Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

• Laura Morelli,
• Damiano Cancogni,
• Marta Tontini,
• Alberto Nilo,
• Sara Filippini,
• Paolo Costantino,
• Maria Rosaria Romano,
• Francesco Berti,
• Roberto Adamo and
• Luigi Lay

Beilstein J. Org. Chem. 2014, 10, 2367–2376, doi:10.3762/bjoc.10.247

• ), sera elicited by the monomer 1 exhibited low anti-trimer antibodies, whereas sera induced by the conjugated dimer 2 and the trimer 3 possessed comparable levels of antibodies against the trisaccharide structure. The IgG levels raised by the trimer-CRM197 conjugate 16 were in turn significantly lower (p

• 0.0005) than those elicited by the MenXDP15-CRM197 conjugate 17, where the trisaccharide is repeated multiple times. We hypothesize that the improved binding of antibodies induced by 14 and, primarily, by 15 to the coated trisaccharide conjugate rather than to 1- and 2-HSA conjugates, respectively, might

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

• Aritra Chaudhury Sajal K. Maity Rina Ghosh Department of Chemistry, Jadavpur University, Kolkata 700 032, India 10.3762/bjoc.10.153 Abstract The present work describes efficient avenues for the synthesis of the trisaccharide repeating unit [α-D-Rhap-(1→3)-α-D-Rhap-(1→3)-α-D-Rhap] associated with

• allowed efficient access to the trisaccharide target via stepwise glycosylation as well as a one-pot glycosylation protocol. In a different approach, a 4,6-O-benzylidene D-manno-trisaccharide derivative was synthesized, which upon global 6-O-deoxygenation followed by deprotection generated the target D

• -rhamno-trisaccharide. The application of the reported regioselective radical-mediated deoxygenation on 4,6-O-benzylidene D-manno thioglycoside (hitherto unexplored) has potential for ramification in the field of synthesis of oligosaccharides based on 6-deoxy hexoses. Keywords: A-band polysaccharide; D

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• antibiotic is aclacinomycin A, which has been used clinically under the name aclarubicin. It is an anthracycline [10] bearing a trisaccharide side chain consisting of L-rhodosamin, 2,6-didesoxy-L-lyxose, and L-cinerulose attached to the aglycon aclavinon [11][12]. It was found to be a potent antineoplastic

Gold-catalyzed glycosidation for the synthesis of trisaccharides by applying the armed–disarmed strategy

• Abhijeet K. Kayastha and
• Srinivas Hotha

Beilstein J. Org. Chem. 2013, 9, 2147–2155, doi:10.3762/bjoc.9.252

• trisaccharide. Instead, disaccharide 3 (53%) and 1,6-anhydro sugar 5 (20%) were isolated as major products [37]. Interestingly, propargyl mannoside 1 (12%) along with benzyl glycoside 6 and lactol 7 were noticed in 5% and 4% yield, respectively (Scheme 1). The Brønsted acid (HBr) released from AuBr3 in the

• (19) under aforementioned modified gold-catalysis conditions (Scheme 4). The strong armed–disarmed effects that were observed for the Ech-donors at 25 °C encouraged us to continue the use of the armed–disarmed strategy for the trisaccharide synthesis. Accordingly, the armed mannosyldonor 15j was

• two steps. The glycosylation between disaccharide 24 and disarmed aglycon 16 was performed under aforementioned conditions for a gold-catalyzed transglycosidation. Purification by conventional silica gel column chromatography enabled us to characterize the anticipated trisaccharide 25 (21%) along with

Synthesis of mucin-type O-glycan probes as aminopropyl glycosides

• David Benito-Alifonso,
• Rachel A. Jones,
• Anh-Tuan Tran,
• Hannah Woodward,
• Nichola Smith and
• M. Carmen Galan

Beilstein J. Org. Chem. 2013, 9, 1867–1872, doi:10.3762/bjoc.9.218

• -deoxy-D-galactose to serine or threonine. This saccharide forms the inner part of the characteristic core oligosaccharides from where glycans are extended through common core (di- and trisaccharide) structures, cores 1–8 [6][7][8]. The mucin-type oligosaccharides identified to date have remarkable

• %) to yield final targets 2 and 3 in 60% and 70% yield, respectively (Scheme 1). Access to branched core 2 trisaccharide 4 was accomplished by 4,6-O-benzylidene acetal cleavage from disaccharide 15 using a modified procedure from Chang et al. [21] whereby reaction with p-TsOH in MeOH under sonication

• yielded 4,6-diol 16 in less than 30 minutes at room temperature. Disaccharide 16 was then regio- and stereoselectively glycosylated with N-Troc protected glucosamine donor 12 taking advantage of the higher reactivity of the primary OH at C-6 with respect to the C-4 OH group and trisaccharide 17 was

Straightforward synthesis of a tetrasaccharide repeating unit corresponding to the O-antigen of Escherichia coli O16

• Manas Jana and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 1757–1762, doi:10.3762/bjoc.9.203

• using sodium methoxide furnished the trisaccharide acceptor 8 in 94% yield. The stereoselective glycosylation of compound 8 with D-galactofuranosyl thioglycoside 5 by using a combination of NIS/TfOH furnished the tetrasaccharide derivative 9 in 72% yield. The formation of compound 9 was supported by its

Short synthesis of the common trisaccharide core of kankanose and kankanoside isolated from Cistanche tubulosa

• Goutam Guchhait and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 705–709, doi:10.3762/bjoc.9.80

• Goutam Guchhait Anup Kumar Misra Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII M, Kolkata 700054, India 10.3762/bjoc.9.80 Abstract A short synthetic approach was developed for the synthesis of a common trisaccharide core found in kankanose, kankanoside F, H1, H2, and I

• isolated from the medicinally active plant Cistanche tubulosa. All glycosylations were carried out under nonmetallic reaction conditions. Yields were very good in all intermediate steps. Keywords: Cistanche tubulosa; glycosylation; kankanoside; synthesis; trisaccharide; Introduction Cistanche tubulosa (C

• best option to gain access to these compounds on a large scale. A few reports are available in the literature for the synthesis of phenylethyl oligosaccharides [8][9]. In this context, we developed a synthetic strategy for the synthesis of the common trisaccharide core of kankanose, kankanoside F, H1

Synthesis of a derivative of α-D-Glcp(1->2)-D-Galf suitable for further glycosylation and of α-D-Glcp(1->2)-D-Gal, a disaccharide fragment obtained from varianose

• Carla Marino,
• Carlos Lima,
• Karina Mariño and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2012, 8, 2142–2148, doi:10.3762/bjoc.8.241

• trisaccharide units of β-Galf in the backbone linked 1→5 and 1→6, synthesized in our laboratory and by other groups [19][20], are good substrates for studying the branching by the disaccharide. This may occur by sequential incorporation of Galf and then Glcp, or of the preformed disaccharide α-D-Glcp(1→2)-D-Gal

Automated synthesis of sialylated oligosaccharides

• Davide Esposito,
• Mattan Hurevich,
• Bastien Castagner,
• Cheng-Chung Wang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 1601–1609, doi:10.3762/bjoc.8.183

• was the glycosylation of compound 14 with building block 4 (Scheme 2), which proceeded efficiently in the presence of trimethylsilyl triflate (TMSOTf) as promoter at −10 °C to afford trisaccharide 15 with a yield of 80%. It is worth mentioning that glycosylation of an analogue of glucose 14 equipped

• hydrogenolysis affording good yields of the trisaccharide 16, equipped with an amino spacer for conjugation. The synthesis of GM3 trisaccharide 16 proved that compound 4 is efficient for installing the capping sialyl α-(2→3) galactose unit into synthetic oligosaccharides. Furthermore, conditions applied to the

• temperature (0 °C) and longer time (2 h) proved sufficient to drive the reaction to higher conversion and trisaccharide 19 was isolated in 33% overall yield with respect to resin loading. Hydrogenolysis under standard conditions afforded the fully deprotected trisaccharide 20 in 78% yield. These conditions

Synthesis of 4” manipulated Lewis X trisaccharide analogues

• Christopher J. Moore and
• France-Isabelle Auzanneau

Beilstein J. Org. Chem. 2012, 8, 1134–1143, doi:10.3762/bjoc.8.126

• Christopher J. Moore France-Isabelle Auzanneau Department of Chemistry, University of Guelph, 50 Stone Rd. East, Guelph, Ontario, N1G 2W1, Canada 10.3762/bjoc.8.126 Abstract Three analogues of the Lex trisaccharide antigen (β-D-Galp(1→4)[α-L-Fucp(1→3)]-D-GlcNAcp) in which the galactosyl residue

• adenocarcinomas. In addition, an association between the fucosylation of internal GlcNAc residues in polylactosamine chains, and metastasis and tumor progression in colorectal cancers has been suggested [1][2][3][4][5][6]. Unfortunately, dimLex displays the Lex trisaccharide (β-D-Galp(1→4)[α-L-Fucp(1→3)]-D

• weakly recognise Lex trisaccharide antigen [1][2][3][4][5][6]. With this in mind, we focus our research on the discovery of analogues of dimLex that can be used as safe vaccine candidates. Ideally, these analogues should display the internal epitopes that are recognized by anti-dimLex SH2-like antibodies

Triterpenoid saponins from the roots of Acanthophyllum gypsophiloides Regel

• Elena A. Khatuntseva,
• Vladimir M. Men’shov,
• Alexander S. Shashkov,
• Yury E. Tsvetkov,
• Rodion N. Stepanenko,
• Raymonda Ya. Vlasenko,
• Elvira E. Shults,
• Genrikh A. Tolstikov,
• Tatjana G. Tolstikova,
• Dimitri S. Baev,
• Vasiliy A. Kaledin,
• Nelli A. Popova,
• Valeriy P. Nikolin,
• Pavel P. Laktionov,
• Anna V. Cherepanova,
• Tatiana V. Kulakovskaya,
• Ekaterina V. Kulakovskaya and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2012, 8, 763–775, doi:10.3762/bjoc.8.87

• similar sets of two oligosaccharide chains, which are 3-O-linked to the triterpenoid part trisaccharide α-L-Arap-(1→3)-[α-D-Galp-(1→2)]-β-D-GlcpA and pentasaccharide β-D-Xylp-(1→3)-β-D-Xylp-(1→3)-α-L-Rhap-(1→2)-[β-D-Quip-(1→4)]-β-D-Fucp connected through an ester linkage to C-28. The structures of the

• bidesmosidic nature of the genin, which is glycosydated at C-3 and esterified to an oligosaccharide. The structures of both the trisaccharide and pentasaccharide fragments of compound 2 are similar to those established for compound 1. Thus the structure of 2 was elucidated as gypsogenin 28-O-β-D-xylopyranosyl

• earlier [18]. In the published structures β-D-Quip (residue e) is located at O-2 of the β-Fucp (residue d), and the trisaccharide moiety β-D-Xyl-(1→3)-β-D-Xyl-(1→3)-α-L-Rha is at O-4. The acute-toxicity study of saponins 1 and 2 was carried out on albino mice. The median lethal dose (LD50) was determined

Chemo-enzymatic modification of poly-N-acetyllactosamine (LacNAc) oligomers and N,N-diacetyllactosamine (LacDiNAc) based on galactose oxidase treatment

• Christiane E. Kupper,
• Ruben R. Rosencrantz,
• Birgit Henßen,
• Helena Pelantová,
• Stephan Thönes,
• Anna Drozdová,
• Vladimir Křen and
• Lothar Elling

Beilstein J. Org. Chem. 2012, 8, 712–725, doi:10.3762/bjoc.8.80

• File 1) and revealed the formation of trisaccharide 9a with an internal 6-aldehyde group. Moreover, further elongation of 9a by β4Gal-transferase yielded the product 10a (Scheme 2B) as analysed by ESI–MS (Table S1 and Figure S13 in Supporting Information File 1). A second oxidation round led to the

• chemical β-elimination the corresponding α,β-unsaturated aldehydes (7a–d, 8). Enzymatic modifications of oxidised poly-LacNAc oligomers. A: Elongation of LacNAc-6-aldehyde 3a by β3-N-acetylglucosaminyltransferase (β3GlcNAc-transferase) leads to internally modified trisaccharide 9a. B: The trisaccharide 9a

• reduced with Na[BH3(CN)] to the corresponding hydrazines (15a–c and 16a). B: Elongation of biotinylated LacNAc (15a) and biotinylated tetrasaccharide (15b) by β3-N-acetylglucosaminyltransferase (β3GlcNAc-transferase) leads to an internally modified trisaccharide 16a as the enzymatic elongation of the

2-Allylphenyl glycosides as complementary building blocks for oligosaccharide and glycoconjugate synthesis

• Hemali D. Premathilake and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2012, 8, 597–605, doi:10.3762/bjoc.8.66

• leading to trisaccharide 30 in 90% (Scheme 3). Since 30 is equipped with the SPh anomeric leaving group, it is available for further chain elongation directly. In a similar fashion, thioglycoside disaccharide 16 was coupled with AP acceptors 25 and 13 in the presence of MeOTf to afford trisaccharides 31

Synthesis of glycoconjugate fragments of mycobacterial phosphatidylinositol mannosides and lipomannan

• Benjamin Cao,
• Jonathan M. White and
• Spencer J. Williams

Beilstein J. Org. Chem. 2011, 7, 369–377, doi:10.3762/bjoc.7.47

• : α-Man-1,6-α-Man, α-Man-1,6-α-Man-1,6-α-Man, α-Man-1,2-α-Man-1,6-α-Man and 2,6-di-(α-Man)-α-Man. The synthesis includes the use of non-benzyl protecting groups compatible with the azido group and preparation of the branched trisaccharide structure 2,6-di-(α-Man)-α-Man through a double glycosylation

• achieved by glycosylation of 14 with the thioglycoside donor 21 [41] using NIS/TfOH in 84% yield (Scheme 4). The protected trisaccharide 25 was prepared by an approach similar to that reported for the corresponding octyl trisaccharide [22][23]. Thus glycosylation of 14 with the silylated donor 22 using NIS

• measurement of the 1JC,H coupling constants for the anomeric carbons of the newly formed products. Each coupling constant was >170 Hz, thereby showing that all new O-glycosidic linkages were α-configured (Supporting Information File 2) [42]. Global debenzoylation of disaccharide 20 and trisaccharide 25 with

A bivalent glycopeptide to target two putative carbohydrate binding sites on FimH

• Thisbe K. Lindhorst,
• Kathrin Bruegge,
• Andreas Fuchs and
• Oliver Sperling

Beilstein J. Org. Chem. 2010, 6, 801–809, doi:10.3762/bjoc.6.90

• trisaccharide substructures, mainly α-D-Man-(1→3)-[α-D-Man-(1→6)]-D-Man. By employing site directed mutagenesis, it was found that mutations in one of these cavities significantly reduces binding, indicating that this could be a second carbohydrate binding site, relevant for ligand binding [21]. Thus, it was

• mannotrioside. Hence, a monomeric mannoside and the trisaccharide α-D-Man-(1→3)-[α-D-Man-(1→6)]-D-Man were selected as carbohydrate ligands and azidoethyl aglycone moieties were chosen to allow their ligation via an oligoglycine spacer of an appropriate length. The well-known squaric acid diester linkage

• strategy [25] was applied to connect the monosaccharide and the trisaccharide part of the bivalent glycopeptide target structure 1 (Figure 2). Accordingly, retrosynthetic analysis of 1 leads to the 2-azidoethyl glycosides 2 and 5, with the azido group masking an amino function; two pentaglycine spacer

Synthesis of 6-PEtN-α-D-GalpNAc-(1–>6)-β-D-Galp-(1–>4)-β-D-GlcpNAc-(1–>3)-β-D-Galp-(1–>4)-β-D-Glcp, a Haemophilus influenzae lipopolysacharide structure, and biotin and protein conjugates thereof

• Andreas Sundgren,
• Martina Lahmann and
• Stefan Oscarson

Beilstein J. Org. Chem. 2010, 6, 704–708, doi:10.3762/bjoc.6.80

• from 7, Scheme 2). NIS/AgOTf-promoted glycosidation of this acceptor with donor 10 [19] (1.4 equiv) then efficiently gave the β-linked trisaccharide 11 (83%). At this stage the phthalimido group was removed by aminolysis and the resulting amino compound acetylated to yield 12 (93%) with the target

Chemical synthesis using enzymatically generated building units for construction of the human milk pentasaccharides sialyllacto-N-tetraose and sialyllacto-N-neotetraose epimer

• Dirk Schmidt and
• Joachim Thiem

Beilstein J. Org. Chem. 2010, 6, No. 18, doi:10.3762/bjoc.6.18

• derivatives. Keywords: block synthesis; human milk oligosaccharides; sialyllacto-N-neotetraose epimer; sialyllacto-N-tetraose; trisaccharide thioglycoside donors; Introduction From an inspection of contemporary syntheses of biologically and medicinally relevant oligosaccharides, it is evident that the

• chemoenzymatic syntheses have been reported [1][2][3][4]. As a proof of principle, we were interested to employ some trisaccharide building units previously obtained by enzymatic routes in block syntheses en route to interesting structures. To this end, two human milk pentasaccharides of prominent importance

• has been reported in which sialylation with recombinant transsialidase (Trypanosoma cruzi) gave the trisaccharide 3 in 32% yield [8]. Treatment of 3 with methanol and acidic ion exchange resin led to the methyl ester (for the method cf. lit. [9]) which was then peracetylated to give trisaccharide 4 as

Convergent syntheses of Le^X analogues

• An Wang,
• Jenifer Hendel and
• France-Isabelle Auzanneau

Beilstein J. Org. Chem. 2010, 6, No. 17, doi:10.3762/bjoc.6.17

• An Wang Jenifer Hendel France-Isabelle Auzanneau Department of Chemistry, University of Guelph, Guelph, Ontario, N1G 2W1, Canada 10.3762/bjoc.6.17 Abstract The synthesis of three Lex derivatives from one common protected trisaccharide is reported. These analogues will be used respectively for

• carried a 6-chlorohexyl rather than a 6-azidohexyl aglycon. The 6-chlorohexyl disaccharide was then converted to an acceptor and submitted to fucosylation yielding the corresponding protected 6-chlorohexyl Lex trisaccharide. This protected trisaccharide was used as a precursor to the 6-azidohexyl, 6

• -acetylthiohexyl and 6-benzylthiohexyl trisaccharide analogues which were obtained in excellent yields (70–95%). In turn, we describe the deprotection of these intermediates in one single step using dissolving metal conditions. Under these conditions, the 6-chlorohexyl and 6-azidohexyl intermediates led