Organic & Biomolecular Chemistry (Org Biomol Chem)

Publications in this journal

• Article: Synthesis of a selective inhibitor of a fucose binding bacterial lectin from Burkholderia ambifaria.

  Barbara Richichi, Anne Imberty, Emilie Gillon, Rosa Bosco, Ieva Sutkeviciute, Franck Fieschi, Cristina Nativi
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  ABSTRACT: Burkholderia ambifaria is a bacterium member of the Burkholderia cepacia complex (BCC), a closely related group of Gram-negative bacteria responsible for "cepacia syndrome" in immunocompromised patients. B. ambifaria produces BambL, a fucose-binding lectin that displays fine specificity to human fucosylated epitopes. Here, we report the first example of a synthetic ligand able to selectively bind, in the micromolar range, the pathogen-lectin BambL. The synthetic routes for the preparation of the α conformationally constrained fucoside are described, focusing on a totally diastereoselective inverse electron demand [4 + 2] Diels-Alder reaction. Isothermal titration calorimetry (ITC) demonstrated that this compound binds to the pathogen-associated lectin BambL with an affinity comparable to that of natural fucose-containing oligosaccharides. No binding was observed by LecB, a fucose-binding lectin from Pseudomonas aeruginosa, and the differences in affinity between the two lectins could be rationalized by modeling. Furthermore, SPR analyses showed that this fucomimetic does not bind to the human fucose-binding lectin DC-SIGN, thus supporting the selective binding profile towards B. ambifaria lectin.
  Organic & Biomolecular Chemistry 05/2013;
• Article: Trace amount Cu (ppm)-catalyzed intramolecular cyclization of 2-(gem-dibromovinyl)phenols(thiophenols) to 2-bromobenzofurans(thiophenes).

  Yong Ji, Pinhua Li, Xiuli Zhang, Lei Wang
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  ABSTRACT: An intramolecular cyclization of 2-(gem-dibromovinyl)phenols(thiophenols) to give 2-bromobenzofurans(thiophenes) in the presence of a trace amount of Cu (0.0064 mol%, 25 ppm) has been developed. The reaction provides the desired products in excellent yields under fluoride-free and mild reaction conditions and with a TON (turnover number) of up to 1.5 × 10(4).
  Organic & Biomolecular Chemistry 05/2013;
• Article: In-peptide synthesis of di-oxazolidinone and dehydroamino acid-oxazolidinone motifs as β-turn inducers.

  Rossella De Marco, Arianna Greco, Sebastiano Rupiani, Alessandra Tolomelli, Claudia Tomasini, Silvia Pieraccini, Luca Gentilucci
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  ABSTRACT: Small and easy-to-do mimetics of β-turns are of great interest to interfere with protein-protein recognition events mediated by β-turn recognition motifs. We propose a straightforward procedure for constraining the conformation of tetrapeptides lacking a pre-formed scaffold. According to the stereochemistry array, N-Ts tetrapeptides including Thr or PhSer (phenylserine) at the positions 2 or 3 gave rise in a single step to the sequences Oxd(2)-Oxd(3) or ΔAbu(2)-Oxd(3) (Oxd, oxazolidin-2-one; ΔAbu, 2,3-dehydro-2-aminobutyric). These pseudo-Pro residues displayed highly constrained ϕ, ψ, and χ dihedral angles, and induced clear β-turns or inverse turns of type I or II, as determined by extensive spectroscopic and computational analyses.
  Organic & Biomolecular Chemistry 05/2013;
• Article: A transition metal-free tandem process to pyridazinopyrido[3,2-f][1,4]thiazepine-diones via Smiles rearrangement.

  Xiaoyi Niu, Bingchuan Yang, Yanqiu Li, Shuai Fang, Zixiao Huang, Caixia Xie, Chen Ma
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  ABSTRACT: A transition metal-free methodology for the synthesis of pyridazinopyrido[3,2-f][1,4]thiazepine-diones was studied. The construction of this tricyclic system went through a one-pot coupling/Smiles rearrangement/cyclization process. The high yields of pure products were obtained through simple recrystallization.
  Organic & Biomolecular Chemistry 05/2013;
• Article: Biocompatible, multifunctional, and well-defined OEG-based dendritic platforms for biomedical applications.

  Lorena Simón-Gracia, Daniel Pulido, Chantal Sevrin, Christian Grandfils, Fernando Albericio, Miriam Royo
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  ABSTRACT: Given the growing importance of drug and gene delivery systems, imaging agents, biosensors, and theranostics, there is a need to develop new multifunctional and biocompatible platforms. Here we synthesized and fully characterized a family of novel multifunctional and completely monodisperse dendritic platforms. Our synthetic methodology, based on compatible protecting groups and the attachment of monodisperse triethylene glycol units, allows the control of the generation and differentiation of terminal groups, thus giving rise to multifunctional and perfectly-defined products. A family of dendrons was synthesized and four distinct dendritic structures were chosen from the family in order to determine the effect of the generation and surface groups on their biocompatibility. The stability in serum, cytotoxicity, and hemocompatibility of these products were studied. Our results indicate that these non-toxic, hemocompatible, non-immunogenic, stable and versatile scaffolds may be very interesting candidates for biomedical applications.
  Organic & Biomolecular Chemistry 05/2013;
• Article: Dibenzotetraaza[14]annulene-adenine conjugate recognizes complementary poly dT among ss-DNA/ss-RNA sequences.

  Marijana Radić Stojković, Marko Skugor, Sanja Tomić, Marina Grabar, Vilko Smrečki, Lukasz Dudek, Jarosław Grolik, Julita Eilmes, Ivo Piantanida
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  ABSTRACT: Among three novel DBTAA derivatives only the DBTAA-propyl-adenine conjugate showed recognition of the consecutive oligo dT sequence by increased affinity and specific induced chirooptical response in comparison to other single stranded RNA and DNA; whereby of particular importance is the up until now unique efficient differentiation between dT and rU. At variance, its close analogue DBTAA-hexyl-adenine did not reveal any selectivity between ss-DNA/RNA pointing out the important role of steric factors (linker length); moreover non-selectivity of the reference compound (, lacking adenine) stressed the importance of adenine interactions in the selectivity.
  Organic & Biomolecular Chemistry 05/2013;
• Article: Synthesis and pharmacological characterization of new tetrahydrofuran based compounds as conformationally constrained histamine receptor ligands.

  Julian Bodensteiner, Paul Baumeister, Roland Geyer, Armin Buschauer, Oliver Reiser
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  ABSTRACT: A series of tetrahydrofuran based compounds with a bicyclic core that provides conformational restriction were synthesized and investigated by radioligand displacement studies and functional [(35)S]GTPγS binding assays at the human histamine receptor (hHR) subtypes. The amines and ((1S,3R,5S,6R)- and ((1S,3S,5S,6R)-3-(1H-imidazol-5-yl)-2-oxabicyclo[3.1.0]hexan-6-yl)methanamine), exhibited submicromolar Ki values at the hH3R with 10-fold higher affinities than their corresponding (6S)-epimers and 25- and >34-fold selectivity over the hH4R, respectively. Both compounds act as neutral antagonists at the hH3R with KB values of 181 and 32 nM, respectively. The cyanoguanidines of the imidazole series and the oxazole analogues turned out to be inactive at all hHR subtypes.
  Organic & Biomolecular Chemistry 05/2013;
• Article: Synthesis and antiproliferative activity of selenoindirubins and selenoindirubin-N-glycosides.

  Friedrich Erben, Dennis Kleeblatt, Marcel Sonneck, Martin Hein, Holger Feist, Thomas Fahrenwaldt, Christine Fischer, Abdul Matin, Jamshed Iqbal, Michael Plötz, Jürgen Eberle, Peter Langer
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  ABSTRACT: Selenoindirubins and selenoindirubin-N-glycosides were prepared by the reaction of isatins and isatin-N-glycosides with 3-acetoxy-benzo[b]selenophene, respectively. While selenoindirubin-N-glycosides have not been reported before, three non-glycosylated selenoindirubins were previously reported, but without quantities, yields, scales, experimental details and spectroscopic data. In addition, the work could, in our hands, not be reproduced to prepare pure products. The present paper includes an optimized procedure for the synthesis of selenoindirubins and their complete characterization. Both selenoindirubins and selenoindirubin-N-glycosides showed antiproliferative activity in lung cancer cell lines. In melanoma cells, antiproliferative effects were further accompanied by induced apoptosis in combination with the death ligand TRAIL.
  Organic & Biomolecular Chemistry 05/2013;
• Article: Carboxylation of alkynylsilanes with carbon dioxide mediated by cesium fluoride in DMSO.

  Misato Yonemoto-Kobayashi, Kiyofumi Inamoto, Yoshiyuki Tanaka, Yoshinori Kondo
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  ABSTRACT: The facile syntheses of a variety functionalized propiolic acids were achieved by carboxylation of alkynylsilanes with carbon dioxide mediated by cesium fluoride under ambient conditions.
  Organic & Biomolecular Chemistry 05/2013;
• Article: New meso-substituted trans-A2B2 di(4-pyridyl)porphyrins as building blocks for metal-mediated self-assembling of 4 + 4 Re(i)-porphyrin metallacycles.

  Mariangela Boccalon, Elisabetta Iengo, Paolo Tecilla
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  ABSTRACT: The reaction between 5-(4-pyridyl)dipyrrylmethane and aromatic aldehydes affords meso-arylsubstituted trans-A2B2 di(4-pyridyl)porphyrins which are key building blocks in the metal-mediated self-assembling of supramolecular structures. A careful optimization of the reaction conditions allowed us to obtain 5,15-diphenyl-10,20-di(4-pyridyl)porphyrin (), and two analogues bearing on the meso-phenyl substituents two dipropyl- () or dihexyl-alkyl chains (), with yields ranging from 53 to 63%. Porphyrin reacts with Re(CO5)Br to give the expected 4 + 4 Re(i)-porphyrin metallacycle which has been fully characterized by means of infrared, NMR and UV-Vis (absorption and emission) spectroscopies and by guest inclusion studies. Unexpectedly the addition of alkyl chains to the porphyrin fragment, which increase the solubility of the porphyrin in organic solvents, has the opposite effect on the adduct with Re(i). Indeed, the reaction between Re(CO5)Br and porphyrins gives very insoluble materials, hampering their complete characterization.
  Organic & Biomolecular Chemistry 05/2013;
• Article: O-Benzoxazolyl imidates as versatile glycosyl donors for chemical glycosylation.

  Swati S Nigudkar, Archana R Parameswar, Papapida Pornsuriyasak, Keith J Stine, Alexei V Demchenko
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  ABSTRACT: Herein, we report a new class of glycosyl donors, benzoxazolyl imidates, for chemical glycosylation. The O-benzoxazolyl (OBox) leaving group was designed with an aim to compare the relative reactivity and stability of similarly structured S-benzoxazolyl (SBox) glycosides (thioimidates) developed in our lab and glycosyl trichloroacetimidates (TCAI, O-imidates) developed by Schmidt. Novel OBox donors can be activated under catalytic conditions and provided excellent yields in glycosylation. The OBox imidates were found to be more reactive than either SBox or TCAI donors. The high reactivity profile was confirmed in direct competitive experiments and was found beneficial for HPLC-assisted solid-phase synthesis.
  Organic & Biomolecular Chemistry 05/2013;
• Article: Enantioselective phase-transfer catalytic α-alkylation of 2-methylbenzyl tert-butyl malonates.

  Min Woo Ha, Suckchang Hong, Cheonhyoung Park, Yohan Park, Jihye Lee, Mi-Hyun Kim, Jihoon Lee, Hyeung-Geun Park
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  ABSTRACT: A new asymmetric synthetic method to prepare α,α-dialkylmalonates for the construction of a quaternary carbon center via phase-transfer catalytic (PTC) alkylation has been developed. Enantioselective α-alkylation of 2-methylbenzyl tert-butyl α-methylmalonates under phase-transfer catalytic conditions in the presence of (S,S)-3,4,5-trifluorophenyl-NAS bromide () afforded the corresponding α,α-dialkylmalonates in high chemical (up to 99%) and optical yields (up to 91% ee), which were selectively hydrolyzed to malonic monoacids under alkali basic conditions for conversion to versatile chiral intermediates.
  Organic & Biomolecular Chemistry 05/2013;
• Article: A 'dual click' strategy for the fabrication of bioselective, glycosylated self-assembled monolayers as glycocalyx models.

  Carsten Grabosch, Martin Kind, Yasmin Gies, Felix Schweighöfer, Andreas Terfort, Thisbe K Lindhorst
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  ABSTRACT: Solid surfaces decorated with specific saccharide patterns can serve as a model for the chemically and structurally highly complex glycocalyx of eukaryotic cells. Here we present an approach based on self-assembled monolayers on gold, which are built up in a three-step manner to provide a solid basis, a biorepulsive oligoethylene glycol part, and a specific carbohydrate terminus in a modular way. Of the different reaction sequences, the one with two consecutive 'click reactions' (the copper(i)-catalysed 1,3-dipolar cycloaddition of alkynes with azides and the thiourea-bridging of isothiocyanates with amines) directly 'on SAM' results in the densest layers, as demonstrated by infrared absorption reflection spectroscopy and ellipsometry. As a 'real life' test, the surfaces obtained this way were used for bacterial adhesion experiments. Here the biorepulsivity of the middle part of the SAMs as well as specific binding to the carbohydrate termini could be clearly demonstrated.
  Organic & Biomolecular Chemistry 05/2013;
• Article: Regio- and chemoselective palladium-catalyzed benzylallylation of activated olefins: the remarkable effect of palladium nanoparticles.

  Xuan Zhang, Xiujuan Feng, Xiaoqiang Yu, Ren He, Ming Bao
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  ABSTRACT: The palladium-catalyzed three-component reactions of benzyl halides, activated olefins, and allyltributylstannane were successfully conducted to produce the corresponding benzylallylation products in satisfactory to high yields. The benzylallylation reaction proceeded smoothly under mild conditions in the presence of palladium nanoparticles in tetrahydrofuran.
  Organic & Biomolecular Chemistry 05/2013;
• Article: Stereoselective cross aldol condensation of bicyclo[3.2.0]alkanones.

  Laurence Miesch, Tania Welsch, Michel Miesch
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  ABSTRACT: A cross aldol reaction between [(S)-(-)] or [(R)-(+)]-benzyloxypropanal and silyl enol ethers derived from bicyclo[3.2.0]alkanones was carried out in the presence of TiCl4, leading with total stereoselectivity to a 1 : 1 mixture of enantiomerically pure diastereomers isolated in 81% overall yield. Thus, 5 stereogenic centers could be created starting from one. Furthermore, an efficient access to an enantiomerically pure tricyclo[5.3.0.0(2,6)]decane scaffold was possible via a 4 step reaction sequence.
  Organic & Biomolecular Chemistry 05/2013;
• Article: N-(Guanidinoethyl)-2'-deoxy-5-methylisocytidine exhibits selective recognition of a CG interrupting site for the formation of anti-parallel triplexes.

  Hidenori Okamura, Yosuke Taniguchi, Shigeki Sasaki
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  ABSTRACT: The development of novel nucleoside analogues for the formation of triplex DNA containing pyrimidine-purine inversion sites has been a challenging field. In this paper, we describe the design and synthesis of non-natural nucleoside analogues, N-substituted-2'-deoxy-5-methylisocytidine derivatives, and their evaluation for triplex formation. It has been shown that N-(guanidinoethyl)-2'-deoxy-5-methylisocytidine exhibits selective recognition of a CG interrupting site and potentiates the formation of anti-parallel triplexes.
  Organic & Biomolecular Chemistry 05/2013;
• Article: Formation of C[double bond, length as m-dash]N bonds by the release of H2: a new strategy for synthesis of imines and benzazoles.

  Xukang Jin, Yuxiao Liu, Qiongqiong Lu, Dejun Yang, Jiangkai Sun, Shuangshuang Qin, Jingwu Zhang, Jiaxuan Shen, Changhu Chu, Renhua Liu
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  ABSTRACT: A new strategy for synthesis of imines using the approach of release of H2 has been developed. This oxidant- and acceptor-free Pd/C catalysis protocol is further applied to synthesis of benzoxazoles, benzimidazoles, and benzothiazoles through a one-pot cascade reaction with notably high yields.
  Organic & Biomolecular Chemistry 05/2013;
• Article: From N-benzoylpyridinium imides to pyrazolo[1,5-a]pyridines: a mechanistic discussion on a stoichiometric Cu protocol.

  Lin Ling, Jingqing Chen, Jiahui Song, Yuhai Zhang, Xinqian Li, Lijuan Song, Feng Shi, Yuxue Li, Chunrui Wu
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  ABSTRACT: A Cu-mediated preparation of 2-substitiuted pyrazolo[1,5-a]pyridines from N-benzoylpyridinium imides and terminal alkynes is described using stoichiometric Cu(OAc)2 as both the mediator and the oxidant. Extensive DFT calculations suggest a Cu(iii) intermediate via disproportionation of Cu(ii).
  Organic & Biomolecular Chemistry 05/2013;
• Article: One-pot synthesis of branched oligosaccharides by use of galacto- and mannopyranosyl thioglycoside diols as key glycosylating agents.

  Xing-Yong Liang, Qiang-Wei Liu, Hua-Chao Bin, Jin-Song Yang
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  ABSTRACT: We describe in this paper the efficient four-component one-pot synthesis of three fully protected oligosaccharides , , and with di-branched structures by employing d-galacto- and mannopyranosyl thioglycoside diols as central glycosylating agents. After global deprotection, they were converted respectively into the 3-aminopropyl linker-containing free oligosaccharide fragments , , and structurally related to cell wall oligosaccharides from Atractylodes lancea DC, the marine fungus Lineolata rhizophorae and pathogenic Mycobacterium tuberculosis. The 3-aminopropyl linker at the anomeric carbon can enable conjugation of these synthetic oligomers to a suitable protein carrier.
  Organic & Biomolecular Chemistry 05/2013;
• Article: Determination of the binding epitope of RGD-peptidomimetics to αvβ3 and αIIbβ3 integrin-rich intact cells by NMR and computational studies.

  Ileana Guzzetti, Monica Civera, Francesca Vasile, Elena M Araldi, Laura Belvisi, Cesare Gennari, Donatella Potenza, Roberto Fanelli, Umberto Piarulli
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  ABSTRACT: NMR experiments (transferred NOE and Saturation Transfer Difference) were used to shed light on the binding epitope of RGD peptidomimetics with integrins αvβ3 and αIIbβ3, expressed on the membrane of ECV304 bladder cancer cells and human platelets, respectively. The NMR results were supported by docking calculations of in the active sites of αvβ3 and αIIbβ3 integrin receptors and were compared to the results of competitive αvβ3 receptor binding assays and competitive ECV304 cell adhesion experiments. While cis RGD ligand interacts mainly with the α integrin subunit through its basic guanidine group, trans RGD ligands and are able to interact with both the α and β integrin subunits via an electrostatic clamp.
  Organic & Biomolecular Chemistry 05/2013;