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

Expression, purification and structural analysis of functional GABA transporter 1 using the baculovirus expression system

• Jing Hu,
• Chris Weise,
• Christoph Böttcher,
• Hua Fan and
• Jian Yin

Beilstein J. Org. Chem. 2017, 13, 874–882, doi:10.3762/bjoc.13.88

• GAT1 demonstrates that this single polypeptide contains twelve TM domains connected by hydrophilic loops with the amino and carboxy-termini residing in the cytoplasm [9][10]. Additionally, the GAT1 protein contains three conserved N-glycosylation sites [9]. The role of N-linked glycans in the GABA

• -glycosylation status. After 30 years of development, the baculovirus expression system has become a widely applied technology for producing recombinant proteins [30][31]. Since the production of adequate quantities of a homogenous protein is a rate-limiting step, in this study, we chose the baculovirus

• expressed in the baculovirus expression system. The results showed that infected Sf9 cells (0.15 pmol/106 cells) have only slightly higher GABA uptake activity than mock cells (0.1 pmol/106 cells) (Figure S3, Supporting Information File 1). A previous work demonstrated that co-translational N-glycosylation

First total synthesis of kipukasin A

• Chuang Li,
• Haixin Ding,
• Zhizhong Ruan,
• Yirong Zhou and
• Qiang Xiao

Beilstein J. Org. Chem. 2017, 13, 855–862, doi:10.3762/bjoc.13.86

• subsequent Vorbrüggen glycosylation, the protecting group could be removed smoothly in the presence of 5 mol % Ph3PAuOTf in dichloromethane to provide kipukasin A in high yield and regioselectivity. Keywords: gold catalysis; kipukasin A; marine nucleoside; total synthesis; Vorbrüggen glycosylation

• ). Kipukasin A could be constructed by Vorbrüggen glycosylation [22][23] of a properly protected glycosyl donor 3 with uracil (4). Neighboring group participation of the 2’-O-acetyl group stereoselectively facilitate the β-glycosidic bond formation. Thus, the choice of a suitable protecting group at 5-OH

• position would be crucial for the success. It should fulfill at least two requirements: (1) it should be stable during the Vorbrüggen glycosylation; and (2) the deprotection process should be performed under very mild and neutral conditions without any influence on the 2’-O-acetyl group. At the same time

Synthesis of ribavirin 2’-Me-C-nucleoside analogues

• Fanny Cosson,
• Aline Faroux,
• Jean-Pierre Baltaze,
• Jonathan Farjon,
• Régis Guillot,
• Jacques Uziel and
• Nadège Lubin-Germain

Beilstein J. Org. Chem. 2017, 13, 755–761, doi:10.3762/bjoc.13.74

• the combination, due to its particular role. Recently, we developed an alkynyl glycosylation protocol allowing us to obtain C-nucleoside derivatives and we turned our attention to ribavirin C-nucleoside analogues. Moreover, recently De Clerq [13] outlined the potential of C-nucleosides in the arsenal

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

• ] strategy that was not successful due to steric constraints. The synthetic hexasaccharide is the starting point for further immunological investigations. Keywords: carbohydrate antigen; glycosylation; oligosaccharides; Streptococcus pneumoniae; total synthesis; Introduction Streptococcus pneumoniae is a

• glycosylation of the liberated hydroxy groups. Formation of the β-mannosazide glycoside containing a protected C5 amino linker that serves in the final product as an attachment point for glycan array surfaces or carrier proteins was central to the assembly of trisaccharide 3. To avoid a challenging and often

• [25]. Silylation of the C3 hydroxy group furnished thioglycoside 17. Glycosylation of the C5 linker by activation of 17 using NIS/TfOH as the promoter at −20 °C produced mainly β-mannoside 15 (4:1 β:α) [26]. The identity of the β-isomer was confirmed by NMR analysis (1JCH β = 159.0 Hz, see Supporting

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

• or high stereoselectivity. This mini review will summarize these findings. Keywords: Carbohydrate; conformation; glycosylation; reactivity; selectivity; Introduction Silicon-based protective groups of alcohols have a long history in organic chemistry [1][2][3]. The most popular and commercially

• acceptors. However, glycosylation with heavily silylated carbohydrate derivatives is comparatively new, and so is the significance that silyl groups have on the stereoselectivity and reactivity in glycosylation reactions [4]. These findings, which most have occurred in the last decade, will be reviewed here

• protective groups on the donor a TES-protected trichloroacetimidate of fucose, 4, was employed by Myers et al. [7] in order to have protective groups compatible with their synthesis of neocarzinostatin. It was found that optimal glycosylation was performed with TMSOTf as a catalyst at low temperature and

O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside

• Roman Sommer,
• Dirk Hauck,
• Annabelle Varrot,
• Anne Imberty,
• Markus Künzler and
• Alexander Titz

Beilstein J. Org. Chem. 2016, 12, 2828–2833, doi:10.3762/bjoc.12.282

• derivatives are nowadays used as powerful tools in organic chemistry [6]. Synthetic selenoglycosides are versatile synthons in glycosylation reactions as glycosyl donors for the synthesis of glycosides and oligosaccharides, where their aglycon acts as a leaving group [7][8][9]. They can be selectively

• activated due to their enhanced reactivity in the presence of other chalcogen-containing glycosides such as O- or S-glycosides. By exploiting these properties, one-pot multi-step glycosylation reactions have been developed recently [10][11]. Natural selenosugars, such as methylseleno N-acetyl-β-D

• Fischer-type glycosylation and pure allyl α-fucoside (7) was obtained after crystallization in 43% yield (Scheme 2). Selective protection of the 3,4-cis-diol as an acetonide followed by methylation of the hydroxy group in position 2 yielded derivative 8 in 85% yield over two steps. Then, the acetonide

Enzymatic synthesis and phosphorolysis of 4(2)-thioxo- and 6(5)-azapyrimidine nucleosides by E. coli nucleoside phosphorylases

• Vladimir A. Stepchenko,
• Anatoly I. Miroshnikov,
• Frank Seela and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2016, 12, 2588–2601, doi:10.3762/bjoc.12.254

• only 5-phenyl- and 5-tert-butyl-6-azauracils displayed very low substrate activity. The role of structural peculiarities and electronic properties in the substrate recognition by E. coli nucleoside phosphorylases is discussed. Keywords: enzymatic glycosylation; PM3 and ab initio calculations

• extract of Streptococcus faecalis as biocatalysts [26]. Later on, the conversion of 6-azapyrimidines into their ribonucleosides was observed during the cultivation of Streptococcus faecalis [27][28] and E. coli [29] cells, as well as an enzymatic glycosylation of 14C-labeled 6-azapyrimidines employing the

• '-deoxyriboside 4SUd (Figure 2). The inertness of 2SUra towards glycosylation catalyzed by both UP and TP was surprising in the light of the works of Kalckar and Friedkin which studied TP from horse liver [1][32][33][34]. Moreover, Hatano et al. [35] briefly described a very efficient conversion of 2-thiouracil

Facile synthesis of a 3-deazaadenosine phosphoramidite for RNA solid-phase synthesis

• Elisabeth Mairhofer,
• Elisabeth Fuchs and
• Ronald Micura

Beilstein J. Org. Chem. 2016, 12, 2556–2562, doi:10.3762/bjoc.12.250

• ). Then, glycosylation with 1-O-acetyl-2,3,5-tri-O-benzoyl-ß-D-ribofuranose gave the desired nucleoside 2 in high yield. Unfortunately, all our attempts to find appropriate conditions to reduce the 6-azido group to the corresponding amine failed. In short, these trials included i) hydrogenation under Pd/C

Inhibition of peptide aggregation by means of enzymatic phosphorylation

• Kristin Folmert,
• Malgorzata Broncel,
• Hans v. Berlepsch,
• Christopher H. Ullrich,
• Mary-Ann Siegert and
• Beate Koksch

Beilstein J. Org. Chem. 2016, 12, 2462–2470, doi:10.3762/bjoc.12.240

• characteristics, outstanding stability, regular fibrous architecture and high synthetic accessibility with numerous chemoselective ligation and modification methods [24][25][26]. Also, various post-translational modifications, like phosphorylation or glycosylation have been studied as aggregation triggers [27][28

The weight of flash chromatography: A tool to predict its mass intensity from thin-layer chromatography

• Freddy Pessel,
• Jacques Augé,
• Isabelle Billault and
• Marie-Christine Scherrmann

Beilstein J. Org. Chem. 2016, 12, 2351–2357, doi:10.3762/bjoc.12.228

• with a particularly low MIChr, compared to the other examples, corresponded to a filtration on silica gel rather than to a flash chromatography. The last example (Scheme 1d) is a S-glycosylation (isolated yield = 62%) leading to compound 4 [20]. For this crude reaction mixture containing 61% of 4, a

Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

• Pramod R. Markad,
• Navanath Kumbhar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2016, 12, 1765–1771, doi:10.3762/bjoc.12.165

• the formation of the pyranose ring skeleton to give 2,7-dioxabicyclo[3.2.1]octane 12. Functional group manipulation in 12 gave 21 that on stereoselective β-glycosylation afforded the pyranosyl thymine nucleoside 2 – a core of amipurimycin. Keywords: amipurimycin; 1,3-anhydrosugar; anti-fungal agent

• -acetylamino)-6-chloropurine 17, under a variety of reaction conditions, of solvents, temperature, Lewis acids as well as the use of the thymine nucleobase 18 (Scheme 4) failed to provide the desired nucleoside. Knowing the fact that the glycosylation reaction is severely influenced by numerous factors

• including solvent, Lewis acid, and protecting groups on the nucleobase or sugar; we thought of synthesizing the peracylated anhydrosugar to alter its reactivity towards glycosylation [22]. In this regard, anhydrosugar 15 was subjected to 10% Pd/C and Et3SiH (for deprotection of the benzyl functionality and

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

• functionalities at C6 [10][38][39][40][41][42] have also been developed to improve the stereoselectivity. However, additional required steps involving the introduction and removal of directing groups are reducing the efficiency. Thioglycosides are some of the most commonly used donors for glycosylation reactions

• the aforementioned methods. Furthermore, organic solvents in laboratories are associated with numerous health hazards [64], and most of them are consumed during chemical reactions, work-up and purification procedures. Especially, dichloromethane, one of the most general solvents for glycosylation

• reactions, is acknowledged as an acute inhalation hazard and carcinogen [65][66]. To date, only a few studies of glycosylation under neat conditions have been published. In these methods either the need of heating [67][68][69] or the use of ball milling [70][71][72] was demanded. Moreover, the selectivity

Organic chemistry meets polymers, nanoscience, therapeutics and diagnostics

• Vincent M. Rotello

Beilstein J. Org. Chem. 2016, 12, 1638–1646, doi:10.3762/bjoc.12.161

• equally importantly identify if the therapeutic acted by a mechanism novel to the training set. The capabilities of this sensor are quite impressive, but you may ask "what is it on the cell surface that the sensor is responding too?" We have an excellent clue to that question: changes in glycosylation

• (through mutation or glycolosis) generate very strong sensor responses, implicating that our sensor responds to changes in glycosylation [86] which is probably also the mechanism in play for our successful determination of biofilms using this platform [87]. Whither next? You can probably tell from the

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• )-hexofuranose (2) was obtained in good yield from 1,2,5-tri-O-acetyl-3-O-benzoyl-6-deoxy-6-diethylphosphono-(α,β)-ribo-(5S)-hexofuranose [15] following a glycosylation procedure using sodium azide as nucleophilic entity and tin(IV) chloride as Lewis acid. Under these conditions, the reaction appeared highly

• compound isolated from the glycosylation reaction corresponds to a single anomer as only one signal for the anomeric proton was detectable in the 1H NMR spectra. The beta-configuration of the azido-sugar-phosphonate intermediate 2 was established on the basis of the 1H,1H NMR spectra showing a cross-peak

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

• step with the activator prior to each glycosylation cycle greatly increased the yields by neutralizing any residual base from deprotection steps in the synthetic cycle. This process improvement is applicable to AGA of many other oligosaccharides. Keywords: automation; glycosylation; protecting groups

• ]. The building blocks were synthesized in high yields using standard protecting group chemistry (see Supporting Information File 1). Solid support 4 was prepared according to an established procedure [28]. The automated glycosylation protocol employed three times three equivalents of building block to

• ensure complete glycosylation of the nucleophile (Scheme 1). The glycosyl phosphate building blocks 1 and 2 were activated by stoichiometric amounts of TMSOTf (trimethylsilyl trifluoromethanesulfonate) at −30 °C and reacted at this temperature for 30 min. Then the temperature was raised to −15 °C and

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

• in 96% yield (98% de) [92][95]. A novel β-selective glycosylation of the 5'-hydroxy group was also established. Thus, 14 was reacted with the ribosyl fluoride 15 and BF3·Et2O, which afforded the glycosylated product 16 in 77% yield and with a β/α-selectivity of 24:1 [91][92]. This reaction was

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

• significant shifts of the Xyl C-2, Fuc C-3 and C-4, Rha and Rha2Me C-3 signals to a lower field of δ 77.3–81.0, as compared with their positions in the respective unsubstituted monosaccharides [19], indicated the modes of sugar glycosylation in the OPS. The C-2–C-6 chemical shifts of Glc were characteristic