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

• able to compare aminopyran 1 with aminopolyol 2 two divalent amides were synthesized from compound 16 using the same carboxylic acid dichlorides 7 and 8 as linkers affording the desired compounds 18 and 19 in excellent yields (Table 2, entries 1 and 2). Moreover, another divalent amide 20 with a longer

Synthesis and surface grafting of a β-cyclodextrin dimer facilitating cooperative inclusion of 2,6-ANS

• Lars W. Städe,
• Thorbjørn T. Nielsen,
• Laurent Duroux,
• Reinhard Wimmer,
• Kyoko Shimizu and
• Kim L. Larsen

Beilstein J. Org. Chem. 2015, 11, 514–523, doi:10.3762/bjoc.11.58

• demonstrated that the choice of linker is an important parameter in order to fully access both cavities [12][13]. Specifically, it was demonstrated that long and/or hydrophobic linkers may induce an inversion process, resulting in self-inclusion of the linker in one of the cavities, thereby limiting

C-5’-Triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides: Synthesis and biological evaluation

• Roberto Romeo,
• Caterina Carnovale,
• Salvatore V. Giofrè,
• Maria A. Chiacchio,
• Adriana Garozzo,
• Emanuele Amata,
• Giovanni Romeo and
• Ugo Chiacchio

Beilstein J. Org. Chem. 2015, 11, 328–334, doi:10.3762/bjoc.11.38

• can interact with intracellular targets to induce cytotoxicity [28][29][30][31][32]. Several functionalities have been inserted as linkers on the 2’-oxa-3’-aza-4’a-carbanucleoside skeleton in order to confer novel mechanisms of action for nucleoside mimics: in this context, the 1,2,3-triazole unit

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• phenanthridine moiety – many ethidium bromide-based dimers were prepared and reviewed in the last two decades of the 20th century, thus here will be presented results from 2000 on. Systematic variation of steric and/or electrostatic effects by means of type, number, length and flexibility of linkers connecting

• intercalator able to differentiate between A–U(T) and G–C base pairs by sign of opposite fluorimetric response. An introduction of the permanent positive charge by methylation of the heterocyclic nitrogen changed the binding mode of the conjugates with shorter linkers from minor groove binding to intercalation

• RNA dyes. Another large series of phenanthridinium-homodimers was constructed by linking two ethidium bromide subunits by peptide-like linkers of variable flexibility and rich in hydrogen-bonding possibilities within the DNA grooves (Figure 5). The resulting bis-intercalators (in comparison to the

Synthesis and characterization of a new photoinduced switchable β-cyclodextrin dimer

• Florian Hamon,
• Claire Blaszkiewicz,
• Marie Buchotte,
• Estelle Banaszak-Léonard,
• Hervé Bricout,
• Sébastien Tilloy,
• Eric Monflier,
• Christine Cézard,
• Laurent Bouteiller,
• Christophe Len and
• Florence Djedaini-Pilard

Beilstein J. Org. Chem. 2014, 10, 2874–2885, doi:10.3762/bjoc.10.304

• to the guest molecules [9][10]. These cyclodextrins linked by ester [11], thioether [12][13][14][15][16], urea [17][18][19], or triazole [20] moieties have been previously described. In addition, aromatic azobenzenes are excellent candidates as molecular switch linkers as they have two forms, namely

• cyclic polymers are aggregated into larger objects stabilized by hydrogen bonds between cyclodextrin moieties and by π-stacking interactions between azobenzene linkers. Finally, according to the computational data, the complexes of AZO-CDim 1 with ADAdim 4 are further stabilized by intramolecular

Synthesis of nanodiamond derivatives carrying amino functions and quantification by a modified Kaiser test

• Gerald Jarre,
• Steffen Heyer,
• Elisabeth Memmel,
• Thomas Meinhardt and
• Anke Krueger

Beilstein J. Org. Chem. 2014, 10, 2729–2737, doi:10.3762/bjoc.10.288

• with amino groups is typically not complete and the stability of amino groups directly bound to the diamond surface is limited as they are at least partially replaced by hydroxy groups under ambient conditions [4]. Therefore, in most cases linkers are used in order to establish stable bonding

• , the linkers are coupled to the diamond surface via heteroatoms. These sites are more easily cleaved compared to carbon–carbon single bonds, e.g., in a physiological environment or other aqueous conditions. It is hence of interest to develop methods that form stable bonds between the diamond surface

• ) BH3·THF, f) Δ, 1,2-dichlorobenzene, g) MCPBA, h) NH3, i) BH3·THF, j) APTMS, k) 4-aminobenzyl(N-Boc)amine, isopentyl nitrite, l) TFA. Surface loading of nanodiamond-carrying amino groups on different linkers using three independent quantification methods. Supporting Information Supporting Information

Synthesis and characterization of a hyper-branched water-soluble β-cyclodextrin polymer

• Francesco Trotta,
• Fabrizio Caldera,
• Roberta Cavalli,
• Andrea Mele,
• Carlo Punta,
• Lucio Melone,
• Franca Castiglione,
• Barbara Rossi,
• Monica Ferro,
• Vincenza Crupi,
• Domenico Majolino,
• Valentina Venuti and
• Dominique Scalarone

Beilstein J. Org. Chem. 2014, 10, 2586–2593, doi:10.3762/bjoc.10.271

• structural aspects and functional properties, and in particular pyromellitic nanosponges were found to present a critical cross-linking value [17]. In other words, the maximum number of cross-linkers per monomer was proved to be around 6 (i.e., 6 mol of pyromellitic dianhydride for each mol of β-CD). If the

Towards the sequence-specific multivalent molecular recognition of cyclodextrin oligomers

• Michael Kurlemann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 2428–2440, doi:10.3762/bjoc.10.253

• for the interaction with α-CD, the EM cannot be increased that easy. Here the linkers of the guest and the host moieties have a crucial influence on the structure of the divalent molecules and the host–guest complexes before the intramolecular complexation [1]. Changes in the linkers’ structures can

Reversibly locked thionucleobase pairs in DNA to study base flipping enzymes

• Christine Beuck and
• Elmar Weinhold

Beilstein J. Org. Chem. 2014, 10, 2293–2306, doi:10.3762/bjoc.10.239

• , long linkers that might interfere with protein binding are typically employed. The Verdine group has developed a cross-linking approach based on the easy postsynthetic introduction of cystamine or longer amino-alkylthiol linkers into ODN using a convertible nucleoside approach [39][40][41][42][43][44

• its neighboring base pairs. In contrast, the ideal geometry of saturated linkers will demand non-planar torsion angles. Coleman et al. [44] investigated this topic by performing molecular dynamic simulations for a disulfide cross-linked I6S/U4S base pair in B-DNA and showed that the compromise between

Molecular recognition of AT-DNA sequences by the induced CD pattern of dibenzotetraaza[14]annulene (DBTAA)–adenine derivatives

• Marijana Radić Stojković,
• Marko Škugor,
• Łukasz Dudek,
• Jarosław Grolik,
• Julita Eilmes and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2175–2185, doi:10.3762/bjoc.10.225

• stacked dimers within the DNA minor groove similar to the crystal structure of close analogue (Figure 4, right). Conversely, the AP5 and AP6 aliphatic linkers are long enough to allow self-folding and easy intramolecular π–π stacking of adenine with DBTAA (Figure 4, upper right). During the binding event

Macrocyclic bis(ureas) as ligands for anion complexation

• Claudia Kretschmer,
• Gertrud Dittmann and
• Johannes Beck

Beilstein J. Org. Chem. 2014, 10, 1834–1839, doi:10.3762/bjoc.10.193

• ring with two ethynylene groups as linkers and 2 the larger ring with two butadiynylene groups. On thermal treatment to 130 °C molecule 1 splits up into two dihydroindoloquinolinone (3) molecules. Both compounds 1 and 2 form adducts with polar molecules such as dimethyl sulfoxide (DMSO) and

• planar ligand, as was shown by indole-based macrocycles [9]. This ligand system represents a stiff ring of two bis(indole) units connected via two ethynylene groups as linkers. As proven by a crystal structure determination, a chloride ion fits into the cavity bound via four N−H∙∙∙Cl bonds and strong

• butadiynylene groups as spacers turned out as a suitable receptor for small anions with high binding constants. The molecule is flexible. In the complex with a bromide ion embedded in the ring cavity, the cyclic ligand is strongly tilted. The smaller cycle with ethynylene groups as linkers is a much weaker

Influence of perylenediimide–pyrene supramolecular interactions on the stability of DNA-based hybrids: Importance of electrostatic complementarity

• Christian B. Winiger,
• Simon M. Langenegger,
• Oleg Khorev and
• Robert Häner

Beilstein J. Org. Chem. 2014, 10, 1589–1595, doi:10.3762/bjoc.10.164

• (Table 1, hybrids 1*2 and 7*6) than hybrids containing both types of aromatic compounds. Although the actual stability of such duplexes strongly depends on several parameters like, e.g., the geometry of the building blocks and the flexibility of the linkers, a general trend can be deduced from the

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

• moieties and an aromatic central core but the introduction of distinct functionalized linkers may change the overall hydrophobic/hydrophilic balances of the structures. As such, they could engage supplementary intramolecular hydrogen bonding or hydrophobic interactions that could mediate their three

• ranging from 1.51 to 1.33 × 10−10 m2s−1 for protons in the core or the periphery. Interestingly, calculation of the extended conformation (MM2, Chem3D) of the linkers in 12, 17, and 21 showed lengths of 14.8, 17.1, and 21.8 Å, respectively. Conclusion The syntheses of three related families of

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

• protonable amines into neutral amide or carbamate linkers. Even though PEGylation of chitosan via the amino group is the most commonly used method a number of examples of polysaccharide derivatisation on the hydroxy groups have been reported. Chitosan-O-poly(ethylene glycol) graft copolymers were synthesized

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• ) group [43]). For a precise overview, the review of Isidro-Llobet 2009 and detailed manuals of major companies are recommended [44][45][46]. Optimal resins and linkers for peptide synthesis: The solid phase has to meet a number of requirements to be suitable for peptide synthesis. It has to be insoluble

• . recently published a collection of commonly used resins, together with their individual swelling and loading (is defined by the equivalents of amino acid in mmol/g, which can be attached to the resin) properties [50]. With respect to PEG-functionalized linkers, peptide synthesis yields can be improved by

• -terminus can be modified as hydrazide, alcohol, aldehyde, thioester and many more [22][50]. Furthermore, there are linkers that enable the synthesis of partially and fully protected peptides such as the 2-chlorotrityl resin [51] or the Sieber amide resin [52]. Consequently, the choice of resin and linker

N-Alkylated dinitrones from isosorbide as cross-linkers for unsaturated bio-based polyesters

• Oliver Goerz and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 902–909, doi:10.3762/bjoc.10.88

• ) were used as model systems and reacted with dimethyl itaconate to further characterize the 1,3-dipolaric cycloaddition. Keywords: bio-based polyesters; cross-linkers; dinitrones; 1,3-dipolar cycloaddition; isosorbide; Introduction Nitrones represent a class of compounds with a versatile use as

• synthesis of polymers bearing nitrones as photosensitive material [7][8] was also described. We focused on the preparation of polynitrones as efficient cross-linkers for unsaturated polyesters based on fumaric und maleic acid [9]. In the light of the growing interest in polymers from renewable resources the

• synthesis of bio-based nitrones as novel cross-linkers for unsaturated bio-polyesters [10] offers an interesting access to biocompatible materials. This paper presents the synthesis of bio-based N-alkylated dinitrones based on isosorbide and the subsequent use of these dinitrones as cross-linkers in a 1,3

Staudinger ligation towards cyclodextrin dimers in aqueous/organic media. Synthesis, conformations and guest-encapsulation ability

• Malamatenia D. Manouilidou,
• Yannis G. Lazarou,
• Irene M. Mavridis and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 774–783, doi:10.3762/bjoc.10.73

• couplings [16][23], the classical formation of ester [12][17], amide [25][26] or imide [27] bonds between CDs or amino CDs and acid- or anhydride-linkers, and finally urea/thiourea bonds [28][29]. However, the obvious advantages of the Staudinger ligation (high reaction rates, absence of a catalyst, aqueous

•  1, Figure S1). Compound 3 showed a single methoxy group in the 1H NMR spectrum (3.57 ppm) and a single carbonyl signal in the 13C NMR spectrum (166.8 ppm), reflecting the compound’s high molecular symmetry. Both linkers were stored under argon at −20 °C to minimize oxidation, although best results

• studied the mechanism of the Staudinger ligation of arylphosphine ester linkers such as 2 with various alkyl azide substrates [7]. They have shown that the ligation is a second order process: polar protic solvents and electron-donating substituents on the aryphosphine accelerate the reaction, while the

Preparation of new alkyne-modified ansamitocins by mutasynthesis

• Kirsten Harmrolfs,
• Lena Mancuso,
• Binia Drung,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2014, 10, 535–543, doi:10.3762/bjoc.10.49

• that a release mechanism of the cytotoxin is part of the molecular architecture of the conjugate [31]. Disulfide linkers have shown to be well suited when utilizing the reducing power between extra- and intracellular milieus which results in cleavage and liberation of the drug. Mitomycin conjugates [32

Studies toward bivalent κ opioids derived from salvinorin A: heteromethylation of the furan ring reduces affinity

• Thomas A. Munro,
• Wei Xu,
• Douglas M. Ho,
• Lee-Yuan Liu-Chen and
• Bruce M. Cohen

Beilstein J. Org. Chem. 2013, 9, 2916–2924, doi:10.3762/bjoc.9.328

• ligands with a furanylmethyl substituent (Figure 3), we decided to use a short linker. As an alternative approach, bivalent ligands with much longer linkers can bind simultaneously to both protomers in a receptor dimer, allowing selective targeting of specific receptor oligomers [21]. We also sought to

• provide a suitable attachment point for such linkers based on our previous studies of C-2 alkoxymethyl ethers [22][23], which have higher tolerance to alkyl chain extension [24] than other derivatives of 1 [1]. Results Synthesis Initial attempts to form the 16-dimethylaminomethyl derivative 2 by treatment

• is thus not a promising attachment point. At the opposite extreme, the C-2 alkoxymethyl ether series is highly tolerant to alkyl chain extension. Compound 6 and the synthetic route used may prove useful for the attachment of very long linkers, as used with other scaffolds to bridge receptor dimers

Synthesis of nucleotide–amino acid conjugates designed for photo-CIDNP experiments by a phosphotriester approach

• Tatyana V. Abramova,
• Olga B. Morozova,
• Vladimir N. Silnikov and
• Alexandra V. Yurkovskaya

Beilstein J. Org. Chem. 2013, 9, 2898–2909, doi:10.3762/bjoc.9.326

• conjugates consisting of amino acid, nucleotide, and dye residues including linkers of different lengths (Figure 1). Target compounds 1–8 have been synthesized by the phosphotriester block liquid phase synthesis (LPS). Results and Discussion Design of model compounds Our previous studies revealed a great

Gold(I)-catalyzed hydroarylation reaction of aryl (3-iodoprop-2-yn-1-yl) ethers: synthesis of 3-iodo-2H-chromene derivatives

• Pablo Morán-Poladura,
• Eduardo Rubio and
• José M. González

Beilstein J. Org. Chem. 2013, 9, 2120–2128, doi:10.3762/bjoc.9.249

• , two facts are of mechanistic significance. First, the 2:3 ratio for a given R substituent (Scheme 4A, R = 4-Cl) can be compared for the two linkers. For the nitrogen-containing tether (X = NTs, Scheme 4A), almost exclusive formation of 2 was noticed (reaction in 1,2-dichloroethane, at rt for 24 h, [43

Polymeric redox-responsive delivery systems bearing ammonium salts cross-linked via disulfides

• Christian Dollendorf,
• Martin Hetzer and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 1652–1662, doi:10.3762/bjoc.9.189

• or CL 2, or both cross-linkers (Scheme 2). Rheological measurements of cross-linked polymer discs To investigate the rheological characteristics of cross-linked polycationic hydrogels, polymer discs of poly(DEAAm-co-DMAEMA, 1:1) containing between 1.0 and 5.0 mol % of either CL 1 (samples 4), or CL 2

• (samples 5), or both cross-linkers (samples 6) were synthesized. The samples were immersed in distilled water until the equilibrium state of swelling was reached. The swollen samples were then used for oscillatory measurements using the serrated plate–plate geometry. As expected, the storage modulus G

• the enhanced affinity for interactions with water molecules leads to a better enclosure of water and therefore a higher swelling degree. Sample 6, which contains both cross-linkers, shows the lowest values for Q. This can be attributed to its overall higher content of cross-linker, compared to samples

Molecular assembly of amino acid interlinked, topologically symmetric, π-complementary donor–acceptor–donor triads

• M. B. Avinash,
• K. V. Sandeepa and
• T. Govindaraju

Beilstein J. Org. Chem. 2013, 9, 1565–1571, doi:10.3762/bjoc.9.178

• acids as linkers is due to their compactness, variable side chain functionality and sequence-specific self-assembling properties and the desire to exploit their inherent chiral information for helical assembly of electro-active molecular materials [35][36][37][38][39][40][41][42][43][44][45][46][47][48

Synthesis and evaluation of cell-permeable biotinylated PU-H71 derivatives as tumor Hsp90 probes

• Tony Taldone,
• Anna Rodina,
• Erica M. DaGama Gomes,
• Matthew Riolo,
• Hardik J. Patel,
• Raul Alonso-Sabadell,
• Danuta Zatorska,
• Maulik R. Patel,
• Sarah Kishinevsky and
• Gabriela Chiosis

Beilstein J. Org. Chem. 2013, 9, 544–556, doi:10.3762/bjoc.9.60

• compounds that demonstrate such combined properties (Figure 1). As such we have prepared a number of biotinylated analogues, derived from 1a and 1b, containing linkers of various lengths (1 to 17 atoms) and hydrophobicities (polyethylene-, amide- and/or alkyl-containing). In addition, an amine-linked biotin

• essential that the linker be of sufficient length to enable the concomitant binding to Hsp90 and streptavidin, it is also important that it is not exceedingly long for two reasons. First, the possibility and extent of nonspecific binding increases with longer linkers. Second, longer linkers result in a

• ), despite the fact that both 1a and 1b bound Hsp90 with similar affinity (24.5 versus 26 nM for 1a and 1b, respectively). This is likely a result of increased steric crowding of the bulky isopropyl group in analogues of 1a. Second, in terms of the linkers, the carbon series appeared to have a somewhat

Spin state switching in iron coordination compounds

• Philipp Gütlich,
• Ana B. Gaspar and
• Yann Garcia

Beilstein J. Org. Chem. 2013, 9, 342–391, doi:10.3762/bjoc.9.39