Creating molecular macrocycles for anion recognition

• Amar H. Flood

Beilstein J. Org. Chem. 2016, 12, 611–627, doi:10.3762/bjoc.12.60

• activity surrounding 1,2,3-triazoles made using click chemistry; and the same triazoles are responsible for anion capture. Mistakes made and lessons learnt in anion recognition provide deeper understanding that, together with theory, now provides for computer-aided receptor design. The lessons are acted

• philosophy for synthetic design that was derived from Roald Hoffmann’s idea of chemistry being “the same and not the same” [9]. At around this time (2006), click chemistry [10] (Figure 3) had caught my attention for its prevalence but I did not know why it was being used so much. All I could venture was that

• it was an old reaction, the Huisgen cycloaddition, made good (regioselective) with the aid of copper catalysis. Taking that idea on face value, I reasoned that click chemistry was a new and extremely effective way to make 1,2,3-triazoles. It is not often that either new or newly refined reactions

Exploring architectures displaying multimeric presentations of a trihydroxypiperidine iminosugar

• Camilla Matassini,
• Stefania Mirabella,
• Andrea Goti,
• Inmaculada Robina,
• Antonio J. Moreno-Vargas and
• Francesca Cardona

Beilstein J. Org. Chem. 2015, 11, 2631–2640, doi:10.3762/bjoc.11.282

• , Universidad de Sevilla, c/ Prof. García González 1, E-41012, Sevilla, Spain 10.3762/bjoc.11.282 Abstract The synthesis of new multivalent architectures based on a trihydroxypiperidine α-fucosidase inhibitor is reported herein. Tetravalent and nonavalent dendrimers were obtained by means of the click

• chemistry approach involving the copper azide-alkyne-catalyzed cycloaddition (CuAAC) between suitable scaffolds bearing terminal alkyne moieties and an azido-functionalized piperidine as the bioactive moiety. A preliminary biological investigation is also reported towards commercially available and human

Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry

• Zhan-Jiang Zheng,
• Ding Wang,
• Zheng Xu and
• Li-Wen Xu

Beilstein J. Org. Chem. 2015, 11, 2557–2576, doi:10.3762/bjoc.11.276

• Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou, P. R. China 10.3762/bjoc.11.276 Abstract The Cu(I)-catalyzed azide-alkyne cycloaddition reaction, also known as click chemistry, has become a useful tool for the facile formation of 1,2,3-triazoles

• . Specifically, the utility of this reaction has been demonstrated by the synthesis of structurally diverse bi- and bis-1,2,3-triazoles. The present review focuses on the synthesis of such bi- and bistriazoles and the importance of using copper-promoted click chemistry (CuAAC) for such transformations. In

• addition, the application of bitriazoles and the related CuAAAC reaction in different fields, including medicinal chemistry, coordination chemistry, biochemistry, and supramolecular chemistry, have been highlighted. Keywords: bistriazoles; click chemistry; cycloaddition; homogeneous catalysis; oxidative

Easy access to heterobimetallic complexes for medical imaging applications via microwave-enhanced cycloaddition

• Nicolas Desbois,
• Sandrine Pacquelet,
• Adrien Dubois,
• Clément Michelin and
• Claude P. Gros

Beilstein J. Org. Chem. 2015, 11, 2202–2208, doi:10.3762/bjoc.11.239

• are promising contrast agents (CA) in MRI. Keywords: click chemistry; corrole; DOTA; microwave; NOTA; porphyrin; Introduction Magnetic resonance imaging (MRI), positron emission tomography (PET) or single photon emission computed tomography (SPECT) are actually the most commonly used imaging

• (e.g., pH fix at 7 for Cu2+ and pH fix at 3 for Ga3+). The isolated copper and gallium NOTA derivatives 12a,b were characterized by high-resolution mass spectrometry. Scope of the cycloaddition reaction Over the past decade, click chemistry has been applied to the synthesis of a wide variety of

• click chemistry have shown significant advantages over traditional procedures for the modular, rapid, clean, and efficient synthesis of potential radiopharmaceuticals. In this regard, click chemistry has already begun to revolutionize radiopharmaceutical chemistry. The method reported herein provided

Effective ascorbate-free and photolatent click reactions in water using a photoreducible copper(II)-ethylenediamine precatalyst

• Redouane Beniazza,
• Natalia Bayo,
• Florian Molton,
• Carole Duboc,
• Stéphane Massip,
• Nathan McClenaghan,
• Dominique Lastécouères and
• Jean-Marc Vincent

Beilstein J. Org. Chem. 2015, 11, 1950–1959, doi:10.3762/bjoc.11.211

• photogenerated copper(I) being very reactive. On irradiating aqueous reaction mixtures containing 1 mol % of 1 at 365 nm (TLC lamp) for 1 h, click reactions were shown to proceed to full conversion. Keywords: benzophenone photosensitizer; bioconjugation; click chemistry; copper; photoreduction; Introduction

• organic solvents, typically MeOH, THF or toluene. It should be noted that within the last four years, other photoreducible copper(II)-based catalytic systems applied to click chemistry have been reported [15][16][17][18][19][20][21][22][23][24][25][26][27], in particular for the preparation of polymers

Synthesis and spectroscopic properties of β-triazoloporphyrin–xanthone dyads

• Dileep Kumar Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2015, 11, 1434–1440, doi:10.3762/bjoc.11.155

• -diethynylxanthen-9-one. In addition, a new series of various β-triazole-linked porphyrin–xanthone conjugates and xanthone-bridged triazoloporphyrin dyads were synthesized through click chemistry in moderate to good yields. The preliminary photophysical evaluation of these π-conjugated molecules revealed a

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

• 308 in the presence of CuSO4 and sodium ascorbate in acetonitrile/water to deliver the desired cyclophane derivative 309 (56%, Scheme 53). Similarly, a novel BINOL-based cyclophane 310 has been synthesized via click chemistry by incorporating two triazole moieties in the macrocycle [187]. Li and co

Quarternization of 3-azido-1-propyne oligomers obtained by copper(I)-catalyzed azide–alkyne cycloaddition polymerization

• Shun Nakano,
• Akihito Hashidzume and
• Takahiro Sato

Beilstein J. Org. Chem. 2015, 11, 1037–1042, doi:10.3762/bjoc.11.116

• alkynes with a copper(I) catalyst under mild conditions even in the presence of various functional groups [1][2][3]. CuAAC is thus the most important reaction in “click chemistry” [4][5][6][7]. A number of studies have been published on CuAAC, which is applied in a wide range of fields from bio-related

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