Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

Synthesis of cyclic β-1,6-oligosaccharides from glucosamine monomers by electrochemical polyglycosylation

• Md Azadur Rahman,
• Hirofumi Endo,
• Takashi Yamamoto,
• Shoma Okushiba,
• Norihiko Sasaki and
• Toshiki Nokami

Beilstein J. Org. Chem. 2024, 20, 1421–1427, doi:10.3762/bjoc.20.124

• protecting group afforded the cyclic disaccharide exclusively. Cyclic oligosaccharides up to the trisaccharide were obtained using the monomer with a 2-azido-2-deoxy group. Keywords: cyclic oligosaccharide; electrochemical glycosylation; glucosamine; polyglycosylation; Introduction Electrochemical

• . However, the yield of 1,6-anhydrosugar 7b (R3 = Ac, R4 = Bn) was lower than that of 7a (Table 1, entry 2). Because no linear oligosaccharides were obtained, we reduced the amount of total charge from 1.05 to 0.525 F/mol (Table 1, entry 3). Linear disaccharide 9b (R3 = Ac, R4 = Bn) and trisaccharide 10b

• polyglycosylation using the thioglycoside monomer 17 with an N3 group are summarized in Table 2. Cyclic trisaccharide 19a was obtained together with cyclic disaccharide 18a, along with trace amount of linear and cyclic tetrasaccharides by introduction of an N3 group (Table 2, entry 1). Cyclic disaccharide 18b and

Synthesis of protected precursors of chitin oligosaccharides by electrochemical polyglycosylation of thioglycosides

• Md Azadur Rahman,
• Kana Kuroda,
• Hirofumi Endo,
• Norihiko Sasaki,
• Tomoaki Hamada,
• Hiraku Sakai and
• Toshiki Nokami

Beilstein J. Org. Chem. 2022, 18, 1133–1139, doi:10.3762/bjoc.18.117

• of oligosaccharides and/or trehalose pseudo-oligosaccharides, which were major byproducts at the elevated temperature, became stronger in the corresponding peaks of longer oligosaccharides, such as hexasaccharide 6a and heptasaccharide 7a. Proposed structures of byproducts of trisaccharide 3a

• electrochemical activation occurs at the surface of the anode and the substrates must move to the surface of the electrode. To confirm the reactivity of oligosaccharides, we measured oxidation potentials of monosaccharide 1a, disaccharide 2a, and trisaccharide 3a using a rotating disk electrode (RDE) made of

• potential of monosaccharide 1a, disaccharide 2a, and trisaccharide 3a. Influence of cycle number on the yield of longer oligosaccharides 5a (n = 5)–8a (n = 8). Conditions of anodic oxidation: constant current (8.0 mA, 0.52 F/mol), temperature −60 °C for anodic oxidation and −30 °C for glycosylation

Total synthesis of the O-antigen repeating unit of Providencia stuartii O49 serotype through linear and one-pot assemblies

• Tanmoy Halder and
• Somnath Yadav

Beilstein J. Org. Chem. 2021, 17, 2915–2921, doi:10.3762/bjoc.17.199

• , we herein report the total synthesis of a trisaccharide repeating unit of the O-antigen polysaccharide of the P. stuartii O49 serotype containing the →6)-β-ᴅ-Galp-(1→3)-β-ᴅ-GalpNAc(1→4)-α-ᴅ-Galp(1→ linkage. The synthesis of the trisaccharide repeating unit was carried out first by a linear strategy

• involving the [1 + (1 + 1 = 2)] assembly, followed by a one-pot synthesis involving [1 + 1 + 1] strategy from the corresponding monosaccharides. The one-pot method provided a higher yield of the protected trisaccharide intermediate (73%) compared to the two step synthesis (66%). The protected trisaccharide

• was then deprotected and N-acetylated to finally afford the desired trisaccharide repeating unit as its α-p-methoxyphenyl glycoside. Keywords: capsular polysaccharide; carbohydrate vaccines; O-antigen; oligosaccharide synthesis; one-pot synthesis; Introduction O-antigens or O-specific

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

A consensus-based and readable extension of Linear Code for Reaction Rules (LiCoRR)

• Benjamin P. Kellman,
• Yujie Zhang,
• Emma Logomasini,
• Eric Meinhardt,
• Karla P. Godinez-Macias,
• Austin W. T. Chiang,
• James T. Sorrentino,
• Chenguang Liang,
• Bokan Bao,
• Yusen Zhou,
• Sachiko Akase,
• Isami Sogabe,
• Thukaa Kouka,
• Elizabeth A. Winzeler,
• Iain B. H. Wilson,
• Matthew P. Campbell,
• Sriram Neelamegham,
• Frederick J. Krambeck,
• Kiyoko F. Aoki-Kinoshita and
• Nathan E. Lewis

Beilstein J. Org. Chem. 2020, 16, 2645–2662, doi:10.3762/bjoc.16.215

• rule can be extended to glycopeptides providing a means of representing glycans directly embedded in a glycopeptide. “PEP(Gal[3S]b3(GNb6)AN)TIDE” would describe a trisaccharide O-glycan bound to the threonine of an eponymously named glycoprotein. Overall, the consensus in these representations centers

Synthesis of the tetrasaccharide repeating unit of the O-specific polysaccharide of Azospirillum doebereinerae type strain GSF71^T using linear and one-pot iterative glycosylations

• Arin Gucchait,
• Pradip Shit and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2020, 16, 1700–1705, doi:10.3762/bjoc.16.141

• ]. Repeating the reaction with disaccharide acceptor 5 using the same conditions, the stereoselective glycosylation with compound 3 furnished trisaccharide acceptor 6 in 70% yield. The desired stereochemistry of the newly formed glycosidic bond was confirmed by NMR spectroscopic analysis [appearance of signals

• temperature of the reaction and coupling the in situ-generated trisaccharide derivative 6 with compound 4 to furnish the desired tetrasaccharide derivative 7 in 30% overall yield. The structure of compound 7 obtained by the three iterative glycosylation reactions in one pot fully matched with the product

Synthesis of Streptococcus pneumoniae serotype 9V oligosaccharide antigens

• Sharavathi G. Parameswarappa,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2020, 16, 1693–1699, doi:10.3762/bjoc.16.140

• -mannosidic linkage, have to be installed stereoselectively while taking provision to install the C-6 O-acetate in ManpNAc. The synthetic approach (Scheme 1) relies on a late stage [2 + 3] α-glycosylation between disaccharide 6 and trisaccharide 7 to obtain the fully protected pentasaccharide RU. The di- and

• trisaccharide will be prepared from five differentially protected building blocks (8–12) that will ensure the desired stereochemical outcome during the glycosylations. The synthesis of trisaccharide 25 commenced with the union of glucose thioglycoside 12 with C5-linker alcohol 13 to yield the corresponding

• the β-disaccharide 16 (Scheme 2). A ring-opening reaction followed by subsequent glycosylation of 19 with orthogonally protected thioglucoside 10 gave trisaccharide 21 in moderate yield. To improve the yield, the nucleophilicity of the disaccharide acceptor 19 (Scheme 2) was altered by replacing the

Convenient synthesis of the pentasaccharide repeating unit corresponding to the cell wall O-antigen of Escherichia albertii O4

• Tapasi Manna,
• Arin Gucchait and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2020, 16, 106–110, doi:10.3762/bjoc.16.12

• as thiophilic activator. Gratifyingly, the trisaccharide derivative 12 was obtained in 74% yield with a newly formed 1,2-cis glycosyl linkage in it. The structural confirmation of compound 12 was established by its NMR spectral analysis [signals at δ 5.67 (d, J = 3.0 Hz, H-1A), 5.60 (d, J = 3.5 Hz, H

• presence of tetrabutylammonium bromide (TBAB) followed by oxidative removal [33] of the PMB group using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) to give trisaccharide acceptor 13 in 72% yield. Trisaccharide acceptor 13 was then allowed to couple with ʟ-rhamnosyl trichloroacetimidate donor 5 in the

Chemical synthesis of the pentasaccharide repeating unit of the O-specific polysaccharide from Escherichia coli O132 in the form of its 2-aminoethyl glycoside

• Debasish Pal and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2019, 15, 2563–2568, doi:10.3762/bjoc.15.249

• the aforementioned target. Therefore, the first disconnection gave the trisaccharide acceptor 11 and the disaccharide donor 16. Further disconnection on the trisaccharide 11 gave disaccharide 5 and the monosaccharide 9. Disaccharide 5 is accessible from monosaccharide acceptor 2 and donor 3. Similarly

• using NIS and TMSOTf afforded the trisaccharide 10 in 78% yield. The newly formed 1,2-cis glycosidic linkage was confirmed by the peaks at 4.27 ppm (d, J1′′,2′′ = 1.5 Hz, 1H, H-1′′) in the 1H NMR and at 93.8 ppm (C-1′′) in the 13C NMR spectra. The presence of the participating O-benzoyl group at the 6-O

• -position of the donor led exclusively to the 1,2-cis glycoside [19]. Finally, the oxidative removal of the naphthyl group using DDQ [20] afforded the trisaccharide acceptor 11 in 83% yield (Scheme 2). The known galactofuranosyl derivative 12 [21] was prepared by following a literature procedure. It was

Convergent synthesis of the pentasaccharide repeating unit of the biofilms produced by Klebsiella pneumoniae

• Arin Gucchait,
• Angana Ghosh and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2019, 15, 431–436, doi:10.3762/bjoc.15.37

•  1). Initially it was planned to couple the disaccharide acceptor 13 with the trisaccharide thioglycoside donor 19 using a [3 + 2] convergent glycosylation strategy to achieve the pentasaccharide derivative 20. However, the desired product was obtained in poor yield, which did not allow upscaling of

• the synthesis. Consequently, an alternative [2 + 3] block glycosylation strategy was adopted using the disaccharide trichloroacetimidate derivative 18 as donor and trisaccharide derivative 23 as glycosyl acceptor, which resulted in the formation of target pentasaccharide derivative 20 in satisfactory

• trisaccharide thioglycoside 19 can now act as a glycosyl donor fulfilling the orthogonal glycosylation principle [36]. Stereoselective glycosylation of disaccharide acceptor 13 with the trisaccharide donor 19 in the presence of a combination of NIS and TMSOTf [22][23] resulted in the formation of

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

• -side of the ring. Having obtained the central disaccharide 3a in requisite yield and excellent stereochemical purity we now proceeded towards the synthesis of the trisaccharide fragment 21 (Scheme 4). Compound 3a was treated with DDQ in dichloromethane to remove the 3-O-Nap protection group generating

• acceptor 4 in 93% yield. Glycosylation between donor 2 and acceptor 4 was achieved uneventfully in the presence of TMSOTf in dichloromethane/Et2O (4:1) to give the trisaccharide 21 in 70% yield. Successful glycosylation was also carried out between trisaccharide 21 and ribitol acceptor 7 in the presence of

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

• Shoda [32] and co-workers reported that a disaccharide oxazoline (Scheme 1) was an effective donor substrate for two ENGase enzymes (Endo A and Endo M), both of which were capable of using it to glycosylate two GlcNAc acceptors, to produce trisaccharide products. Subsequently the ENGases in combination

• synthetic methodology, and so in principle the locust bean gum approach should allow rapid access to a wide variety of more extended N-glycan structures. In their original publication Nishimura and co-workers first glycosylated the free OH at position 3 with 2,4-branched trisaccharide trichloroacetimidate

• donor 2, removed the 4,6-benzylidene, and then regioselectively glycosylated the free primary OH at position 6 with 2,6-branched trisaccharide trichloroacetimidate donor 3. Following conversion of the Troc groups into acetamides and reduction and acetylation of the azide, all of the acetates were

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

• separation of the anomeric α/β mixture furnished the anomerically pure trisaccharide 15. Next, three acyl residues were introduced at positions 2’, 3’ and 3 by successive deprotection–acylation sequence. The N-Fmoc protecting group was removed using DBU and the resulting free amino group was acylated with (R

• regioselective reductive opening of 4′,6′-O-benzylidene acetal in 28 with Me2NH·BH3 and BF3·OEt2 in chloroform as solvent. The glycosylation of 34 with Kdo donor 35 was performed in CPME ether in the presence of TBSOTf as promotor to result in the stereoselective formation of trisaccharide 36. Alternative

• lactol was phosphorylated via phosphoramidite procedure to furnish fully protected trisaccharide phosphodiester 40, which was deprotected by hydrogenolysis on Pd(OH)2/C in THF/H2O/AcOH to give H. pylori lipid A 41. The availability of pure homogeneous synthetic compounds allowed for extensive

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

• , producing trisaccharide selenoglycoside 11 in 90% yield (Scheme 4). Following the same reaction protocol trisaccharide 11 and glycosylated acceptor 9 lead to tetrasaccharide 12, which was further extended to heptasaccharide 13. This method has also been applied to generate a library of phytoalexin elicitor

• was then subjected to another round of Tf2O-mediated glycosylation leading to trisaccharide 20 in one pot (Scheme 5b). As compounds 16 and 20 have relatively simple structures, the scope of this 2-pyridyl glycosylation method will need to be established in the total synthesis of more complex

• acceptor 41 to the reaction mixture furnished trisaccharide 42. This approach was applied to the synthesis of hyaluronic acid (HA) oligomers [39]. The sequential reaction of building blocks 43, 44 and 46 led to HA trisaccharide 47 (Scheme 10). The modest overall yield of 26% for the two glycosylation

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

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

• conformations and energies chose the latter linker [55]. To apply the remote glycosidation methodology to the synthesis of the 4,6-branched trisaccharide, phthaloylated thioglycoside 17 was coupled with the 6-hydroxy group of the acceptor precursor 16 in the presence of DCC and DMAP (Scheme 5). The tethering

• remote glycosidation of 18 was conducted in the presence of Cp2HfC12 and AgOTf in CH2C12 under reflux. The cyclized product 19 was obtained in 37% yield, the tether was removed with NaOMe, and the resulting free hydroxy groups were acetylated to afford the branched trisaccharide 20. The chemical

• liberating the hydroxy group at C-4’ gave the tethered donor–acceptor combination 36. After the NIS/TfOH-promoted glycosylation the desired trisaccharide 37 was obtained in 75% yield as a pure α-linked diastereomer. The per-acetylated maltotriose target was obtained after palladium-catalyzed hydrogenation

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

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

• -SIGN targeting through GAuNPs has also been exploited differently in a study on GAuNPs functionalized with α-fucosylamide, an efficacious synthetic DC-SIGN ligand, analogue of the natural fucose-containing Lewisx trisaccharide [98]. This paper shows that GAuNPs bearing 50% of fucosylamide are able to

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

• trisaccharide 6 as an intermediate after the 1st cycle. The same process was repeated automatically in the 2nd cycle and target tetrasaccharide 7 was obtained in 41% yield after purification by preparative gel permeation chromatography (GPC). Deprotection and introduction of the TMG part to tetrasaccharide 7

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

• vaccines is the assembly of the trisaccharide β-D-GalpNAc-(1→4)-[α-D-Glcp-(1→3)]-β-D-ManpNAcA, in which the branching points are equipped with orthogonal protecting groups. A linear approach relying on the sequential assembly of monosaccharide building blocks proved superior to a convergent [3 + 3

• 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

• Information File 1). Cleavage of the silyl ether by TBAF treatment of 15 afforded the β-mannosazide building block 18. Convergent [3 + 3] synthesis. Synthesis of the reducing-end trisaccharide 3 (Scheme 1) commenced with the assembly of the α-1→2 linked diglucoside 19 by union of the monosaccharide building

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

• Lewis X trisaccharide: The reaction of 7 with disaccharide 8 promoted by dimethyl disulfide and triflic anhydride gave trisaccharide 9 with high α-selectivity (Scheme 3) [12]. These conditions, using this promoter system, worked fine in a number of similar cases. The less-stable trimethylsilyl group has

• together with all reagents from the start (Scheme 5). The activation of the individual donors was controlled by changing the temperature and the trisaccharide donor 33 could thereby be prepared in excellent yields [21]. The reactivity of silylated donors have also been investigated by Hung, Wong and

• than the corresponding benzylated thioglycosides in competition reactions and used the reactivity differences in a one-pot glycosylation reaction between 37, a disarmed donor/acceptor 38 and an acceptor 39, which gave the trisaccharide 40 in a remarkable yield of 88% (Scheme 7). This reaction works so

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

• of trisaccharide 66. Iterative synthesis of trisaccharide 66. Proposed mechanisms for TMSBr-mediated synthesis of 2-deoxyglycosides in the presence of TPPO. TMSBr-mediated thio-addition of glycals. Additives in TMSBr-mediated 2-deoxyglycosylation of glucal 1. TMSBr-mediated 2-deoxyglycosylation of

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

• 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

• irradiation with UV light in a flow reactor [28] and analyzed by normal-phase HPLC (Figure 3). Trisaccharide 6 lacking one C2-benzoate ester protecting group was identified as the main product. The unexpected side reaction was attributed to the basicity of the Fmoc deprotection solution. In addition, two

• -protected 3. The use of the buffered hydrazine solution for the cleavage of Lev TPGs was expected to prevent any undesired benzoyl ester cleavage. The trisaccharide synthesis was repeated using the same glycosylation conditions as in the previous synthesis (Scheme 2). After each glycosylation step, the pH

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• the cyclohexene systems. RRM of cyclopentene system 74. RRM approach to compound 79. RRM approach to spirocycles. RRM approach to bicyclic dihydropyrans. RCM–ROM–RCM cascade using non strained alkenyl heterocycles. First ROM–RCM–ROM–RCM cascade for the synthesis of trisaccharide 97. RRM of cyclohexene

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• available N-hydroxysuccinimide (NHS)-carboxy-dT phosphoramidite 5 (Scheme 3). This method allows the sequential introduction of any amine-functionalized glycan during DNA synthesis and was shown to be compatible with more complex glycans such as Lewis X trisaccharide. The capping step in DNA synthesis