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

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• ]. The recombinant CgiA enzyme was produced in B. subtilis and its biochemical characterization revealed it exhibited maximal activity at 50 °C. It can break ι-carrageenan into tetrasaccharide at high proportion. A conserved Glu351, rather than an Asp, was identified as the catalytic residue by site

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• kinetics allowed us to derive an IC50 of 1.4 µM (Figure S2a,b; Supporting Information File 2). No inhibition was observed with chondroitin 6-sulfate tetrasaccharide (CSC), and only very weak inhibition for BGHT2 but no IC50 could be determined as we could not increase the concentration to reach the plateau

• (BioRad). 0.6 mg/mL protein in PBS was mixed with SYPRO Orange (Sigma-Aldrich, Merck, #S5692) and glycan ligand (10 mM GalNAc; Carbosynth, #MA04390; 10 mM GlcNAc, Carbosynth, #MA00834; 10 mM blood group H type-2 tetrasaccharide; Elicityl, GLY032-2) in a total reaction volume of 25 µL. The temperature was

Sulfur-containing spiroketals from Breynia disticha and evaluations of their anti-inflammatory effect

• Ken-ichi Nakashima,
• Naohito Abe,
• Masayoshi Oyama,
• Hiroko Murata and
• Makoto Inoue

Beilstein J. Org. Chem. 2023, 19, 1604–1614, doi:10.3762/bjoc.19.117

• ) in 1D and 2D ROE spectroscopy (ROESY) suggested that the relative configuration of the aglycone in 1 is identical to that in breynin B (6). The remaining NMR resonances (Table 2) were attributed to a tetrasaccharide based on the observation of four anomeric methine signals at δC 103.2 (C-1′), 104.5

• spiroketals (1 and 2) with a tetrasaccharide moiety. For terpenoid glycosides, the 1H NMR spectrum becomes more complex as the number of sugar residues and their lengths increase, which complicates 2D NMR analysis. In such cases, commonly used TOCSY measurements can be supplemented by H2BC and HSQC-TOCSY

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

• V vs SCE) gave oligosaccharides up to hexasaccharide 6a, although the yield of pentasaccharide 5a (3%) and hexasaccharide 6a (1%) was very low. For thioglycoside 1b (Ar = 4-ClC6H4, Eox = 1.68 V vs SCE), the highest conversion (79%) and the highest yield of tetrasaccharide 4b (14%) were observed

• . Contrary, thioglycoside 1c (Ar = 4-MeC6H4, Eox = 1.47 V vs SCE), which had the lowest oxidation potential, showed the lowest conversion (51%) and the lowest yield of tetrasaccharide 4c (2%) [8]. This being the case, lower conversion of the building block 1c and lower yield of oligosaccharides 2c–4c

• with the glycosylation temperature (T2) because glycosylation must occur during the anodic oxidation at elevated temperature (Figure 4). Indeed, formation of oligosaccharides longer than tetrasaccharide 4a was increased at elevated temperature. The highest total yield of oligosaccharides 2a–7a was

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

• ) and p-methoxybenzyl (PMB) PGs could be selectively cleaved to allow for chain elongation and for introduction of the Gal unit at the C-2 of the xylopyranose, respectively. An alternative approach utilized natural sourced XLLG tetrasaccharide, which was obtained from tamarind seed XG via enzymatic

• (1–3)-Xyl hexamer, an analogue of xylans found in algae cell-walls [206]. TMSOTf promoted the glycosylation of the Bz-protected disaccharide acceptor with the Bz-protected tetrasaccharide trichloroacetimidate donor. Although not yet reported, the authors suggested that this method can be extended to

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

• Arin Gucchait Pradip Shit Anup Kumar Misra Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII M, Kolkata 700054, India 10.3762/bjoc.16.141 Abstract A straightforward synthetic strategy was developed for the synthesis of the tetrasaccharide repeating unit corresponding to

• glycosyl activator. Keywords: Azospirillum doebereinerae; glycosylation; HClO4-SiO2; O-polysaccharide; tetrasaccharide; Introduction The development of plant-growth-promoting agents has become an attractive area of research in the agricultural sciences to reduce the need for chemical fertilizers, which

• ]. Recently, Sigida and co-workers reported the structure of the tetrasaccharide repeating unit of the O-specific polysaccharide of Azospirillum doebereinerae type strain GSF71T, which is composed of three α-ʟ-rhamnose units and one β-ᴅ-glucosamine moiety [21]. It also contains two O-acetyl groups which might

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

• disaccharide acceptor 9 and the disaccharide thioglycoside donor 10, a stereoselective glycosylation between them was attempted in the presence of a combination [26][27] of NIS and HClO4/SiO2 as thiophilic activator. Unfortunately, the required tetrasaccharide derivative 11 was obtained in a poor yield (22

• presence of HClO4/SiO2 as a solid acid activator [31] to provide tetrasaccharide derivative 11 in 76% yield, which was de-O-acetylated to furnish tetrasaccharide acceptor 14 in 94% yield. The formation of compound 11 with appropriate configuration at the glycosidic linkages was supported by its NMR

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• ; galectin-1; hydroboration; inhibition; selective; triazole; Introduction Galectins are defined by a typically about 130 amino acid carbohydrate recognition domain (CRD) that binds to carbohydrates with at least one β-galactose subunit within a binding pocket large enough to accommodate a tetrasaccharide

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

• -assisted synthesis of chondroitin sulfate (CS) oligosaccharides. Following this approach, a CS tetrasaccharide was prepared. However, in contrast to our previous results, a significant loss of β-selectivity was observed in [2 + 2] glycosylations involving N-trifluoroacetyl-protected D-galactosamine donors

• buffer afforded compound 2. With the required disaccharide building blocks in hand, the synthesis of tetrasaccharide 14β was attempted using catalytic TMSOTf in CH2Cl2 at 0 ºC (Scheme 4). After F-SPE, two spots were detected in the TLC analysis of the fluorous containing fraction, in addition to

• temperature (−20 ºC), typical conditions for favoring the formation of the β-bond, increased the β-selectivity (1:4 α/β ratio) but also decreased the overall yield (50%). Similarly, a loss of β-selectivity was observed at the hexasaccharide stage (Scheme 7). Tetrasaccharide acceptor 20 was prepared from 19β

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

• conjugate in proper amounts for future vaccine development can only be met via chemical synthesis. Therefore, a number of syntheses targeting the SPn 6A tetrasaccharide has been reported in literature. Initial reports of a linear synthesis were made by Vliegenthart et al. in the nineties [17][18][19][20][21

• ]. After this, the Demchenko group improved these early reports with a convergent approach using glycosyl thioimidates as complementary glycosyl donors with respect to thioglycosides [22][23][24][25]. Herein, we wish to report synthetic routes to the SPn 6A tetrasaccharide via stepwise as well as one-pot

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

• -tetrasaccharide 1 was made in which the recognition units, the terminal galactose and Neu5Ac, were attached onto the DCCHD scaffold. Inhibition assays of the oligosaccharide mimetic with CT and LT showed similar potency as that of natural ligands [32]. But, the alpha-sialylation was the bottleneck step in the

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

• the GlcNAc acceptor has an azide or sulfonamide at position 2, rather than acetamide or N-phthalamide. Scheme 5 shows an example of the synthesis of a modified core N-glycan tetrasaccharide oxazoline from the several reported by Wang [77] using this approach. In this case following formation of the

• synthetic tetrasaccharide, to which other species were then conjugated by click reactions. In more recent examples conversion of the completely deprotected glycan to the oxazoline by treatment with DMC has become the normal (and most effective) strategy. For example the same key Manβ(1–4)GlcNAc disaccharide

• ][80], including those bearing mannose-6-phosphate residues [45][46]. For example as shown in Scheme 7 sequential glycosylation of the key Manβ(1–4)GlcNAc disaccharide at positions 3 and 6, using the same selectively protected manno thioglycoside donor gave a tetrasaccharide. Removal of the silyl

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

• successful mannose recognition domain? In general, lectins are characterized by high ligand specificity, whereas the affinity for their carbohydrate ligands is comparatively low. A prominent example is sialyl Lewisx (sLex), a tetrasaccharide typically O-linked to cell surfaces and known to play a vital role

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

• without the need for any protective group manipulation or aglycon adjustment. Using this method, the 1,4-α-linked tetrasaccharide 37 was prepared in good overall yield. Inspired by Gin’s work, van der Marvel and co-workers developed a sequential glycosylation strategy by combining hemiacetal and

• applicability of this method, a linear tetrasaccharide was synthesized bearing a ketone tag at the reducing end using building blocks 83, 150 and 151 following the preactivation-based one-pot protocol (Scheme 22). After completion of the synthesis, a fluorinated hydrazide 152 was added to the reaction mixture

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

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

• was glycosylated in the presence of NIS/TfOH to afford tetrasaccharide 32 in 78% as a pure β-diastereomer [70]. Schmidt demonstrated the usefulness of xylylene tethers in application to the iterative synthesis of maltotriose [70]. In this application, the xylylene tether was used to link two glucose

• stereoselectivity. Advantages of this methodology have been tested in application to the synthesis of a tetrasaccharide repeating unit of lipopolysaccharide derived from E. coli O75 [111]. Demchenko and co-workers introduced the use of the picolinyl group at the neighboring C-2 position of glycosyl donors as an

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

• designing an ELISA approach to detect anti-carbohydrate antibodies. The innovative procedure exploited the use of very small AuNPs (2 nm) coated with tetrasaccharide epitopes of HIV gp120 or tetrasaccharide epitopes of Streptococcus pneumoniae Pn14PS. The GAuNPs so obtained were directly coated on

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

• -chitotriomycin using an automated electrochemical synthesizer for the assembly of carbohydrate building blocks is demonstrated. We have successfully prepared a precursor of TMG-chitotriomycin, which is a structurally-pure tetrasaccharide with typical protecting groups, through the methodology of automated

• synthesizer for the automated electrochemical assembly of carbohydrate building blocks [25]. During the course of our study, we have achieved the synthesis of a potential precursor of TMG-chitotriomycin (1); however, we obtained the tetrasaccharide as a mixture of α- and β-isomers in the terminal glycosidic

• 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

• activator proceeded to produce trisaccharide 44 in 65% yield. Removal of the C2 naphthyl ether using DDQ provided acceptor 45, which in turn was reacted with glucosyl thioglycoside 7 in the presence of NIS and TfOH to produce α-linked tetrasaccharide 46 in 62% yield (Scheme 8). At this stage, the 2

• -azidomannose moiety of 46 was converted to the corresponding mannosaminuronic acid by cleaving the C6 benzoate ester using sodium methoxide in methanol and selective oxidation of the primary alcohol of 47 using BAIB/TEMPO. Tetrasaccharide acceptor 48 was obtained by esterification of the carboxylic acid under

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

• tetrasaccharide addition sequence, resulting from benzoyl ester cleavage and a double glycosylation in the last step (see Supporting Information File 1). This result was not expected as the buffered hydrazine deprotection protocol had never favored the formation of side products in our hands. However, this

Synthesis of a hexasaccharide partial sequence of hyaluronan for click chemistry and more

• Marina Bantzi,
• Stephan Rigol and
• Athanassios Giannis

Beilstein J. Org. Chem. 2015, 11, 604–607, doi:10.3762/bjoc.11.67

• disaccharides were coupled through initial activation of 4 with NIS and TfOH to furnish the corresponding protected tetrasaccharide. Furthermore, treatment of the glycosylation product with Olah's reagent and an additional amount of pyridine generated the tetrasaccharide glycosyl acceptor 6 by removal of the

• with tetrasaccharide 6. The underlying protecting group pattern with a selectively cleavable silyl group at the non-reducing end of the saccharide sequence permits the further elongation by additional iterative cycles based on the presented methodology. Then, the N-Troc groups were cleaved under mild

Cyclodextrin–polysaccharide-based, in situ-gelled system for ocular antifungal delivery

• Anxo Fernández-Ferreiro,
• Noelia Fernández Bargiela,
• María Santiago Varela,
• Maria Gil Martínez,
• Maria Pardo,
• Antonio Piñeiro Ces,
• José Blanco Méndez,
• Miguel González Barcia,
• Maria Jesus Lamas and
• Francisco.J. Otero-Espinar

Beilstein J. Org. Chem. 2014, 10, 2903–2911, doi:10.3762/bjoc.10.308

• electrical field, which result in the modification of its structure and properties [11]. Gellan gum (GG) and carrageenans are polysaccharides that can be used to enhance ion-sensitive hydrogels. Gellan gum is a linear anionic heteropolysaccharide with high molecular mass formed by a tetrasaccharide repeating

Galactan synthesis in a single step via oligomerization of monosaccharides

• Marius Dräger and
• Amit Basu

Beilstein J. Org. Chem. 2014, 10, 2658–2663, doi:10.3762/bjoc.10.279

• the reaction using donor 2, which lacks a silyl protecting group on the primary hydroxy group, proved to be remarkably clean, providing products ranging from the monosaccharide to the tetrasaccharide in isolable yield (Table 1, entry 4). In all of the reactions carried out thus far, we noticed that

Efficient routes toward the synthesis of the D-rhamno-trisaccharide related to the A-band polysaccharide of Pseudomonas aeruginosa

• Aritra Chaudhury,
• Sajal K. Maity and
• Rina Ghosh

Beilstein J. Org. Chem. 2014, 10, 1488–1494, doi:10.3762/bjoc.10.153

• tetrasaccharide, α-D-Rhap-(1→2)-α-D-Rhap-(1→3)-α-D-Rhap-(1→3)-α-D-Rhap [17] and a trisaccharide, α-D-Rhap-(1→3)-α-D-Rhap-(1→2)-α-D-Rhap [18] related to the A-band polysaccharide of P. aeruginosa were made with a view to develop glycoconjugate vaccines, but none have ultimately materialized into valid vaccine

Convergent synthesis of a tetrasaccharide repeating unit of the O-specific polysaccharide from the cell wall lipopolysaccharide of Azospirillum brasilense strain Sp7

• Pintu Kumar Mandal,
• Debashis Dhara and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2014, 10, 293–299, doi:10.3762/bjoc.10.26

• -700054, India 10.3762/bjoc.10.26 Abstract A straightforward convergent synthesis has been carried out for the tetrasaccharide repeating unit of the O-specific cell wall lipopolysaccharide of the strain Sp7 of Azospirillum brasilense. The target tetrasaccharide has been synthesized from suitably

• protected monosaccharide intermediates in 42% overall yield in seven steps by using a [2 + 2] block glycosylation approach. Keywords: Azospirillum brasilense; glycosylation; lipopolysaccharide; plant growth-promoting bacteria (PGPB); tetrasaccharide; Introduction The intensive use of chemicals for the

• well-known role in interactions between plants and bacteria [16][17][18][19][20][21]. Recently, Sigida et al. reported the structure of the repeating unit of the LPS present in the cell wall of Azospirillum brasilense strain Sp7: a tetrasaccharide consisting of D-galactose, D-glucosamine, L-rhamnose