cells display a multitude of glycostructures [4]. Since glycan and glycoconjugate biomarkers are present in all body fluids, they offer a fantastic opportunity for diagnostics. Changes in the level of glycans, as well as changes in glycosylation and

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

• trimethylsilyl trifluoromethanesulfonate (TMSOTf) were employed as co-promoters in solution or automated glycan assembly on solid phase. Keywords: automated glycan assembly; 1,3-dibromo-5,5-dimethylhydantoin; glycosylation; promoter; thioglycosides; Introduction Thioglycosides are versatile glycosylating

• of their aglycons (SEt or STol). This promoter is compatible with most commonly used protecting groups, except some electron-rich groups like 4-methoxybenzyl ethers that may be partly brominated under these conditions [40]. To probe the scope of DBDMH/TfOH-mediated 1,2-cis-glycosylation

• stereoselectivity of the reactions follows reported trends. This promoter system was successfully used for automated glycan assembly. DBDMH as promotor for automated glycan assembly. Modules: a) acidic wash; b) glycosylation using DBDMH/TMSOTf, 8; c) Fmoc deprotection. Hydrolysis of glycosyl selenide 17 with DBDMH

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

• thought to represent powerful and greener alternatives to conventional chemical glycosylation procedures. The knowledge of their corresponding mechanisms has already allowed the development of efficient biocatalysed syntheses of complex O-glycosides. These enzymes can also now be applied to the formation

• 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

• . Glycoside hydrolases (GHs) or glycosyltransferases (GTs) have been focused on in the search for glycosylation tools, and have been extensively studied for genetic engineering [9][10]. The corresponding compounds have proven useful in many applications ranging from glycosylation of natural products to

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

• Abstract Glycosylation is an immensely important biological process and one that is highly controlled and very efficient in nature. However, in a chemical laboratory the process is much more challenging and usually requires the extensive use of protecting groups to squelch reactivity at undesired reactive

• review, we showcase the methods available for the selective activation of the anomeric center on the glycosyl donor and the mechanisms by which the glycosylation reactions take place to illustrate the power these techniques. Keywords: glycosides; glycosylation; oligosaccharides; protecting groups

• ; Review 1 Introduction The glycosylation reaction is of extreme importance in nature as it is possibly the most prevalent post-translational modification and thus has implications in a tremendous number of biological processes, including diseases [1]. More expedient chemical and enzymatic methods to

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

• family of glycosylated proteins with a high molecular weight, produced by epithelial tissues. The most studied is the membrane-bound glycoprotein MUC1, a glycoprotein with extensive O-linked glycosylation in its extracellular domain. The authors demonstrated that the multivalent presentation of MUC1

Total synthesis of TMG-chitotriomycin based on an automated electrochemical assembly of a disaccharide building block

• Yuta Isoda,
• Norihiko Sasaki,
• Kei Kitamura,
• Shuji Takahashi,
• Sujit Manmode,
• Naoko Takeda-Okuda,
• Jun-ichi Tamura,
• Toshiki Nokami and
• Toshiyuki Itoh

Beilstein J. Org. Chem. 2017, 13, 919–924, doi:10.3762/bjoc.13.93

• electrochemical solution-phase synthesis developed by us. The synthesis of structurally well-defined TMG-chitotriomycin has been accomplished in 10-steps from a disaccharide building block. Keywords: automated synthesis; electrochemical oxidation; glycosylation; glucosamine; total synthesis; Introduction

• ) stereoselectively, we initiated our study by optimization of the reaction conditions of the first glycosylation using 2-deoxy-2-azidothioglycoside 2 as a glycosyl donor. The azido group at the C2-position is a well-known substituent, which facilitates the formation of an α-glycosidic linkage selectively due to the

• an equilibrium between the α-isomer and the β-isomer of 3a. To the contrary, glycosyl triflate 3b, derived from thioglycoside 2b, might be more reactive and affords the β-product 5bβ before isomerization from the α-isomer 3bα to the β-isomer 3bβ. In this case, glycosylation via 3bα becomes the major