Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• from acetate (bold) and L-isoleucine (red) as deduced from labeling experiments. Labels introduced into the carbohydrates and methyl groups are omitted. Proposed biosynthetic assembly of clostrubin A (12). Bold bonds show intact acetate units. Proposed biosynthesis of aspirochlorine (20) via 18 and 19

Synthesis of D-fructose-derived spirocyclic 2-substituted-2-oxazoline ribosides

• Madhuri Vangala and
• Ganesh P. Shinde

Beilstein J. Org. Chem. 2015, 11, 2289–2296, doi:10.3762/bjoc.11.249

• spiro [42] 2-oxazolines [43] are limited, to the best of our knowledge. With our interest in the area of glycopeptides [44] and carbohydrates [45], and owing to the importance of ribosides in general and spiroribofuranoses [46] in particular for drug discovery, in this paper, we report the synthesis of

Towards inhibitors of glycosyltransferases: A novel approach to the synthesis of 3-acetamido-3-deoxy-D-psicofuranose derivatives

• Maroš Bella,
• Miroslav Koóš and
• Chun-Hung Lin

Beilstein J. Org. Chem. 2015, 11, 1547–1552, doi:10.3762/bjoc.11.170

• mimetics. Despite all the effort and the numerous GTs inhibitors identified, only a few achieved significant activity. On the basis of the previous investigations, a new class of GTs inhibitors imitating carbohydrates has been revealed [17]. These structurally modified carbohydrates are designed to

Cross-metathesis reaction of α- and β-vinyl C-glycosides with alkenes

• Ivan Šnajdr,
• Kamil Parkan,
• Filip Hessler and
• Martin Kotora

Beilstein J. Org. Chem. 2015, 11, 1392–1397, doi:10.3762/bjoc.11.150

• ; catalysis; carbohydrates; cross-metathesis; ruthenium; Introduction Natural and unnatural C-substituted glycosides are important compounds with a plethora of attractive biological properties and they often have been used as artificial DNA components [1]. Among various synthetic procedures providing C

Synthesis and evaluation of the biostability and cell compatibility of novel conjugates of nucleobase, peptidic epitope, and saccharide

• Dan Yuan,
• Xuewen Du,
• Junfeng Shi,
• Ning Zhou,
• Abdulgader Ahmed Baoum,
• Khalid Omar Al Footy,
• Khadija Omar Badahdah and
• Bing Xu

Beilstein J. Org. Chem. 2015, 11, 1352–1359, doi:10.3762/bjoc.11.145

• they constitute three key types of biomacromolecules–proteins, nucleic acids, and carbohydrates. Inspired by this molecular foundation resulted from evolution, we are developing biomaterials that consist of the covalent conjugates of these three classes of the basic building blocks of life. For example

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• 139 by using the Wurtz coupling as a key step (Scheme 20). Metathesis Alkyne metathesis reaction: In 2010, Murphy and Jarikote [139] have developed a useful protocol for assembling non-natural macrocyclic compounds containing carbohydrates. Compound 140 was prepared in several steps and was further

Terminal lipophilization of a unique DNA dodecamer by various nucleolipid headgroups: Their incorporation into artificial lipid bilayers and hydrodynamic properties

• Emma Werz and
• Helmut Rosemeyer

Beilstein J. Org. Chem. 2015, 11, 913–929, doi:10.3762/bjoc.11.103

• lipo-oligonucleotides. Keywords: lipid bilayer; lipo-oligonucleotides; nucleic acids; nucleolipids; Introduction For proper cell function, the biosynthetic lipophilization of proteins and carbohydrates, such as palmitoylation and farnesylation, is of decisive importance [1]. The same seems to be true

Glycodendrimers: tools to explore multivalent galectin-1 interactions

• Jonathan M. Cousin and
• Mary J. Cloninger

Beilstein J. Org. Chem. 2015, 11, 739–747, doi:10.3762/bjoc.11.84

• located on apposing faces of the dimer (Figure 1). Although individual binding interactions with carbohydrates are weak [8], ligands for galectin-1 typically possess an array of carbohydrates to enhance the binding affinity [1][9][10]. Galectin-1 binding to carbohydrates cross-links adjacent

Probing multivalency in ligand–receptor-mediated adhesion of soft, biomimetic interfaces

• Stephan Schmidt,
• Hanqing Wang,
• Daniel Pussak,
• Simone Mosca and
• Laura Hartmann

Beilstein J. Org. Chem. 2015, 11, 720–729, doi:10.3762/bjoc.11.82

• protein receptors are formed to control cell–cell recognition, cell adhesion and related processes. The aim of this work is to shed light on the principles of complex formation between surface anchored carbohydrates and receptor surfaces by measuring the specific adhesion between surface bound mannose on

• carbohydrates of the glycocalyx, a glycan coating enveloping prokaryotic or eukaryotic cells. By specific binding to cell receptors, the carbohydrate units of the glycocalyx control important processes such as cell adhesion, communication and inflammatory response [1]. For this reason great effort is set forth

• ligands are typically oligomers consisting of multiple subunits of varying complexity. When binding to receptors this leads to a receptor clustering or so-called glycocluster effect. However, multivalency even goes further: For example when cells form contact layers of surface anchored carbohydrates the

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• is a longstanding interest in tools to manipulate these interactions for structure–function studies and as potential therapeutics [8][9]. The demonstration that the high avidity of oligomeric interactions with cell surface carbohydrates can be outcompeted with a synthetic scaffold that recapitulates

• diverse glycans could be iteratively introduced on amino acid linkers. Inspired by Shoda’s activation [40] which provides facile access to complex glycosyl azides from native carbohydrates, we subsequently applied reiterative CuAAC conjugation of glycans on propargyl glycine residues within a peptide [41

Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors

• Joana Salta,
• Jens Dernedde and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2015, 11, 638–646, doi:10.3762/bjoc.11.72

• since in the literature similar conditions were found for the synthesis of multivalent acetyl-protected carbohydrates [29]. As possible explanation we assume that the formation of product 6 is sterically too hindered due to the bulkiness of the TBS-protecting groups of 3 and the short distance between

Synthesis of 1,2-cis-2-C-branched aryl-C-glucosides via desulfurization of carbohydrate based hemithioacetals

• Henok H. Kinfe,
• Fanuel M. Mebrahtu,
• Mandlenkosi M. Manana,
• Kagiso Madumo and
• Mokela S. Sokamisa

Beilstein J. Org. Chem. 2015, 11, 583–588, doi:10.3762/bjoc.11.64

• Henok H. Kinfe Fanuel M. Mebrahtu Mandlenkosi M. Manana Kagiso Madumo Mokela S. Sokamisa Department of Chemistry, University of Johannesburg, PO Box 524, Auckland Park 2006, South Africa 10.3762/bjoc.11.64 Abstract 1-C and 2-C-branched carbohydrates are present as substructures in a number of

• stereospecific preparation of 2,3-unsaturated-aryl-C-glycosides (Ferrier products). Keywords: aryl-C-glucoside; desulfurization; Ferrier product; hemithioacetal; Introduction 1-C (C-glycosides) and 2-C-branched carbohydrates are important carbohydrate analogues which have found wide application in

• to C-glycosides are 2-C-branched carbohydrates which are employed as bioisosters of the natural 2-acetamido glycoside derivatives. Gammon et al. prepared a series of 2-C-branched carbohydrates as potential inhibitors of enzymes implicated in the biosynthesis of mycothiol, Mycobacterium tuberculosis’s

Properties of cationic monosubstituted tetraalkylammonium cyclodextrin derivatives – their stability, complexation ability in solution or when deposited on solid anionic surface

• Martin Popr,
• Sergey K. Filippov,
• Nikolai Matushkin,
• Juraj Dian and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2015, 11, 192–199, doi:10.3762/bjoc.11.20

• , yet robust and a straightforward process as well. Keywords: cyclodextrins; inclusion properties; solid surface; tetraalkylammonium derivatives; thermal stability; Introduction Cyclodextrins (CDs) are a very interesting group of natural macrocyclic carbohydrates, which were first described by

Synthesis and biological evaluation of a novel MUC1 glycopeptide conjugate vaccine candidate comprising a 4’-deoxy-4’-fluoro-Thomsen–Friedenreich epitope

• Manuel Johannes,
• Maximilian Reindl,
• Bastian Gerlitzki,
• Edgar Schmitt and
• Anja Hoffmann-Röder

Beilstein J. Org. Chem. 2015, 11, 155–161, doi:10.3762/bjoc.11.15

• selective IgG antibodies that are cross-reactive with native MUC1 epitopes on MCF-7 human cancer cells. Keywords: cancer immunotherapy; fluorinated carbohydrates; glycoconjugates; MUC1; TACA; Introduction Since cancer has advanced to one of the leading causes of death in economical developed countries

Articulated rods – a novel class of molecular rods based on oligospiroketals (OSK)

• Pablo Wessig,
• Roswitha Merkel and
• Peter Müller

Beilstein J. Org. Chem. 2015, 11, 74–84, doi:10.3762/bjoc.11.11

• relatively rigid molecular and supramolecular systems. These systems mainly consist of peptides and proteins (e.g., scleroproteins, globular proteins, and membrane proteins), lipids (e.g., biological membranes), carbohydrates (e.g., cellulose) and nucleic acids (DNA, RNA). The impressive performance of the

Release of β-galactosidase from poloxamine/α-cyclodextrin hydrogels

• César A. Estévez,
• José Ramón Isasi,
• Eneko Larrañeta and
• Itziar Vélaz

Beilstein J. Org. Chem. 2014, 10, 3127–3135, doi:10.3762/bjoc.10.330

• : controlled release; cyclodextrins; lactase; polypseudorotaxane; supramolecular gel; Introduction In the Western diet, carbohydrates contribute about 50% of calories, distributed in the following ratio: starch (50%), sucrose (30%), lactose (6%), maltose (1–2%), and others (12%: trehalose, glucose, fructose

Synthesis and characterization of pH responsive D-glucosamine based molecular gelators

• Navneet Goyal,
• Hari P. R. Mangunuru,
• Bargav Parikh,
• Sonu Shrestha and
• Guijun Wang

Beilstein J. Org. Chem. 2014, 10, 3111–3121, doi:10.3762/bjoc.10.328

• be effective LMWGs, including derivatives from amino acids, carbohydrates, and cholesterols derivatives [8][9][10][11][12][13][14][15][16]. The reversible organogels and hydrogels have been explored for many applications including drug delivery, protein binding and separation, tissue engineering, and

Preparation and evaluation of cyclodextrin polypseudorotaxane with PEGylated liposome as a sustained release drug carrier

• Kayoko Hayashida,
• Taishi Higashi,
• Daichi Kono,
• Keiichi Motoyama,
• Koki Wada and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2014, 10, 2756–2764, doi:10.3762/bjoc.10.292

• rapid removal from the systemic circulation by the reticuloendothelial system (RES). To produce long-circulating LPs, hydrophilic polymers, carbohydrates, peptides and proteins have been used to modify the surface of LPs [29]. Additionally, the targeting efficiency of LPs has been improved by appending

Synthesis of aromatic glycoconjugates. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger and
• Thomas Ziegler

Beilstein J. Org. Chem. 2014, 10, 2453–2460, doi:10.3762/bjoc.10.256

• acids; aniline; carbohydrates; glycoconjugates; glycopeptides; Introduction Glycans or other complex oligosaccharide structures, present on the surface of every prokaryotic and eukaryotic cell, are important for a large number of biological recognition processes like, for example, intercellular

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

• the native polymer and conjugated to the same protein. This finding suggests that oligomers longer than three repeating units are possibly needed to mimic the activity of the native polysaccharide. Keywords: carbohydrates; glycoconjugates; immunology; multivalent glycosystems Neisseria meningitidis

• activated oligomers. To increase the yield of this step, compounds 11–13 were recovered from the dimethylsulfoxide–ethyl acetate mixture by evaporation of ethyl acetate and addition of fresh ethyl acetate at 0 °C. The newly precipitated activated carbohydrates were freeze-dried and coupled to the protein

• well-defined carbohydrates for the development of a glycoconjugate vaccine. While, at the present dose and carbohydrate loading, conjugates of the synthetic MenX PS monomer and dimer with CRM197 were poorly antigenic, the conjugated trimer resulted in the minimal structure eliciting antibodies that can

Multivalent glycosystems for nanoscience

• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2014, 10, 2345–2347, doi:10.3762/bjoc.10.244

• Thisbe K. Lindhorst Otto Diels Institute of Organic Chemistry, Christiana Albertina University of Kiel, Otto-Hahn-Platz 3/4, 24098 Kiel, Germany 10.3762/bjoc.10.244 Keywords: multivalent glycosystems; Carbohydrates constitute the most abundant class of biomolecules on Earth. They are “global

• surface. Hence, carbohydrates are like Alice’s Wonderland—they can assume any role. They can be big or small, sweet or sour, silent or explicit, crucial or, less often, irrelevant. What we do understand, however, is that carbohydrates are essential to life, both in a state of health and in the case of

• disease. Consequently, the glycosciences have gained great respect in chemistry and biology. It is now generally considered important to be able to synthesize carbohydrates and glycoconjugates, to purify and analyze their structures, and to advance our understanding of the biology of carbohydrates in

Specific DNA duplex formation at an artificial lipid bilayer: fluorescence microscopy after Sybr Green I staining

• Emma Werz and
• Helmut Rosemeyer

Beilstein J. Org. Chem. 2014, 10, 2307–2321, doi:10.3762/bjoc.10.240

• -biosynthetic lipophilization of various biomolecules such as of proteins and carbohydrates is of decisive importance for the correct function of the cell [1]. With the recent discovery of geranylated tRNAs in bacteria [2] the interest in so-called lipo-oligonucleotides (LONs) has grown tremendously [3][4]. The

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

• higher fluorescence staining of cell-surface glycoconjugates, the glucosamine derivative gave higher labeling efficiency with protein preparations containing also intracellular proteins. Keywords: bioorthogonal chemistry; carbohydrates; cyclopropenes; inverse-electron-demand Diels-Alder reactions

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

• azide reduction followed by final deacetylation using methanolic sodium methoxide furnishes the title compounds. Keywords: allylation; carbohydrates; epoxidation; indium; multivalent glycosystems; organocatalysis; Introduction The indium-mediated allylation of carbonyl compounds has proven to be a

• valuable tool for carbon chain elongation [1][2][3] in order to access rare, biologically active carbohydrates [4][5][6][7][8]. Herein we report the extension of this method towards the field of higher aminosugars by additionally applying a stereoselective epoxidation–azide opening strategy. The resulting

• allowing for an evaluation of structure–activity relationships. Results and Discussion We started our reaction sequence with an indium-mediated allylation of unprotected carbohydrates using D-arabinose (1a), D-galactose (1b) and D-glucose (1c) as starting materials. The Barbier-type chain elongation

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

• carbohydrates. In the context of our studies on the synthesis of sugar amino acids structurally related to iminosugar mannojirimycin (a strong inhibitor of α-mannosidase), we have recently prepared, by applying the Grignard reaction, several branched sugar carbinols as intermediates for subsequent oxidation to

• ) groups, respectively. Finally, the o-tolyl structure and benzyl structure of the moieties at C-5 atom of ketone 8 (Figure 1) and ketone 9 (Figure 2), respectively, (the numbering of the atoms is in accordance with the numbering recommended by the IUPAC Nomenclature of Carbohydrates [23]) was