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

• . Unfortunately, only a few of our prepared compounds were sufficiently soluble in water to be suitable for the SPR test. However, a series of other multivalent conjugates was synthesized by using click chemistry with the azide derived from aminopyran 1 and results will be published in due time [40]. Conclusion

Synthesis of a hexasaccharide partial sequence of hyaluronan for click chemistry and more

• Marina Bantzi,
• Stephan Rigol and
• Athanassios Giannis

Beilstein J. Org. Chem. 2015, 11, 604–607, doi:10.3762/bjoc.11.67

• Abstract In the present work, the synthesis of a hexasaccharide partial sequence of hyaluronan equipped with a terminal azido moiety is reported. This hexasaccharide can be used for the attachment on surfaces by means of click chemistry and after suitable deprotection for biophysical studies. Keywords

• : azide; click chemistry; extracellular matrix; hexasaccharide; hyaluronan; multivalency; Introduction Much effort has been exerted during the last years to refine current knowledge about the biology of the extracellular matrix (ECM) [1]. While in the past, it was only regarded as a “space filler” among

• , allowing it to be used for surface modification via click chemistry. After suitable deprotection it can be used for biophysical studies by interaction with an alkyne group of suitably prepared proteins or proteoglycans giving the opportunity to gain deeper insights into ECM processes. Eventually, this

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

• 140, DK-8000 Aarhus, Denmark 10.3762/bjoc.11.58 Abstract A novel β-cyclodextrin (β-CD) dimer was synthesized and surface-grafted by click chemistry onto azide-functionalized quartz surfaces in order to introduce the cooperative features of the β-CD dimer to solid surfaces. Using NMR and fluorescence

• to parent β-CD) for the inclusion of lipophilic molecules [5][9]. The extensive research on the topic has generated a vast number of different β-CD-dimer constructs and methods for the synthesis thereof. Of these methods, synthesis by click chemistry (and specifically the copper(I)-catalyzed azide

Functionalized branched EDOT-terthiophene copolymer films by electropolymerization and post-polymerization “click”-reactions

• Miriam Goll,
• Adrian Ruff,
• Erna Muks,
• Felix Goerigk,
• Beatrice Omiecienski,
• Ines Ruff,
• Rafael C. González-Cano,
• Juan T. Lopez Navarrete,
• M. Carmen Ruiz Delgado and
• Sabine Ludwigs

Beilstein J. Org. Chem. 2015, 11, 335–347, doi:10.3762/bjoc.11.39

• levels. The use of EDOT-N3 as co-monomer furthermore allows modifications of the films by polymer analogous reactions. Here, we exemplarily describe the post-functionalization with ionic moieties by 1,3-dipolar cycloaddition (“click”-chemistry) which allows to tune the surface polarity of the copolymer

• films from water contact angles of 140° down to 40°. Keywords: band-gap engineering; “click”-chemistry; conducting polymers; electropolymerization; Raman spectroscopy; surface functionalization; Introduction The many different applications of conducting polymers demand for tailored properties

• electropolymerized PEDOT-N3 with different redox functionalities as employed by Bäuerle et al. [41][42][43]. The PEDOT relative, propargyl-substituted chemically synthesized 3,4-propylenedioxythiophene was used by Kumar et al. to introduce ionic groups by “click”-chemistry to render the solubility of the gained

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

• by exploiting a click chemistry reaction of 5’-azido-2’-oxa-3’-aza-4’a-carbanucleosides with substituted alkynes. Biological tests indicate an antitumor activity for the synthesized compounds: most of them inhibit cell proliferation of Vero, BS-C-1, HEp-2, MDCK, and HFF cells with a CC50 in the range

• of 5.0–40 μM. The synthesized compounds do not show any antiviral activity. Keywords: antitumor activity; click chemistry; 1,3-dipolar cycloaddition; nucleic acids; 2’-oxa-3’-aza-4’a-carbanucleoside analogs; Introduction Synthetic modified nucleosides are of great interest as potential new lead

• Sharpless [46] (Scheme 1 and Table 1). The click chemistry process, carried out with equimolar amounts of the respective dipolarophiles, afforded in all the cases the corresponding C-5’-triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides 13 and 14 in good yields (79–89%). According to other copper-catalyzed azide

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

• functionalizations in terminal positions. First applications were presented with pyrene, cinnamoyl and anthracenyl labelled ARs. Keywords: articulated rods; click chemistry; molecular rods; oligospiroketals; pyrene excimer; Introduction One of the basic principles in living nature is based on shape-persistent and

Efficient deprotection of F-BODIPY derivatives: removal of BF₂ using Brønsted acids

• Mingfeng Yu,
• Joseph K.-H. Wong,
• Cyril Tang,
• Peter Turner,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2015, 11, 37–41, doi:10.3762/bjoc.11.6

• ) effects this conversion in near-quantitative yields. Compared to existing methods, these conditions are relatively mild and operationally simple, requiring only reaction at room temperature for six hours (TFA) or overnight (HCl). Keywords: Brønsted acids; click chemistry; deboration; dipyrrins; F-BODIPYs

Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase

• María Emilia Cano,
• Rosalía Agusti,
• Alejandro J. Cagnoni,
• María Florencia Tesoriero,
• José Kovensky,
• María Laura Uhrig and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 3073–3086, doi:10.3762/bjoc.10.324

• the bioavailability in vivo [31]. Triazole-substituted β-galactopyranosides and triazole-sialyl mimetics have been synthesized by click chemistry and their inhibitory activity on the hydrolysis of 2’-(4-methylumbelliferyl)-β-D-N-acetylneuraminic acid by TcTS and trypanocidal activity were evaluated

• [32][33]. In the present work, we selected thioglycosidic and N-glycosidic bonds to link the acceptor sugars to a platform by click chemistry, taking into consideration that they are highly resistant to enzymatic hydrolysis [34][35]. We have previously described the synthesis of multivalent β

A small azide-modified thiazole-based reporter molecule for fluorescence and mass spectrometric detection

• Stefanie Wolfram,
• Hendryk Würfel,
• Stefanie H. Habenicht,
• Christine Lembke,
• Phillipp Richter,
• Eckhard Birckner,
• Rainer Beckert and
• Georg Pohnert

Beilstein J. Org. Chem. 2014, 10, 2470–2479, doi:10.3762/bjoc.10.258

• profiling (ABPP); bioorthogonal; click chemistry; mass defect; molecular probe; Introduction Fluorescent dyes are widely used for detection and monitoring in the fields of chemistry, biochemistry, molecular biology, medicine and material sciences. Due to sensitive and selective detection methods and

• fluorophores requires the attachment of the fluorescent reporter to bio(macro)molecules or synthetic probes. Especially “click chemistry”, introduced by Sharpless and coworkers in 2001 [7], is a widely used strategy to attach fluorophores covalently to other molecules. Among "click" reactions the Cu(I

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

• -linking reaction itself is straight-forward, the vinyl-substituted nucleosides need to be chemically synthesized and subsequently converted into their phosphoamidites for chemical DNA synthesis. The same holds true for cross-links based on aldehyde [8][35][36][37] or click chemistry [38]. In addition

Synthesis and optical properties of pyrrolidinyl peptide nucleic acid carrying a clicked Nile red label

• Nattawut Yotapan,
• Chayan Charoenpakdee,
• Pawinee Wathanathavorn,
• Boonsong Ditmangklo,
• Hans-Achim Wagenknecht and
• Tirayut Vilaivan

Beilstein J. Org. Chem. 2014, 10, 2166–2174, doi:10.3762/bjoc.10.224

• , pyrrolidinyl peptide nucleic acid (acpcPNA) was labeled at its backbone with Nile red, a solvatochromic benzophenoxazine dye, by means of click chemistry. The optical properties of the Nile red-labeled acpcPNA were investigated by UV–vis and fluorescence spectroscopy in the absence and in the presence of DNA

• insertion are suggestive of different interactions between the Nile red label and the duplexes. Keywords: click chemistry; deoxyribonucleic acid; DNA bulge; fluorescence; nucleic acids; solvatochromism; Introduction Fluorescent labels are important tools for investigating the structure and dynamics of

• properties. Results and Discussion At least two different means to introduce the Nile red label onto DNA by using click chemistry have been reported in the literature. One involves the clicking of in situ generated 5-azidodeoxyuridine-containing DNA with propargyl Nile red [16], the other employs DNA bearing

Investigations of thiol-modified phenol derivatives for the use in thiol–ene photopolymerizations

• Sebastian Reinelt,
• Monir Tabatabai,
• Urs Karl Fischer,
• Norbert Moszner,
• Andreas Utterodt and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 1733–1740, doi:10.3762/bjoc.10.180

• [13][14], siloranes [15] or spiroorthocarbonates [16] are worth to be mentioned. Since Sharpless et al. published their concept of click chemistry in 2001, these reactions gained growing impact on the design of new materials [17]. Besides the alkyne–azide reaction, especially thiol–ene reactions were

Clicked and long spaced galactosyl- and lactosylcalix[4]arenes: new multivalent galectin-3 ligands

• Silvia Bernardi,
• Paola Fezzardi,
• Gabriele Rispoli,
• Stefania E. Sestito,
• Francesco Peri,
• Francesco Sansone and
• Alessandro Casnati

Beilstein J. Org. Chem. 2014, 10, 1672–1680, doi:10.3762/bjoc.10.175

• . Furthermore, we confirmed that in case of this specific lectin binding the presentation of lactose units on a cone calixarene is highly preferred with respect to its isomeric form in the 1,3-alternate structure. Keywords: glycocalixarenes; cluster glycoside effect; multivalency; click chemistry; surface

• glycocalixarenes “Click Chemistry” [23] reactions are extensively used to conjugate (oligo)saccharides to macrocyclic structures due to the mild conditions and the high yields [24]. For the synthesis of glycocalixarenes the amino–isothiocyanate condensation [25][26][27][28][29][30] or the 1,3-dipolar cycloaddition

Triazol-substituted titanocenes by strain-driven 1,3-dipolar cycloadditions

• Andreas Gansäuer,
• Andreas Okkel,
• Lukas Schwach,
• Laura Wagner,
• Anja Selig and
• Aram Prokop

Beilstein J. Org. Chem. 2014, 10, 1630–1637, doi:10.3762/bjoc.10.169

• active complexes allows the identification of structural features essential for biological activity. Keywords: azides; click-chemistry; cycloadditions; cytotoxicity; titanocenes; Introduction Group 4 metallocenes and derivatives of Cp2TiCl2, in particular, continue to be in the focus of contemporary

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

• anomeric linkages. A library of 80 amphiphiles was subsequently produced, using a 24-vial array, with the majority formed in very good to excellent yields. A preliminary assessment of the liquid-crystalline phase behaviour is also presented. Keywords: amphiphiles; carbohydrates; click chemistry; high

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

• 9-mer 12, 17, and 21 were determined by pulsed-field-gradient-stimulated echo (PFG-STE) NMR experiments and were found to be 3.0, 2.5, and 3.4 nm, respectively. Keywords: carbohydrates; click chemistry; dendrimers; glycodendrimers; lectins; multivalent glycosystems; Introduction Multivalent

• signal (3H) at δ 4.81 ppm and corresponding HRMS data. Zemplén deprotection (NaOMe, MeOH) afforded 5 in 94% yield. Synthesis of the related homolog 9, prepared in 74% overall yield from known 6 [17] by an analogous click chemistry, is also described in Scheme 1. To this end, trichloride 1 was treated as

• shown). Synthesis of mannosylated trimers 5 and 9 using trimesic acid core transformed into propargylated (2) and azidopropylated (6) scaffolds and then coupled by “click chemistry” with either 2-azidoethyl (3) or propargyl (7) mannopyranosides. Divergent CuAAc “click reaction” between propargylated

Pyrene-modified PNAs: Stacking interactions and selective excimer emission in PNA₂DNA triplexes

• Alex Manicardi,
• Lucia Guidi,
• Alice Ghidini and
• Roberto Corradini

Beilstein J. Org. Chem. 2014, 10, 1495–1503, doi:10.3762/bjoc.10.154

• click chemistry or as a masked amino group both in a PNA monomer and in PNA oligomers, allowing to produce a variety of modified PNAs from a single precursor [35]. This chemistry introduces a moderate degree of flexibility which can be useful for allowing interactions with other groups to occur within

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

• photo resistance. Keywords: click chemistry; energy transfer; fluorophore; monosaccharide; photochromism; Introduction The development of functional nanomaterials is nowadays a very attractive field of fundamental and applied research. The chemical functions at the molecular level yield properties

• because sophisticated multistep experimental procedures are often implicated. Recently, the Cu(I)-catalyzed alkyne–azide cycloaddition reaction (CuAAC, an excellent example of click chemistry) has been demonstrated as a robust and highly efficient ligation tool to conjugate various azido- and alkyne

• -functionalized moieties [18][19][20]. Monosaccharides can be readily functionalized with several propargyl groups to synthesize, using click chemistry, multivalent neoglycoconjugates for recognition studies with carbohydrate-binding proteins (lectins) [21][22][23][24] or to develop light-harvesting antenna

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

• -caprolactone for targeting dendritic cells and macrophages (Figure 4) [45] Both mannose and galactose were attached to PEGylated nanoparticles by click-chemistry between their propargyl glycosides and a gold nanoparticles derivatized with an azide-functionalized PEG [46]. Also, several unprotected carbohydrate

• units of mannose, fucose or lactose, have been incorporated into the surface of PEGylated dendritic polymers by means of click chemistry. The larger dendrimer generations have demonstrated an increased capacity to aggregate lectins [47]. Analogs of lactose have been reported as inhibitors of the enzyme

An economical and safe procedure to synthesize 2-hydroxy-4-pentynoic acid: A precursor towards ‘clickable’ biodegradable polylactide

• Quanxuan Zhang,
• Hong Ren and
• Gregory L. Baker

Beilstein J. Org. Chem. 2014, 10, 1365–1371, doi:10.3762/bjoc.10.139

• onto polymers from a single monomer via convenient ‘click’ chemistry with organic azides. The incorporation of various pendant functional groups could effectively tailor the physicochemical properties of polylactide. The reported synthesis of 1 started from propargyl bromide and ethyl glyoxylate

• hydroxylation of propargylic malonate 5 without work-up of any intermediate. Keywords: alkylation; ‘click’ chemistry; ‘clickable’ polylactide; decomposition; diethyl 2-acetamidomalonate; 2-hydroxy-4-pentynoic acid; one-pot; optimization; propargyl bromide; propargyl tosylate; safe and economical; Introduction

• groups onto polymers via convenient ‘click’ reaction with organic azido molecules without PLA backbone degradation [17]. ‘Click’ chemistry [20], which is copper(I)-catalyzed 1,3-dipolar cycloaddition of azides and alkynes, has been developed and utilized in recent years as a powerful synthetic strategy

Design and synthesis of multivalent neoglycoconjugates by click conjugations

• Feiqing Ding,
• Li Ji,
• Ronny William,
• Hua Chai and
• Xue-Wei Liu

Beilstein J. Org. Chem. 2014, 10, 1325–1332, doi:10.3762/bjoc.10.134

• few examples of oligosaccharides and glycopeptides mimics have so far been prepared by a click chemistry strategy [40][41][42][43][44][45][46][47][48]. Most recently, we developed a strategy for the synthesis of 3-amino-2,3-dideoxysugars using a regio- and stereoselective tandem hydroamination

• “click chemistry” in the glycosylation reactions, we aspired to apply the highly efficient triazole formation employing an azide 3 and a suitable alkyne appended to the 3-amino-2,3-dideoxysugars moiety 2 (Figure 3). In continuation of our previous work, herein we report a direct and reliable synthetic

Synthesis, characterization and DNA interaction studies of new triptycene derivatives

• Sourav Chakraborty,
• Snehasish Mondal,
• Rina Kumari,
• Sourav Bhowmick,
• Prolay Das and
• Neeladri Das

Beilstein J. Org. Chem. 2014, 10, 1290–1298, doi:10.3762/bjoc.10.130

• various interesting applications in organic chemistry [9][10][11] as well as material science [12][13][14][15] and drug discovery [16][17][18]. Organic azides in general are popular in recent times because of their use as synthons in Cu(I)-catalyzed “click chemistry” [19]. It is also well known that

Polyglycerol-functionalized nanodiamond as a platform for gene delivery: Derivatization, characterization, and hybridization with DNA

• Li Zhao,
• Yuki Nakae,
• Hongmei Qin,
• Tadamasa Ito,
• Takahide Kimura,
• Hideto Kojima,
• Lawrence Chan and
• Naoki Komatsu

Beilstein J. Org. Chem. 2014, 10, 707–713, doi:10.3762/bjoc.10.64

• confirmed by gel retardation assay that ND-PG-Arg8 and ND-PG-Lys8 with higher zeta potential hybridized with plasmid DNA (pDNA) through electrostatic attraction, making them promising as nonviral vectors for gene delivery. Keywords: carbon-nanomaterials; click chemistry; DNA; gene delivery; nanodiamond

• , Lys8 and His8) through click chemistry followed by hybridization with plasmid DNA (pDNA) and its characterization by electrophoresis is reported. Results and Discussion Preparation and characterization of ND50-PG In view of actual cancer therapy utilizing the enhanced permeation and retention (EPR

• distance in the STEM image (Figure 4b) as mentioned above. Immobilization of basic polypeptides through click chemistry The PG layer including a large number of hydroxy groups endows ND50-PG not only with very high hydrophilicity (Figure 5), but also with a versatile platform for further surface

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

• ; antitumor agents; click chemistry; mutasynthesis; natural products; Introduction Although natural products and analogues cover a large portion of the drug market particularly in the treatment of cancer as well as bacterial and viral infections their role in pharmaceutical research has decreased over the

• cycloadditions better known as “copper mediated Click-chemistry” while alkenes, especially vinyl- and allylbenzoic systems, are predestined for being utilized in cross metathesis reactions. Therefore a series of aminobenzoic acids 9–20 (Figure 1) were prepared (see Supporting Information File 1). We expected

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• without a significant loss of its catalytic activity. Similar PS–NHC–silver complexes were recently prepared via click-chemistry, and their aptitude to catalyze A3-coupling was verified [13]. The suitability of NHC–Ag(I) complexes as catalysts for A3-coupling MCR was confirmed, and independently developed