Expanding the scope of cyclopropene reporters for the detection of metabolically engineered glycoproteins by Diels–Alder reactions

• Anne-Katrin Späte,
• Verena F. Schart,
• Julia Häfner,
• Andrea Niederwieser,
• Thomas U. Mayer and
• Valentin Wittmann

Beilstein J. Org. Chem. 2014, 10, 2235–2242, doi:10.3762/bjoc.10.232

• fact that it can be orthogonal to the azide–alkyne cycloaddition [22][26][27] which allows dual labeling of two different sugars within one experiment [19][21][23][24]. Among the dienophiles mentioned above, strained cyclopropenes have the highest reaction rates for DAinv reactions with tetrazines and

• sugars 1 and 2 we neutralized the corresponding hexosamine hydrochlorides 5 and 6 with sodium methoxide and coupled them to the activated cyclopropene 7 (Scheme 2), the synthesis of which we reported previously [24]. Subsequent acetylation of the carbamates 8 and 9 gave Ac4GlcNCyoc (1) and Ac4GalNCyoc (2

• ], followed by labeling with streptavidin–AlexaFluor647 (streptavidin–AF647) (Scheme 3). With all three sugars staining of the plasma membrane was detected by confocal laser scanning microscopy of living cells (Figure 2A, B, C). Only the solvent control did not show any membrane staining (Figure 2D, for

Indium-mediated allylation in carbohydrate synthesis: A short and efficient approach towards higher 2-acetamido-2-deoxy sugars

• Christopher Albler,
• Ralph Hollaus,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2014, 10, 2230–2234, doi:10.3762/bjoc.10.231

Reaction of selected carbohydrate aldehydes with benzylmagnesium halides: benzyl versus o-tolyl rearrangement

• Maroš Bella,
• Bohumil Steiner,
• Vratislav Langer and
• Miroslav Koóš

Beilstein J. Org. Chem. 2014, 10, 1942–1950, doi:10.3762/bjoc.10.202

• simple alkyl or aryl branched-chain sugars involves the addition of Grignard reagents. In this regard, a wide variety of Grignard reagents have been added to the free or masked (as hemiacetal) carbonyl functionalities present in the molecule of a suitable fully O-protected saccharide, thereby making

• ketones affording the corresponding hydantoins (precursors of amino acids) via the Bucherer–Bergs reaction in the next step, which were finally transformed into sugar amino acids (precursors of biologicaly active iminosugars). Thus, using methylmagnesium iodide, some alanine-branched sugars were obtained

Synthesis of a bifunctional cytidine derivative and its conjugation to RNA for in vitro selection of a cytidine deaminase ribozyme

• Nico Rublack and
• Sabine Müller

Beilstein J. Org. Chem. 2014, 10, 1906–1913, doi:10.3762/bjoc.10.198

• RNA catalysts that support an aldol reaction between an aldehyde and a ketone, relevant to the synthesis of sugars [6], or the linkage of ribose to nucleobases to generate nucleotides [7]. Such ribozymes are seen as important functional entities underscoring the RNA world theory, where ribonucleic

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• system (Scheme 27) [98][99]. Attempts to replace the aldehyde 73a with its 3,4,6-hydroxylated counterpart failed to give the expected product [99]. Dwivedi et al. showed that the isopropylidene-protected sugars 75 reacted efficiently with urea (or thiourea) and 1,3-dicarbonyl compounds in diethylene

Expedient synthesis of 1,6-anhydro-α-D-galactofuranose, a useful intermediate for glycobiological tools

• Luciana Baldoni and
• Carla Marino

Beilstein J. Org. Chem. 2014, 10, 1651–1656, doi:10.3762/bjoc.10.172

• ; Introduction Anhydro sugars are formed by the intramolecular elimination of a water molecule, with the simultaneous formation of a new heterocyclic ring of different size. They are valuable intermediates not only in carbohydrate synthesis, but also as starting materials for other natural and non-natural

• complex products and bioactive compounds. Among the glycosans, the anhydro sugars involving the anomeric center in the ring formation, the 1,6-anhydro sugars are the most common and useful building blocks [1][2]. They can play a role in synthetic methodologies aiming at the obtainment of regioselectively

• functionalized sugars in a few steps, which could give easy access to convenient glycosyl donors and acceptors [3]. Some sugars, for example galactose, can afford not only the pyranosic derivative 1 but also the furanosic 1,6-anhydro derivative 2, both of which may be equipped with [3.2.1] bicyclic skeletons

Photoswitchable precision glycooligomers and their lectin binding

• Daniela Ponader,
• Sinaida Igde,
• Marko Wehle,
• Katharina Märker,
• Mark Santer,
• David Bléger and
• Laura Hartmann

Beilstein J. Org. Chem. 2014, 10, 1603–1612, doi:10.3762/bjoc.10.166

• the Z-form only allows for a monovalent binding of one of the sugars to the protein receptor (Figure 3b). Such a change in binding mode is expected to lead to the observed decrease in binding affinity. It is important to note that additional binding modes might contribute to the multivalent binding of

The search for new amphiphiles: synthesis of a modular, high-throughput library

• George C. Feast,
• Thomas Lepitre,
• Xavier Mulet,
• Charlotte E. Conn,
• Oliver E. Hutt,
• G. Paul Savage and
• Calum J. Drummond

Beilstein J. Org. Chem. 2014, 10, 1578–1588, doi:10.3762/bjoc.10.163

• synthesise double and triple-chain amphiphiles. With tails in hand, attention was turned to the hydrophilic amphiphile head groups. Sugar head groups were selected for this library because sugars are popular drug targets; however, such compounds often suffer from poor bioavailability [39]. By loading such

• extensively reviewed [44][45][46][47][48][49][50]. Azido-sugars are known to react well under CuAAC reaction conditions [51][52] and have recently been used in the synthesis of a glycodendrimer library [53], as well as in our previous work on single-chain sugar amphiphiles [30]. Hence, a diverse sugar screen

• would provide a wealth of data on the appropriate characteristics for a self-assembled sugar-based amphiphilic drug. Five sugars were chosen for this library: glucose, galactose, lactose, xylose and mannose. Glucose and galactose amphiphiles have been demonstrated to possess slightly different lyotropic

Multivalent scaffolds induce galectin-3 aggregation into nanoparticles

• Candace K. Goodman,
• Mark L. Wolfenden,
• Pratima Nangia-Makker,
• Anna K. Michel,
• Avraham Raz and
• Mary J. Cloninger

Beilstein J. Org. Chem. 2014, 10, 1570–1577, doi:10.3762/bjoc.10.162

• functionalized dendrimers were characterized by MALDI–TOF–MS (matrix-assisted laser desorption time of flight mass spectrometry). The average numbers of sugars that were incorporated are shown in Scheme 2. The loadings were determined by both the changes in weight average molecular weight (Mw) upon addition of 1

• and the changes in Mw upon deacetylation, enabling characterization of the average number of sugars per dendrimer [30]. Additional characterization details (including 1H NMR spectra) are provided in Supporting Information File 1. Characterization of dendrimer/galectin-3 aggregates Dynamic light

Orthogonal dual thiol–chloroacetyl and thiol–ene couplings for the sequential one-pot assembly of heteroglycoclusters

• Michele Fiore,
• Gour Chand Daskhan,
• Baptiste Thomas and
• Olivier Renaudet

Beilstein J. Org. Chem. 2014, 10, 1557–1563, doi:10.3762/bjoc.10.160

• sugars. We demonstrate that the reaction sequence starting with TCC can be performed one-pot whereas the reverse sequence requires a purification step after the TEC reaction. The versatility of this orthogonal strategy has been demonstrated through the synthesis of diverse hGCs displaying alternating

• capitalized on the utilization of a core scaffold decorated with identical sugars which are covalently linked through various spacers. While mimicking the multivalent sugar display of biological systems, these structures poorly reflect their inherent heterogenicity which hampers progresses towards the

• in our group to prepare tetravalent structures displaying two sugars either in 2:2 or 3:1 relative proportions [20]. In the meanwhile, the group of A. Dondoni has developed a sequential orthogonal TEC in combination with CuAAC for grafting two different sugar motifs on calix[4]arene scaffold [21

Synthesis and solvodynamic diameter measurements of closely related mannodendrimers for the study of multivalent carbohydrate–protein interactions

• Yoann M. Chabre,
• Alex Papadopoulos,
• Alexandre A. Arnold and
• René Roy

Beilstein J. Org. Chem. 2014, 10, 1524–1535, doi:10.3762/bjoc.10.157

• supported by the recent findings that the sugar backbones themselves also possess a hydrophobic side that orients the sugars in appropriate aromatic amino acid rich pockets [26][27][28]. Unfortunately, due to the inherent complexity of studying multivalent binding interactions, researchers have used

• spectrum supported complete conversion. Note that working with peracetylated sugar precursors allows less tedious purification practices as opposed to working with unprotected sugars which often necessitate purification by cumbersome dialysis followed by HPLC treatment. Here again, the complete structural

Why a diaminopyrrolic tripodal receptor binds mannosides in acetonitrile but not in water?

• Diogo Vila-Viçosa,
• Oscar Francesconi and
• Miguel Machuqueiro

Beilstein J. Org. Chem. 2014, 10, 1513–1523, doi:10.3762/bjoc.10.156

• reason for the higher activity in this solvent. This work also presents a new implementation of the stochastic titration constant-pH molecular dynamics method to a synthetic receptor of sugars and attests its ability to describe the protonation/conformation coupling in these molecules. Keywords

• over the years [1][2][3][4][5][6]. Most of these were developed for glucose since it is one of the most common sugars in living systems [7] and the preferred monosaccharide for energy storage [8]. However, mannose is essential for various biological functions, such as molecular recognition, being one

• of the most abundant sugars in glycoconjugates [9][10]. In 2011, Roelens’ group [11][12][13] synthetized and tested a chiral diaminopyrrolic tripodal receptor that showed high binding affinities to mannosides (Figure 1). This particular receptor is significantly more active in acetonitrile (ACN) than

Postsynthetic functionalization of glycodendrons at the focal point

• Thisbe K. Lindhorst and
• Katharina Elsner

Beilstein J. Org. Chem. 2014, 10, 1482–1487, doi:10.3762/bjoc.10.152

• example the glycodendrimers, have become valuable tools during the last two decades [2]. Typical glycodendrimers consist of (hyper)branched dendritic core molecules which are decorated with specific sugars in their periphery [3][4][5]. In addition to dendrimers, also so-called dendrons have been

Multichromophoric sugar for fluorescence photoswitching

• Stéphane Maisonneuve,
• Rémi Métivier,
• Pei Yu,
• Keitaro Nakatani and
• Juan Xie

Beilstein J. Org. Chem. 2014, 10, 1471–1481, doi:10.3762/bjoc.10.151

• supramolecular systems. Only one artificial light-harvesting antenna system grafted on the α-D-glucopyranoside has been reported [17]. Results and Discussion Synthesis of multichromophoric sugars Synthesis of organic nano-architectures with a high degree of structural order and defined properties is challenging

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• steric effects [31]. The strategy is based on the finding that certain PEGylated nucleotide-sugars are effectively transferred to a glycan acceptor by the corresponding glycosyltransferase. A modified sialic acid PEGylated at the 5’-amino position in the CMP nucleotide (CMP-SA-5-NHCOCH2NHPEG) can be

Synthesis of a sucrose dimer with enone tether; a study on its functionalization

• Zbigniew Pakulski,
• Norbert Gajda,
• Magdalena Jawiczuk,
• Jadwiga Frelek,
• Piotr Cmoch and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2014, 10, 1246–1254, doi:10.3762/bjoc.10.124

• designed for such receptors, sugars are the most promising due to their availability and biocompatibility. Up to date only monosaccharides have found a wide application in the synthesis of crown ether analogs [5][6]. The disaccharide scaffold is much less pronounced [7]. During the past decade we have

• out that this methodology, which is used in the synthesis of more simple derivatives such as higher carbon sugars, was also applicable for the preparation of the sucrose dimer. Experimental General methods All reported NMR spectra were recorded with a Varian-Vnmrs-600 MHz spectrometer (at 600 and 150

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

• ., through molecular recognition of a preferred binding site [2][3][4][5], thereby ensuring the selectivity of a chemotherapeutic agent. Particularly common are side chains composed of deoxygenated sugars [6]. For example, the kigamicins are bacterial secondary metabolites isolated from Amicolatopsis sp. [7

• agent with particular activity against different forms of leukemia [13] (Figure 1). Desoxy-sugars are sometimes scarcely available from natural sources and therefore the chemical syntheses of the monosaccharides [6][14] and their assembly to oligosaccharides [15][16][17] has attracted constant attention

• sugar biosynthesis genes [5]. Comparatively few transition metal mediated or -catalyzed reactions have hitherto been used for the synthesis of 2,3,6-tridesoxy sugars such as amicetose. An example is the W-promoted cycloisomerization of lactaldehyde derived alkynols, which yields the glycal of amicetose

Molecular architecture with carbohydrate functionalized β-peptides adopting 3₁₄-helical conformation

• Nitin J. Pawar,
• Navdeep S. Sidhu,
• George M. Sheldrick,
• Dilip D. Dhavale and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2014, 10, 948–955, doi:10.3762/bjoc.10.93

• corresponding lectins. Taillefumier and coworkers link sugar units to β-peptide amino acid side chains by azide–alkyne cycloaddition [20]. Following the concept of highly organized presentation of sugar units on a β-peptide scaffold, we report on simultaneous incorporation of various sugars (glucose, galactose

• peptide scaffolds for the presentation of sugar epitopes has already some precedence. Complex saccharide structures are linked to α-peptides, protein fragments [24][25][26][27] and recently also to glycofoldamers [28]. Sugars are arranged on cyclopeptides [29][30][31][32][33], like Dumy and coworkers

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

• 1. A number of suitably functionalized monosaccharide intermediates 2, 3 [30], 4 [31], and 5 [32] were prepared from the reducing sugars by using literature reports. The application of a one-pot reaction sequence for the stereoselective glycosylation and the removal of the p-methoxybenzyl (PMB

Multigramme synthesis and asymmetric dihydroxylation of a 4-fluorobut-2E-enoate

• James A. B. Laurenson,
• John A. Parkinson,
• Jonathan M. Percy,
• Giuseppe Rinaudo and
• Ricard Roig

Beilstein J. Org. Chem. 2013, 9, 2660–2668, doi:10.3762/bjoc.9.301

• ][9][10]. The synthesis of fluorinated analogues of sugars can be approached in two strategically different ways. The most common, and often most efficient approach, identifies a sugar precursor, isolates the locus for fluorination (usually an hydroxy group) by protecting all the other functional

• -deoxy-6-fluoro sugars, the locus of reaction is not even a stereogenic centre. The synthesis of 6-fluoro-D-olivose (6) in 23% overall yield from optically pure D-glucose (1) by O’Hagan and Nieschalk (Scheme 1) provides an impressive example of the approach [12]. Isolation of the C-6 hydroxy group in 2

• /deprotection chemistry, and in some cases, the availability of the precursor sugar. Some less common sugars are expensive and available in limited quantities. The alternative approach involves de novo stereodivergent synthesis, which elaborates small fluorinated building blocks using the reactions of modern

The total synthesis of D-chalcose and its C-3 epimer

• Jun Sun,
• Song Fan,
• Zhan Wang,
• Guoning Zhang,
• Kai Bao and
• Weige Zhang

Beilstein J. Org. Chem. 2013, 9, 2620–2624, doi:10.3762/bjoc.9.296

• group via exposure to CSA/MeOH for 45 min at 0 °C; this process afforded alcohol 12 in good yield. The notable advantage of this strategy is its high degree of flexibility, rendering it applicable to the preparation of various C-3 analogues of chalcose and other related 4-deoxy sugars. Retrosynthesis of

Biosynthesis of rare hexoses using microorganisms and related enzymes

• Zijie Li,
• Yahui Gao,
• Hideki Nakanishi,
• Xiaodong Gao and
• Li Cai

Beilstein J. Org. Chem. 2013, 9, 2434–2445, doi:10.3762/bjoc.9.281

• of Mathematics and Science, University of South Carolina Salkehatchie, Walterboro, South Carolina, 29488, USA 10.3762/bjoc.9.281 Abstract Rare sugars, referred to as monosaccharides and their derivatives that rarely exist in nature, can be applied in many areas ranging from foodstuffs to

• pharmaceutical and nutrition industry, or as starting materials for various natural products and drug candidates. Unfortunately, an important factor restricting the utilization of rare sugars is their limited availability, resulting from limited synthetic methods. Nowadays, microbial and enzymatic

• -gulose, L-galactose, L-fucose, allitol, D-talitol, and L-sorbitol. New systems and robust catalysts resulting from advancements in genomics and bioengineering are also discussed. Keywords: biosynthesis; enzyme; hexose; microorganism; rare sugars; Introduction Rare sugars are referred to as

Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

• Felix Wojcik,
• Sinaida Lel,
• Alexander G. O’Brien,
• Peter H. Seeberger and
• Laura Hartmann

Beilstein J. Org. Chem. 2013, 9, 2395–2403, doi:10.3762/bjoc.9.276

• from an alphabet of building blocks, applying them for solid-phase synthesis and final cleavage from the resin, the desired multivalent structures can be obtained. Heteromultivalent glycooligomers presenting different sugars at different positions along the scaffold should be accessible by combining

• distance of sugar ligands as well as the sequence-defined introduction of different sugars are demonstrated by choosing different building block combinations during solid-phase synthesis. Results and Discussion For the preparation of the desired sugar building blocks double-bond presenting building block

• -analogue strategy is required where different functional groups are placed along a polymer chain that allow for orthogonal conjugation strategies introducing the different sugars sequentially [37][46]. Our approach simply relies on choosing from our differently glycosylated building blocks that are

Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties

• Catalin V. Maftei,
• Elena Fodor,
• Peter G. Jones,
• M. Heiko Franz,
• Gerhard Kelter,
• Heiner Fiebig and
• Ion Neda

Beilstein J. Org. Chem. 2013, 9, 2202–2215, doi:10.3762/bjoc.9.259

• transport in cells by using natural transporters such as amino acids, peptides or sugars. Moreover, it is desirable to reduce, or even remove completely, the secondary effects to minimize the toxicity and increase the selectivity. All derivatives were obtained with a high purity (at least 97% based on 1H

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• substitution pattern of the D-ring bares most of the functionalities, i.e., a secondary and a tertiary alcohol, the former of which is commonly glycosylated with 2,6-dideoxy sugars (Figure 1) [3]. These carbohydrates are of highest importance for the biological activity of anthracyclines and bind to the minor