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

• 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

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• of the putative tetracenomycin-like intermediate 210, the aldehyde 211 is reduced to the corresponding alcohol 212. Acetalization and introduction of the 1,2-cis-diol moiety furnishes 213. Sequential formation of the lactone and the isoindolinone generates 214. A final glycosylation step leads to

• diastereoselective synthesis of lactonamycinone (214) employing a Diels–Alder reaction [162][163]. In 2010, Tastuta completed the first total synthesis of lactonamycin (215) by using a sequential conjugate addition, a stereoselective glycosylation reaction and a Michael–Dieckmann-type cyclization [164]. The recently

• published total synthesis of lactonamycin (215) and lactonamycin Z (217) by Saikawa and Nakata is based on a late-stage glycosylation strategy (Scheme 29). This enables the specific variation of the sugar components and gives access to various lactonamycin derivatives [161]. Starting from alcohol 219, the

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

• . Keywords: glycosylation; mucin-type oligosaccharides; O-glycans; oligosaccharide synthesis; Introduction Mucins are heavily glycosylated glycoproteins that may be membrane-associated or secreted in gel form and play an important biological role in the respiratory and intestinal tracks [1][2][3]. Mucins

• help us understand the biological and disease implications of these glycosylation patterns at both molecular and functional levels. However, despite the need for functional studies of O-glycosylation patterns, there are comparatively few reported syntheses leading to the basic mucin-type cores [9][10

• versatile blockwise strategy was employed to prepare targets 2–4, whereby each glycosylation product yielded compounds that were either deprotected to give the final products or became the acceptor for the next glycosylation step. The synthesis started from orthogonally protected 3-chloropropyl-α-linked

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

• achieved following a sequential glycosylation strategy. A minimum number of steps was used for the synthesis of the target compound involving a one-pot glycosylation and a protecting group manipulation. All intermediate reactions afford their products in high yield, and the glycosylation steps are

• stereoselective. Keywords: Escherichia coli; glycosylation; lipopolysaccharide; O-antigen; tetrasaccharide; Introduction Neonatal meningitis is a serious concern in developing countries [1]. The symptoms associated with this disease are unspecific and may ultimately lead to sepsis [2]. The common cause of the

• presented herein (Figure 2). Results and Discussion The target tetrasaccharide as its p-methoxyphenyl (PMP) glycoside was synthesized following a sequential glycosylation approach from the suitably functionalized monosaccharide intermediates 2 [13], 3 [14], 4 [15] and 5 [16]. These monosaccharide

Appel-reagent-mediated transformation of glycosyl hemiacetal derivatives into thioglycosides and glycosyl thiols

• Tamashree Ghosh,
• Abhishek Santra and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 974–982, doi:10.3762/bjoc.9.112

• carbonotrithioate. The reaction conditions are reasonably simple and yields were very good. Keywords: Appel reagent; carbon tetrabromide; glycosyl hemiacetal; glycosyl thiol; thioglycoside; triphenylphosphine; Introduction Thioglycosides (1-thiosugar) are widely used glycosyl donors in glycosylation reactions [1

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

• 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

• , H2 and I isolated from C. tubulosa thereby exploiting newly developed regio- and stereoselective glycosylation conditions (Figure 1). This straightforward synthetic strategy employs a minimum number of steps. Results and Discussion The target trisaccharide 1 in the form of its 2-phenylethyl glycoside

• presence of molecular iodine [13] furnished compound 5 in 86% yield. Regioselective 3-O-glycosylation of compound 5 with L-rhamnose derived trichloroacetimidate derivative 3 [11] in the presence of NOBF4 [14] followed by acetylation in the same pot furnished disaccharide derivative 6 in 76% yield. In this

De novo synthesis of D- and L-fucosamine containing disaccharides

• Daniele Leonori and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 332–341, doi:10.3762/bjoc.9.38

• influenced by their glycosylation patterns [1][2]. Therefore, an understanding of protein glycosylation is of utmost importance in order to develop new therapeutics [3][4][5][6]. The ability of bacteria to colonize human hosts and cause diseases is directly influenced by their capacity to synthesize

• microarray platform and their conjugation to carrier proteins, an appropriate linker was required at the anomeric position [67]. Placement of a C3 naphthyl ether anticipated the site for further glycosylation at this position, which typically serves as the connection to the next sugar. Therefore, building

• block 8a is ideal in terms of orthogonality and chemical synthesis. Hence, we tested the ability of D-8a to undergo anomeric functionalization and to effect glycosylation at the C3 hydroxy group. Due to the presence of N-acetylated D- and L-fucosamine residues in P. aeruginosa O-linked glycans, the

Synthesis and testing of the first azobenzene mannobioside as photoswitchable ligand for the bacterial lectin FimH

• Vijayanand Chandrasekaran,
• Katharina Kolbe,
• Femke Beiroth and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2013, 9, 223–233, doi:10.3762/bjoc.9.26

• , glycosylation of the key intermediate 10 by using the mannosyl donor 3 gave the desired mannobioside 11 in 76% yield. Finally, removal of the O-acetyl groups according to Zemplén led to the unprotected 1,3-linked target mannobioside α-D-Man-(1→3)-D-Man (2). With the two azobenzene glycosides 6 and 2 at hand

• , open-gate conformation). Bottom: (Z)-isomer (C, closed-gate; D, open-gate conformation). Synthesis of azobenzene mannoside 6 and azobenzene mannobioside 2 by glycosylation. Characterisation of the (E)- and (Z)-isomers of azobenzene glycosides 6 and 2. Inhibition of adhesion of E. coli to a mannan

Efficient synthesis of phenylene-ethynylene rods and their use as rigid spacers in divalent inhibitors

• Francesca Pertici,
• Norbert Varga,
• Arnoud van Duijn,
• Matias Rey-Carrizo,
• Anna Bernardi and
• Roland J. Pieters

Beilstein J. Org. Chem. 2013, 9, 215–222, doi:10.3762/bjoc.9.25

• rigid linkages between functional units. Examples of these have been reported in areas such as nanoelectronics and nanooptics [1], surfactants [2][3][4], photoelectrochemical detection [5], catalysis [6], glycosylation reactions [7], and carbohydrate–protein interactions [8]. Many different strategies

A new synthetic access to 2-N-(glycosyl)thiosemicarbazides from 3-N-(glycosyl)oxadiazolinethiones and the regioselectivity of the glycosylation of their oxadiazolinethione precursors

• El Sayed H. El Ashry,
• El Sayed H. El Tamany,
• Mohy El Din Abdel Fattah,
• Mohamed R. E. Aly,
• Ahmed T. A. Boraei and
• Axel Duerkop

Beilstein J. Org. Chem. 2013, 9, 135–146, doi:10.3762/bjoc.9.16

Glycosylation efficiencies on different solid supports using a hydrogenolysis-labile linker

• Mayeul Collot,
• Steffen Eller,
• Markus Weishaupt and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 97–105, doi:10.3762/bjoc.9.13

• /bjoc.9.13 Abstract Automated oligosaccharide assembly requires suitable linkers to connect the first monosaccharide to a solid support. A new hydrogenolysis-labile linker that is stable under both acidic and basic conditions was designed, synthesized and coupled to different resins. Glycosylation and

• cleavage efficiencies on these functionalized solid supports were investigated, and restrictions for the choice of solid support for oligosaccharide synthesis were found. Keywords: glycosylation; hydrogenolysis; linkers; oligosaccharides; resins; solid-phase synthesis; Findings Since Bruce Merrifield

• ][22][23]. It was early on recognized that the linker plays a pivotal role for oligosaccharide synthesis, as its chemical properties determine the conditions that can be used for glycosylation and deprotection reactions [7][20][23][24][25]. Equally important is the choice of solid support and many

Peptoids and polyamines going sweet: Modular synthesis of glycosylated peptoids and polyamines using click chemistry

• Daniel Fürniss,
• Timo Mack,
• Frank Hahn,
• Sidonie B. L. Vollrath,
• Katarzyna Koroniak,
• Ute Schepers and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 56–63, doi:10.3762/bjoc.9.7

• fast methods for the decoration of biomimetic molecules with sugars is of fundamental importance. The glycosylation of peptoids and polyamines as examples of such biomimetic molecules is reported here. The method uses Cu-catalyzed azide alkyne cycloaddition to promote the reaction of azidosugars with

• copper ions. In some cases, changing the base from DIPEA to DBU was beneficial (Scheme 2). After these encouraging results, we turned our attention to peptoids. For the glycosylation of peptoids, we envisaged the generation of a fully glycosylated peptoid in order to investigate the compatibility of

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

• synthesis of α-D-Galf-(1→2)-D-galactose by the same glycosylaldonolactone approach [25]. The same derivative 4 was envisaged as precursor of 1 due to the high regioselectivity previously achieved in glycosylation at HO-2. Additionally, this procedure would afford derivative 8, a valuable intermediate for

• in Et2O, employing TMSOTf as catalyst, proceeded with complete regio- and stereoselectivity, affording the α-glycosylaldonolactone 5 in 79% yield (Scheme 1). The α-anomeric configuration and the regioselectivity of the glycosylation were confirmed on the basis of the NMR spectra. In the 1H NMR

• into an apparent triplet. On the other hand, in the 13C NMR spectrum of 5 the signal corresponding to C-1 appeared at δ 170.1, shifted 4 ppm in comparison with the corresponding signal of 4, as result of glycosylation at the vicinal position [28]. For the reduction of the lactone function, compound 5

Acylsulfonamide safety-catch linker: promise and limitations for solid–phase oligosaccharide synthesis

• Jian Yin,
• Steffen Eller,
• Mayeul Collot and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 2067–2071, doi:10.3762/bjoc.8.232

• cleavage products revealed shortcomings for oligosaccharide synthesis. Keywords: glycosaminoglycans (GAGs); glycosylation; resins; safety-catch linker; solid-phase synthesis; Findings Solid-phase oligosaccharide synthesis [1][2] has been automated [3][4][5] to rapidly assemble complex oligosaccharides

• . In the process of evaluating the performance of this linker in solid-phase glycosylation reactions, the potential as well as some severe limitations became apparent. Linker 10 is the newly designed acylsulfonamide safety-catch linker (Scheme 1). The safety-catch linkage to the resin permits

• acylsulfonamide safety-catch linker 10 plus the Zemplén cleavage site, were employed in glycosylation reactions on a solid phase using an automated synthesizer [13], subsequently cleaved with NaOMe, and the products were analyzed by HPLC (Scheme 3, see Supporting Information File 1). Glycosylations were performed

Convergent synthesis of the tetrasaccharide repeating unit of the cell wall lipopolysaccharide of Escherichia coli O40

• Abhijit Sau and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2012, 8, 2053–2059, doi:10.3762/bjoc.8.230

• using a convergent block glycosylation strategy. A disaccharide donor was coupled to a disaccharide acceptor by a stereoselective glycosylation. A 2-aminoethyl linker was chosen as the anomeric protecting group at the reducing end of the tetrasaccharide. All glycosylation steps are significantly high

• yielding and stereoselective. Keywords: Escherichia coli; glycosylation; lipopolysaccharide; O-antigen; tetrasaccharide; Introduction Infantile diarrhoea is one of the major causes of morbidity and mortality in infancy in developing countries [1]. Among several factors, Escherichia coli (E. coli

• strategy. Results and Discussion The target tetrasaccharide 1 as its 2-aminoethyl glycoside was synthesized by a stereoselective glycosylation of a disaccharide acceptor 8 and a disaccharide thioglycoside donor 9 using a [2 + 2] block synthetic strategy. The disaccharide intermediates were synthesized from

Antifreeze glycopeptide diastereomers

• Lilly Nagel,
• Carsten Budke,
• Axel Dreyer,
• Thomas Koop and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 1657–1667, doi:10.3762/bjoc.8.190

• polyproline helix type II (PPII) [13]. The larger AFGP1-4 are known to form flexible rods with segmental mobility [14][15]. Recent research has been directed toward the assembly of synthetic AFGPs with tailored amino acid composition and glycosylation pattern. The main target is to investigate the influence

• recrystallization assays. The glycosylation of threonine in D- and allo-L-configuration with N-acetyl galactosamine relies on an efficient synthetic procedure by Paulsen et al. [21] adapted by us [16][22][23] (Scheme 1). Azidochlorination of a suitably protected L-galactal provides the peracetylated 2-azido-2

• -desoxygalactopyranosyl chloride serving as a glycosyl donor in a silver-mediated Koenigs–Knorr glycosylation of the particular Fmoc- and t-Bu-protected amino acids, i.e., the allo-L-configured (1A) and D-configured (1B) threonine derivatives. Both glycosylated amino acids (2) were obtained in good yields and very good

The Amadori rearrangement as glycoconjugation method: Synthesis of non-natural C-glycosyl type glycoconjugates

• Katharina Gallas,
• Gerit Pototschnig,
• Florian Adanitsch,
• Arnold E. Stütz and
• Tanja M. Wrodnigg

Beilstein J. Org. Chem. 2012, 8, 1619–1629, doi:10.3762/bjoc.8.185

• chemistry (Huisgen cycloaddition) [4][5], glycosylation protocols [6][7], and Staudinger ligation [8], just to mention the most prominent examples. However, many applications in this respect require a ligation method that is functional in aqueous medium, and, for economic purposes in general, protecting

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

• this important class of molecules. The automated synthesis of oligosaccharides has been significantly improved since the first report in 2001 [4]. Currently, the platform enables the rapid assembly of complex oligosaccharides and accommodates the most commonly employed glycosylation reactions [5][6][7

• the glycosylation of building blocks 1, 8 and 10 with galactal 2 under similar conditions (Table 1, entries 1–3). Sialylation with building block 8 failed to yield any disaccharide 9 (Table 1, entry 1), while glycosylating agents 10 and 1 gave moderate yields and good selectivity (Table 1, entries 2

• and 3). The glycosylation of galactal 2 with phosphite 1, which we described in the supporting information of [5], was further optimized. In particular, elevating the reaction temperature proved beneficial and disaccharide 9 was isolated in higher overall yield, albeit with a slight decrease in

Studies on the substrate specificity of a GDP-mannose pyrophosphorylase from Salmonella enterica

• Lu Zou,
• Ruixiang Blake Zheng and
• Todd L. Lowary

Beilstein J. Org. Chem. 2012, 8, 1219–1226, doi:10.3762/bjoc.8.136

• -benzylidene-α-D-mannopyranoside (19) [26] was first methylated giving 20 and then converted into glycosyl acetate 21 in 49% yield over the two steps. Subsequent thioglycosylation provided a 52% yield of 22. The protected dibenzyl phosphate 23 was next formed by the NIS–AgOTf promoted glycosylation of dibenzyl

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

• is modified at O-4 as a methyloxy, deoxychloro or deoxyfluoro, were synthesized. We first report the preparation of the modified 4-OMe, 4-Cl and 4-F trichloroacetimidate galactosyl donors and then report their use in the glycosylation of an N-acetylglucosamine glycosyl acceptor. Thus, we observed

• that the reactivity of these donors towards the BF3·OEt2-promoted glycosylation at O-4 of the N-acetylglucosamine glycosyl acceptors followed the ranking 4-F > 4-OAc ≈ 4-OMe > 4-Cl. The resulting disaccharides were deprotected at O-3 of the glucosamine residue and fucosylated, giving access to the

• toward glycosylation [64][65][66]. However, we have reported the successful O-4 glycosylation of an N-acetylglucosamine monosaccharide acceptor using peracetylated gluco- and galactopyranose α-trichloroacetimidate donors under activation with 2 equivalents of BF3·OEt2 at room temperature or 40 °C [14][67

Synthesis and structure of tricarbonyl(η⁶-arene)chromium complexes of phenyl and benzyl D-glycopyranosides

• Thomas Ziegler and
• Ulrich Heber

Beilstein J. Org. Chem. 2012, 8, 1059–1070, doi:10.3762/bjoc.8.118

• reacting acetobromoglucose with 6-tert-butyl-2-hydroxypyridine [20] under Helferich conditions (Hg(CN)2). Only the corresponding O-glycoside 1l was obtained, and no N-glycoside was formed in this Helferich glycosylation (Scheme 1). Sterically hindered 6-tert-butyl-2-hydroxypyridine was chosen as the

• . Treatment of pentaacetylglucose and 2-tert-butylphenol with BF3-etherate in dichloromethane afforded 1o in 31% yield. Glycoside 1p was prepared by a Helferich glycosylation of o-methylbenzyl alcohol with acetobromoglucose. For further details see Supporting Information File 1. Table 2 summarizes the results

The use of glycoinformatics in glycochemistry

• Thomas Lütteke

Beilstein J. Org. Chem. 2012, 8, 915–929, doi:10.3762/bjoc.8.104

• that it provides information on proteins to which specific glycans were found to be attached, including details on glycosylation sites. The Japan Consortium for Glycobiology and Glycotechnology DataBase (JCGGDB) [34] provides a collection of individual databases that are cross-linked with each other

• used to create models of carbohydrate chains. The latter program can also perform in silico glycosylation by adding the glycan chains to a protein 3D structure, and provides input files for the AMBER [94][95] modeling programs using the GLYCAM force field [99]. Glycan 3D structures calculated by Sweet

• CHARMM [97] input files from PDB files that contain carbohydrates. Various tools to predict the occupancy state of potential glycosylation sites from protein sequence data are available as well (Table 5). If a protein–carbohydrate complex is to be modeled, generally available docking tools such as

Synthetic glycopeptides and glycoproteins with applications in biological research

• Ulrika Westerlind

Beilstein J. Org. Chem. 2012, 8, 804–818, doi:10.3762/bjoc.8.90

• -tuning of native chemical ligation (NCL), expressed protein ligation (EPL), and chemoenzymatic glycosylation techniques have all together enabled the synthesis of functional glycoproteins. The synthesis of structurally defined, complex glycopeptides or glyco-clusters presented on natural peptide

• glycosylation sites, is valuable for functional biological studies. Glycopeptides have, for instance, been applied to evaluate the role of conformational and proteolytic stability [6]. In other studies, synthetic glycopeptides have been employed in vaccines to induce specific immune responses or for the

• the discovery, by Springer et al., that glycoproteins on the outer cell membrane of epithelial tumor cells have an altered glycosylation consisting of the Thomsen-Friedenreich (T-) antigen and its precursor TN-antigen structure, the synthesis and evaluation of anti-tumor vaccines have been a topic of

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

• Grazia Marano,
• Claas Gronewold,
• Martin Frank,
• Anette Merling,
• Christian Kliem,
• Sandra Sauer,
• Manfred Wiessler,
• Eva Frei and
• Reinhard Schwartz-Albiez

Beilstein J. Org. Chem. 2012, 8, 787–803, doi:10.3762/bjoc.8.89

• among cells are mediated by binding of proteins such as lectins to oligosaccharides. Upon progression to higher malignancy, the glycosylation patterns of glycoproteins and glycosphingolipids on tumor cell surfaces undergo several alterations [6]. These changes are closely associated with distinct

• cellular processes, such as adhesion to the ECM, and modulation of the tumor-associated microenvironment, which represent advantages for the capacity of the cell to invade the host tissue and to secure undisturbed growth [7]. The glycosylation pattern of tumor cells is therefore the focus in the

• , represents a strong candidate for the design of saccharide mimetics to be used as anti-tumor drugs. Results and Discussion Syntheses of saccharide mimetics Glycosylation of 3,4-bis(hydroxymethyl)furan (1) with 1.0 equiv imidate 2 in CH2Cl2 afforded 48% of monosaccharide 3. The synthesis of (4-{[(β-D

Synthesis and antifungal properties of papulacandin derivatives

• Marjolein van der Kaaden,
• Eefjan Breukink and
• Roland J. Pieters

Beilstein J. Org. Chem. 2012, 8, 732–737, doi:10.3762/bjoc.8.82

• glycal 18, led us to compound 37. This compound opens the way to a total synthesis of disaccharides such as the papulacandins A–C. Selective protection of the hydroxy group of C(6) followed by glycosylation of the hydroxy group at C(4), should accomplish this. In our biological assay we did not see any