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

• hydrophilic than simple sugars. We have been developing pseudo-disaccharide molecules such as 23 [32] (Scheme 7) as mimics of mannose disaccharides for the interaction with DC-SIGN and other C-lectins [33][34][35]. This molecule and its derivatives [36] contain lipophilic moieties that generally increase

S-Fluorenylmethyl protection of the cysteine side chain upon N^α-Fmoc deprotection

• Johannes W. Wehner and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2012, 8, 2149–2155, doi:10.3762/bjoc.8.242

• methods, NCL or SPPS. In addition, mannosidic glycoamino acids are of interest as ligands for mannose-specific lectins in solution [17] as well as for the fabrication of glycoarrays on solid support [10][18][19]. Moreover, we are interested to advance glycoamino acid deriatives such as 3 into ligands that

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

• HPAEC–PAD Varianose was isolated from a culture of Penicillium varians [3] and its identity was proved by methylation and GLC–MS analysis. D-Galactose, D-mannose and D-glucose in the ratio 70:15:15 and the corresponding diagnostic peaks for the methylated sugars were observed, as previously described [4

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

• method in hand, D-galactose (14), D-mannose (17) as well as GlcNAc (20) were successfully converted to the corresponding aldoheptoses (Scheme 4), namely D-glycero-L-manno/L-gluco-heptopyranose 16a and 16b, D-glycero-D-galacto/D-talo-heptopyranose 19a and 19b, and 3-acetamido-3-deoxy-D-gluco-D-ido/D-gulo

• )-1-deoxy-α-D-manno-hept-2-ulopyranose (28): General method for sugar elongation was applied to D-mannose 17 (3 g, 16.7 mmol), pyridine (50 mL), triethylamine (0.18 mL, 1.3 mmol, 0.08 equiv) and HCN (4.5 mL, 0.11 mmol, 6.9 equiv). After five days, complete consumption of the aldose was indicated by

• ; found: C, 51.16; H, 8.06. Amadori rearrangement. C-Elongation using the sodium cyanide/sodium borohydride and HCN/Pd(BaSO4) method. C-Elongation as well as Amadori rearrangement in the D-gluco series. C-Elongation method by modified Kiliani–Fischer protocol from of D-galactose, D-mannose as well as

Mannose-decorated cyclodextrin vesicles: The interplay of multivalency and surface density in lectin–carbohydrate recognition

• Ulrike Kauscher and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2012, 8, 1543–1551, doi:10.3762/bjoc.8.175

• be modified by host–guest interactions with functional guest molecules. In this article, we investigate the multivalent interaction of the lectin concanavalin A (ConA) with cyclodextrin vesicles decorated with mannose–adamantane conjugates with one, two or three adamantane units as well as one or two

• mannose units. The carbohydrate–lectin interaction in this artificial, self-assembled glycocalyx was monitored in an agglutination assay by the increase of optical density at 400 nm. It was found that there is a close relation between the carbohydrate density at the cyclodextrin vesicle surface and the

• multivalent interaction with ConA, and the most efficient interaction (i.e., fastest agglutination at lowest concentration) was observed for mannose–adamantane conjugates, in which both the cyclodextrin–adamantane and the lectin–mannose interaction is inherently multivalent. Keywords: carbohydrates

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

• strategy for the synthesis of these compounds, we chose to take advantage of a GDP-mannose pyrophosphorylase (GDP-ManPP) from Salmonella enterica [23], which had previously been shown to have a relaxed specificity for the sugar 1-phosphate moiety [24][25]. In particular, it has been shown that the enzyme

• deprotection. Synthesis of 6-methoxy derivative 12 Two routes, differing in the choice of protecting groups, were explored to produce the 6-methoxy Manp-1P derivative 12 (Scheme 4 and Scheme 5). In one route, the C-2, C-3, and C-4 hydroxy groups of the mannose residues were protected with benzyl ethers and in

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

• purchased from several companies. In general, however, electron-donating protecting groups in the sugar moiety accelerated the formation of the chromium complexes at the aglycon (Table 1, entries 3 and 4). Treatment of the mannose orthoester 1f (Table 1, entry 6) under the standard conditions applied here

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

• glycopeptide/glycoprotein synthesis, Endo-A specific for high-mannose glycans and Endo-M operating on both high-mannose and complex type N-glycans [81][82][83]. These enzymes can, in contrast to glycosyltransferases, by means of a one-step reaction attach large oligosaccharides to a GlcNAc polypeptide. Until

• glycoprotein are a few examples [84][86][87][88][89]. The glycan remodeling approach is particularly interesting for glycoprotein synthesis. This method was employed in the synthesis of two RNase B glycoproteins modified with either high-mannose or complex type N-glycans [87]. The bovine RNase B glycoprotein

• 39 used in this study contained a mixture of high-mannose glycoforms; by treatment with endoglycosidase H (Endo-H), these glycans could be hydrolytically cleaved leaving the GlcNAc monosaccharide still attached to the protein. By treatment with a complex type glycan oxazoline donor and an Endo-M

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

• [25] created a β-D-mannose-containing inhibitor of α4β1 based on in silico modeled structures. In silico analysis of GSF interaction with integrins Our data showing similar inhibition of melanoma cell attachment to fibronectin by GSF as by the combined integrin ligand peptides, also points to an

• siRNA inhibition of the fucosyltransferase FUT1 and GDP-4-keto-6-deoxymannose-epimerase/reductase (FX-protein) [19]. The FX-protein is required for de novo synthesis of GDP-fucose from GDP-mannose [46], whereas FUT 1 catalyzes the α2 fucosylation of blood group H type 1 and Lewisy oligosaccharides. The

Facile synthesis of nitrophenyl 2-acetamido-2-deoxy-α-D-mannopyranosides from ManNAc-oxazoline

• Karel Křenek,
• Petr Šimon,
• Lenka Weignerová,
• Barbora Fliedrová,
• Marek Kuzma and
• Vladimír Křen

Beilstein J. Org. Chem. 2012, 8, 428–432, doi:10.3762/bjoc.8.48

• from Sigma-Aldrich, except for 2-acetamido-2-deoxy-D-mannose, which was purchased from BIOSYNTH AG, Staad, CH. The reactions were monitored by TLC with precoated silica gel 60 F254 aluminium sheets from Merck, detected with UV light and/or charred with sulfuric acid (5% in EtOH). The compounds were

Coupled chemo(enzymatic) reactions in continuous flow

• Ruslan Yuryev,
• Simon Strompen and
• Andreas Liese

Beilstein J. Org. Chem. 2011, 7, 1449–1467, doi:10.3762/bjoc.7.169

• developing a continuous enzymatic production of GDP-mannose 43 from mannose 1-phosphate (40) using GDP-mannose pyrophosphorylase (Scheme 13), Fey and co-workers encountered a two-fold product inhibition of the enzyme by both products 43 and pyrophosphate 41, which deteriorated production performance [36

• decarboxylase; E2: RecLb-alcohol dehydrogenase; E3: Formate dehydrogenase [2]. Production of a dipeptide 39 in a cascade of two continuously operated membrane reactors. E1: Carboxypeptidase Y; E2: Peptide amidase [35]. Continuous production of GDP-mannose (43) from mannose 1-phosphate (40) in a cascade of two

• enzyme membrane reactors. E1: GDP-mannose pyrophosphorylase; E2: Pyrophosphatase [36]. Continuous solvent-free chemo-enzymatic synthesis of ethyl (S)-3-(benzylamino)butanoate (48) in a sequence of a plug-flow reactor (PFR) and a packed-bed reactor containing Novozym 435 (E) [38]. Continuous chemo

Amine-linked diglycosides: Synthesis facilitated by the enhanced reactivity of allylic electrophiles, and glycosidase inhibition assays

• Ian Cumpstey,
• Jens Frigell,
• Elias Pershagen,
• Tashfeen Akhtar,
• Elena Moreno-Clavijo,
• Inmaculada Robina,
• Dominic S. Alonzi and
• Terry D. Butters

Beilstein J. Org. Chem. 2011, 7, 1115–1123, doi:10.3762/bjoc.7.128

• the pseudodisaccharide 10 in high yield (Scheme 3). The alcohol 1 also underwent similar coupling with the glucose-6-triflamide 7 and the mannose-6-nosylamide 9 under the same Mitsunobu conditions to give the respective diglycoside precursors 11 and 12 in excellent yields. These were the same reaction

• biosynthesis of N-linked glycoproteins: Glc(α1→3)Glc and Glc(α1→3)Man. The Alt(N2–6)Man structure does not bear an immediately obvious resemblance to either of these substructures. Moreover, it has been proposed that a mannose-binding lectin domain of the α-glucosidase II β-subunit is also important for its

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• [70] to prepare 5-des(hydroxymethyl)-1-deoxynojirimycin (114) and its mannose analogue 111 (as HCl salts) in a highly stereoselective mode starting from a different common olefin, 107 (Scheme 20). In this case, RCM was promoted by the 2nd-generation Grubbs catalyst 5 which ensured a high yield of the

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

• agent of tuberculosis (TB), possesses a complex cell wall containing mannose-rich glycophospholids termed phosphatidylinositol mannosides (PIMs), lipomannan (LM), and lipoarabinomannan (LAM). These glycophospholipids play important roles in cell wall function and host–pathogen interactions. Synthetic

• PIM/LM/LAM substructures are useful biochemical tools to delineate and dissect the fine details of mannose glycophospholipid biosynthesis and their interactions with host cells. We report the efficient synthesis of a series of azidooctyl di- and trimannosides possessing the following glycan structures

• biosynthesis commences with the stepwise transfer of two mannosyl residues onto inositol, catalyzed by the GDP-mannose dependent α-mannosyltransferases PimA [11] and PimB' [12][13], followed by acylation by the acyltransferase (Rv2611c) to give AcPIM2 [14][15]. Additional α-1,6-mannosylations of AcPIM2 give

The allylic chalcogen effect in olefin metathesis

• Yuya A. Lin and
• Benjamin G. Davis

Beilstein J. Org. Chem. 2010, 6, 1219–1228, doi:10.3762/bjoc.6.140

• GlcNAc, mannose and N-acetylamine, which could serve as effective mimics of post-translational protein modifications (glycosylation, lysine acetylation). Conclusion Since the early work by Hoye on secondary allylic alcohols [19] and later the studies on allyl sulfides by our group [17], the allyl

Carbasugar analogues of galactofuranosides: α-O-linked derivatives

• Jens Frigell and
• Ian Cumpstey

Beilstein J. Org. Chem. 2010, 6, 1127–1131, doi:10.3762/bjoc.6.129

• electronically favoured) to give 1,2-trans-diaxial [11] carba-α-mannose derivatives with both oxygen [12] and nitrogen [13] nucleophiles. The electronic argument must be reformulated slightly in the absence of a Lewis acid. The localisation of electrons onto the leaving group (the epoxide oxygen) is necessary as

• attack at C2 in the epoxide opening and formation of a β-galacto product. We then examined a secondary carbohydrate alcohol as the nucleophile. The mannose OH-3 nucleophile 10 [24] would lead to a structure corresponding to a Galf(α1→3)Manp disaccharide substructure from the galactomannan from the fungus

En route to photoaffinity labeling of the bacterial lectin FimH

• Thisbe K. Lindhorst,
• Michaela Märten,
• Andreas Fuchs and
• Stefan D. Knight

Beilstein J. Org. Chem. 2010, 6, 810–822, doi:10.3762/bjoc.6.91

• , Uppsala Biomedical Center, SE-75124 Uppsala, Sweden 10.3762/bjoc.6.91 Abstract Mannose-specific adhesion of Escherichia coli bacteria to cell surfaces, the cause of various infections, is mediated by a fimbrial lectin, called FimH. X-ray studies have revealed a carbohydrate recognition domain (CRD) on

• FimH that can complex α-D-mannosides. However, as the precise nature of the ligand–receptor interactions in mannose-specific adhesion is not yet fully understood, it is of interest to identify carbohydrate recognition domains on the fimbrial lectin also in solution. Photoaffinity labeling serves as an

• insertion reaction could be solved by MS/MS studies. Furthermore, photoaffinity-labeling of FimHtr was successful and could be demonstrated by mass spectrometric studies as well as dot–blot analysis. The overall goal of this study is to identify mannose binding sites on the bacterial lectin FimH in solution

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

• Thisbe K. Lindhorst Kathrin Bruegge Andreas Fuchs Oliver Sperling Christiana Albertina University of Kiel, Otto Diels Institute of Organic Chemistry, Otto-Hahn-Platz 4, D-24098 Kiel, Germany, Fax: +49 431 8807410 10.3762/bjoc.6.90 Abstract FimH is a mannose-specific bacterial lectin found on type

• surface of many bacteria, comprising carbohydrate-binding sub-units [4][5][6]. The type 1 fimbriae, for example, which are widely spread among the Enterobacteriaceae are terminated with the mannose-specific protein FimH. FimH is structured in the form of two domains, a carbohydrate-specific adhesin domain

• -mannosyl moiety, for example, the terminal mannoside residues of high-mannose-type glycoproteins of the glycocalyx [12]. However, the precise nature of the ligand-receptor interactions is not fully understood. For example, when multivalent carbohydrate ligands were tested as ligands of FimH and type 1

New amphiphilic glycopolymers by click functionalization of random copolymers – application to the colloidal stabilisation of polymer nanoparticles and their interaction with concanavalin A lectin

• Otman Otman,
• Paul Boullanger,
• Eric Drockenmuller and
• Thierry Hamaide

Beilstein J. Org. Chem. 2010, 6, No. 58, doi:10.3762/bjoc.6.58

• et Supramoléculaires (ICBMS), Chimie Organique 2 – Glycochimie, UMR CNRS 5246, CPE-Lyon. 43, boulevard du 11 Novembre 1918, Villeurbanne, F-69622, France 10.3762/bjoc.6.58 Abstract Glycopolymers with mannose units were readily prepared by click chemistry of an azido mannopyranoside derivative and a

• Pluronic® F-68. The mannose moieties are accessible at the surface of nanoparticles and available for molecular recognition by concanavalin A lectin. Interaction of mannose units with the lectin were evaluated by measuring the changes in nanoparticles size by dynamic light scattering in dilute media

• [1] whilst mannose units can be used for nerve cells targeting [2]. Besides naturally occurring polysaccharides, macromolecular engineering allows quite interesting possibilities for modelling of synthetic glycopolymers [3]. The hydrophobic component can be introduced by any convenient polymer moiety

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

• José L. Jiménez Blanco,
• Fernando Ortega-Caballero,
• Carmen Ortiz Mellet and
• José M. García Fernández

Beilstein J. Org. Chem. 2010, 6, No. 20, doi:10.3762/bjoc.6.20

• units present, more so than is the case with other biomolecules such as polypeptides or oligonucleotides. This is determined by the stereochemical identity of the monosaccharide units present (e.g. glucose, galactose, mannose), their glycosidic linkage positions (e.g. 1→4, 1→6), the nature at anomeric

• -oligomers of mannose- and glucose-derived furanoid SAAs [58] in order to constrain their conformational degrees of freedom and to induce desirable structural elements essential for their biological activities, such as tubular structures for transporting ions or molecules across membranes. Detailed ROESY

Vinylogous Mukaiyama aldol reactions with 4-oxy-2-trimethylsilyloxypyrroles: relevance to castanospermine synthesis

• Roger Hunter,
• Sophie C. M. Rees-Jones and
• Hong Su

Beilstein J. Org. Chem. 2007, 3, No. 38, doi:10.1186/1860-5397-3-38

• early castanospermine syntheses were carbohydrate-based, and used glucose or mannose as their starting materials. However, in more recent times there has been a trend towards using other building blocks from the chiral pool to introduce some of the chiral centres.[23][24] Of these approaches, a number