Synthesis of enantiopure sugar-decorated six-armed triptycene derivatives

• Paola Bonaccorsi,
• Maria Luisa Di Gioia,
• Antonella Leggio,
• Lucio Minuti,
• Teresa Papalia,
• Carlo Siciliano,
• Andrea Temperini and
• Anna Barattucci

Beilstein J. Org. Chem. 2013, 9, 2410–2416, doi:10.3762/bjoc.9.278

• fully characterized. Keywords: azide derivatives; click chemistry; glycoconjugates; 2-propyn-1-yl β-D-glycopyranosides; triptycene; Introduction Triptycene (1), with its three arene units fused to the bicyclo[2.2.2]octa-2,5,7-triene system appears as a paddle wheel on closer inspection (Figure 1). The

• chemistry, can be easily applied for decorating even complex molecular systems. The reaction can be conducted in various solvents and is compatible with several functional groups. The obtained triazole ring is as stable as the most common amide bonds [15][16][17]. Thus, we decided to use click chemistry for

• is the first example of six-armed carbohydrate-substituted triptycenes, which appear as promising candidates for the development of new supramolecular systems with specific properties. Results and Discussion The Huisgen 1,3-dipolar cycloaddition reaction, which represents the key step of click

Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

• Sándor B. Ötvös,
• Ádám Georgiádes,
• István M. Mándity,
• Lóránd Kiss and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1508–1516, doi:10.3762/bjoc.9.172

• safe and straightforward way. The obtained 1,2,3-triazole-substituted β-aminocyclohexanecarboxylates can be regarded as interesting precursors for drugs with possible biological effects. Keywords: β-amino acids; click chemistry; continuous-flow; copper; flow chemistry; triazoles; Introduction In

• relatively short reaction time [18][19][20]. Recently, Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) has become the basis of the so-called click chemistry concept due to its wide applicability and efficiency. Over the past twenty years, alicyclic β-amino acids have attracted great interest among

Methylidynetrisphosphonates: Promising C₁ building block for the design of phosphate mimetics

• Vadim D. Romanenko and
• Valery P. Kukhar

Beilstein J. Org. Chem. 2013, 9, 991–1001, doi:10.3762/bjoc.9.114

• ethenylidenebisphosphonate 13 and the subsequent phosphinylation and oxidation (Scheme 7). This compound has been used in an elegant construction (“click” chemistry) of triazole derivatives (see Scheme 17) [26][28]. Synthesis via 7,7-bisphosphonoquinone methides A unique route to trisphosphonate 18 via addition of diethyl

Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway

• Jessica L. Bell,
• Andrew J. Haak,
• Susan M. Wade,
• Yihan Sun,
• Richard R. Neubig and
• Scott D. Larsen

Beilstein J. Org. Chem. 2013, 9, 966–973, doi:10.3762/bjoc.9.111

• click chemistry. All were confirmed to maintain biological activity in a cell-based assay for inhibition of SRE-Luc expression. The functional activity of the most potent probe 24 was further confirmed in an assay for PC-3 cell migration. Photolysis of 24 in intact PC-3 cells followed by cell lysis

• isolation and/or visualization (e.g., biotin or fluorophore) via click chemistry. This technology has been highly successful in profiling enzyme activity in living cells and even in whole organisms [21]. In ABPP, covalent linkage by the reactive functionality is usually dependent upon a particular enzymatic

• . Following exposure to UV light, the cells would be lysed, releasing the labeled proteins bound covalently to the probe (B). Click chemistry would then be applied to covalently attach a biotin or fluorescent tag for visualization and/or isolation (C). Any isolated proteins would be digested and identified by

Superstructures of fluorescent cyclodextrin via click-reaction

• Arkadius Maciollek,
• Helmut Ritter and
• Rainer Beckert

Beilstein J. Org. Chem. 2013, 9, 827–831, doi:10.3762/bjoc.9.94

• opens up a wide field of modification through click chemistry with azides or thioles [6][7]. Accordingly, following our former work with mono azide modified CD, we were encouraged to combine the fluorescent hydroxythiazole dye with CD [8][9][10]. Such water soluble spectroscopically active hosts can be

• diameter of randomly methylated β-CD, blue: mixture of monomer and oligomer after adding potassium adamantane-1-carboxylate, red: supramolecular polymer of 3. AF4 elution diagram of 3. Synthesis of fluorescent cyclodextrin 3 by click-chemistry.

Towards a biocompatible artificial lung: Covalent functionalization of poly(4-methylpent-1-ene) (TPX) with cRGD pentapeptide

• Lena Möller,
• Christian Hess,
• Jiří Paleček,
• Yi Su,
• Axel Haverich,
• Andreas Kirschning and
• Gerald Dräger

Beilstein J. Org. Chem. 2013, 9, 270–277, doi:10.3762/bjoc.9.33

• , leads to a highly biocompatible poly(methylpentene) surface. The resulting modified membrane preserves the required excellent gas-flow properties while being densely seeded with lung endothelial cells. Keywords: click chemistry; growth factor; nitrenes; plasma chemistry; poly(4-methylpent-1-ene

• glycol) linker, which served as a spacer unit between the polymer and the bioactive cRGD domain [15]. As the final coupling strategy, we chose the Huisgen-type azide–alkyne-“click”-chemistry for which connecting elements 5 and 6 were coupled to polymer derivative 4. Classically, copper catalysts are

• , by the use of Huisgen-type “click” chemistry (Scheme 2). cRGD pentapeptide 1b was prepared in sufficient amounts by solution-phase chemistry [23]. Because of the disadvantage associated with copper-mediated 1,3-cycloadditions of alkynes with azides in biological or biomedical applications we

Peptoids and polyamines going sweet: Modular synthesis of glycosylated peptoids and polyamines using click chemistry

• Daniel Fürniss,
• Timo Mack,
• Frank Hahn,
• Sidonie B. L. Vollrath,
• Katarzyna Koroniak,
• Ute Schepers and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 56–63, doi:10.3762/bjoc.9.7

• azide alkyne cycloadditions. In addition, the up-scaling of some particular azide-modified sugars is described. Keywords: click chemistry; glycans; peptoids; polyalkynes; polyamines; solid-phase chemistry; Introduction To date, oligosaccharides have gained more and more interest as potential drugs in

New enzymatically polymerized copolymers from 4-tert-butylphenol and 4-ferrocenylphenol and their modification and inclusion complexes with β-cyclodextrin

• Adam Mondrzyk,
• Beate Mondrzik,
• Sabrina Gingter and
• Helmut Ritter

Beilstein J. Org. Chem. 2012, 8, 2118–2123, doi:10.3762/bjoc.8.238

• subsequent click chemistry with N3-β-CD. The covalently bound cyclodextrin moiety and the covalently bound Fc or tert-butyl group form host/guest complexes as proven by DLS measurement. The cyclic voltammetry data shows that the central iron atom of the Fc moiety is present in the copolymer and can be

The Amadori rearrangement as glycoconjugation method: Synthesis of non-natural C-glycosyl type glycoconjugates

• Katharina Gallas,
• Gerit Pototschnig,
• Florian Adanitsch,
• Arnold E. Stütz and
• Tanja M. Wrodnigg

Beilstein J. Org. Chem. 2012, 8, 1619–1629, doi:10.3762/bjoc.8.185

• communication. In order to investigate and elucidate their many functions, reliable synthetic methods for the conjugation of carbohydrates to biomolecules are of crucial importance [2]. Several ligation strategies are described in the literature, such as chemical ligation [3], conjugation by means of click

• chemistry (Huisgen cycloaddition) [4][5], glycosylation protocols [6][7], and Staudinger ligation [8], just to mention the most prominent examples. However, many applications in this respect require a ligation method that is functional in aqueous medium, and, for economic purposes in general, protecting

Synthesis of trifunctional cyclo-β-tripeptide templates

• Frank Stein,
• Tahir Mehmood,
• Tilman Plass,
• Javid H. Zaidi and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2012, 8, 1576–1583, doi:10.3762/bjoc.8.180

• containing an additional azide moiety, e.g., for ligation with click chemistry. Synthesis of cyclic peptides employing the oxidation-labile aryl hydrazide linker [11][24]. Functionalization of the cyclic β-tripeptide 4. Acknowledgements Financial support from the Deutsche Forschungsgemeinschaft (Research

High-affinity multivalent wheat germ agglutinin ligands by one-pot click reaction

• Henning S. G. Beckmann,
• Heiko M. Möller and
• Valentin Wittmann

Beilstein J. Org. Chem. 2012, 8, 819–826, doi:10.3762/bjoc.8.91

• enhancements of the multivalent ligands with their ability to bind to the protein in a chelating mode. The best WGA ligand is a trivalent cluster with an IC50 value of 220 nM. Calculated per mol of contained chitobiose, this is the best WGA ligand known so far. Keywords: carbohydrates; click chemistry

Synthetic glycopeptides and glycoproteins with applications in biological research

• Ulrika Westerlind

Beilstein J. Org. Chem. 2012, 8, 804–818, doi:10.3762/bjoc.8.90

• resistant to tumor growth compared to control mice [37]. Vaccines with multivalent MUC1 T- and TN-glycopeptides were efficiently conjugated through azide/alkyne click chemistry to the Pam3CSK4 lipopeptide immune-stimulant. The recently reported vaccines are currently under immunological investigation [38

Chemo-enzymatic modification of poly-N-acetyllactosamine (LacNAc) oligomers and N,N-diacetyllactosamine (LacDiNAc) based on galactose oxidase treatment

• Christiane E. Kupper,
• Ruben R. Rosencrantz,
• Birgit Henßen,
• Helena Pelantová,
• Stephan Thönes,
• Anna Drozdová,
• Vladimir Křen and
• Lothar Elling

Beilstein J. Org. Chem. 2012, 8, 712–725, doi:10.3762/bjoc.8.80

• subtle modifications, such as an aldehyde group [65][66]. Terminal and internal aldehyde groups could be further used for the introduction of different functionalities, such as alkyne or azide groups, to facilitate orthogonal click-chemistry reactions [67]. Moreover, branched poly-LacNAc glycan

Thiophene-based donor–acceptor co-oligomers by copper-catalyzed 1,3-dipolar cycloaddition

• Stefanie Potratz,
• Amaresh Mishra and
• Peter Bäuerle

Beilstein J. Org. Chem. 2012, 8, 683–692, doi:10.3762/bjoc.8.76

• -triazole co-oligomers were investigated by UV–vis spectroscopy and cyclic voltammetry. Several co-oligomers were electropolymerized to the corresponding conjugated polymers. Keywords: acetylene; azide; click chemistry; thiophene; triazole; Introduction Oligo- and polythiophenes are among the most

• popular and reached high significance in materials synthesis, because high yields and easy to purify products are typically obtained [13][14]. The click chemistry approach was successfully employed to synthesize various oligomers [15][16][17], catenanes and rotaxanes [18], dendrimers [11][19][20], and

• 1,2,3-triazole rings as acceptors to conveniently build up novel donor–acceptor co-oligomeric and copolymeric materials by click chemistry. Thereby, the inherent instability of 2-azidothiophene was a problem. Results and discussion In 2005, Liang et al. [32] described a mild, copper-catalyzed method to

Synthesis of heteroglycoclusters by using orthogonal chemoselective ligations

• Baptiste Thomas,
• Michele Fiore,
• Isabelle Bossu,
• Pascal Dumy and
• Olivier Renaudet

Beilstein J. Org. Chem. 2012, 8, 421–427, doi:10.3762/bjoc.8.47

• : chemoselective ligation; click chemistry; cyclopeptide; heteroglycocluster; oxime; Introduction Multivalent interactions between carbohydrates and proteins play key roles in diverse biological events, including fertilization, cell–cell communication, host–pathogen interactions, immune response and cancer

Syntheses and applications of furanyl-functionalised 2,2’:6’,2’’-terpyridines

• Jérôme Husson and
• Michael Knorr

Beilstein J. Org. Chem. 2012, 8, 379–389, doi:10.3762/bjoc.8.41

• electrophilic thiocyanato group and a nucleophilic residue present on the biomolecule (amine, thiol, for example) should allow anchorage of 62. Another approach that was envisioned for the linking of fluorescent europium–terpyridine complexes to biomolecules is the use of click chemistry [54]. Again, 54 was

• -functionalised tpys as potential biomolecule-labelling agents. Synthetic sequence envisioned for biomolecules labelling by click-chemistry. Influence of solvent on U/S ratio. Complexes obtained by direct oxidation of furanyl-functionalised tpys. GI50 (μg/ml) for terpyridines 12 and 13 compared to doxorubicin

Fifty years of oxacalix[3]arenes: A review

• Kevin Cottet,
• Paula M. Marcos and
• Peter J. Cragg

Beilstein J. Org. Chem. 2012, 8, 201–226, doi:10.3762/bjoc.8.22

• conformer by employing “click” chemistry (Scheme 21) [89]. One interesting aspect of the synthesis was that the tris(propargyl) click precursor crystallized as a mixture of cone and partial-cone conformers, yet addition of n-BuNH3+ClO4− to the conformers in solution pushed the equilibrium towards the cone

Synthesis of 2-amino-3-arylpropan-1-ols and 1-(2,3-diaminopropyl)-1,2,3-triazoles and evaluation of their antimalarial activity

• Matthias D’hooghe,
• Stéphanie Vandekerckhove,
• Karen Mollet,
• Karel Vervisch,
• Stijn Dekeukeleire,
• Liesbeth Lehoucq,
• Carmen Lategan,
• Peter J. Smith,
• Kelly Chibale and
• Norbert De Kimpe

Beilstein J. Org. Chem. 2011, 7, 1745–1752, doi:10.3762/bjoc.7.205

• substrates to perform “click chemistry” [34] incorporate an azide group and an aziridine ring in their structure, for example in 2-(azidomethyl)aziridines, thus providing a direct access to 2-[(1,2,3-triazol-1-yl)methyl]aziridines through Cu-catalyzed reaction with alkynes [35]. In this work, nonactivated N

Advances in synthetic approach to and antifungal activity of triazoles

• Kumari Shalini,
• Nitin Kumar,
• Sushma Drabu and
• Pramod Kumar Sharma

Beilstein J. Org. Chem. 2011, 7, 668–677, doi:10.3762/bjoc.7.79

• -lactams and terminal alkynes of bile acids in the presence of a Cu(I) catalyst (click chemistry) by Vatmurge et al. The synthesized compounds were evaluated for their antifungal activity against different fungal strains such as Candida albicans, Cryptococcus neoformans, Benjaminiella poitrasii, Yarrowia

Calix[4]arene-click-cyclodextrin and supramolecular structures with watersoluble NIPAAM-copolymers bearing adamantyl units: “Rings on ring on chain”

• Bernd Garska,
• Monir Tabatabai and
• Helmut Ritter

Beilstein J. Org. Chem. 2010, 6, 784–788, doi:10.3762/bjoc.6.83

• supramolecular complex formation with poly(NIPAAM) bearing attached adamantyl units was investigated by dynamic light scattering (DLS) and turbidity measurements. Keywords: β-cyclodextrin; calix[4]arene; click chemistry; poly(NIPAAM); Introduction Supramolecular interactions of macrocycles with different types

• progress in the field of supramolecular chemistry is based on click chemistry, a versatile and powerful tool that permits the modular assembly of new molecular entities [6][7]. Both CDs as well as calixarenes have already been modified by click chemistry [8][9][10][11][12][13][14]. However, the coupling of

• × 10−3 mmol) was added and the solution was mechanical stirred for 24 h. This solution was centrifuged to remove undissolved particles. Synthesis of calixarene-click-cyclodextrin 4 via click chemistry and structure of copolymer 5. Superstructure of calixarene-click-cyclodextrin 4 and copolymer 5

Synthesis and crossover reaction of TEMPO containing block copolymer via ROMP

• Olubummo Adekunle,
• Susanne Tanner and
• Wolfgang H. Binder

Beilstein J. Org. Chem. 2010, 6, No. 59, doi:10.3762/bjoc.6.59

• -“click”-chemistry [14][15][16][17], the crossover reaction of more complex monomers remains the crucial factor in achieving defined BCP’s with low polydispersities. In a recent example, the crossover reaction of various monomers with the Grubbs’ type catalysts G1–G3 was studied in detail via MALDI mass

New amphiphilic glycopolymers by click functionalization of random copolymers – application to the colloidal stabilisation of polymer nanoparticles and their interaction with concanavalin A lectin

• Otman Otman,
• Paul Boullanger,
• Eric Drockenmuller and
• Thierry Hamaide

Beilstein J. Org. Chem. 2010, 6, No. 58, doi:10.3762/bjoc.6.58

• et Supramoléculaires (ICBMS), Chimie Organique 2 – Glycochimie, UMR CNRS 5246, CPE-Lyon. 43, boulevard du 11 Novembre 1918, Villeurbanne, F-69622, France 10.3762/bjoc.6.58 Abstract Glycopolymers with mannose units were readily prepared by click chemistry of an azido mannopyranoside derivative and a

• . Keywords: click chemistry; con A lectin; dynamic light scattering; glycopolymer; polymer nanoparticles; Introduction Over the last decades, research efforts in pharmaceutical, food and cosmetics technologies have been directed not only towards the syntheses of new bioactive entities or medicines, but also

• polymerization and click chemistry has been reported [8][9]. Besides homopolymers or block copolymers, statistical copolymers obtained from conventional radical polymerization deserve special attention because of their ease of synthesis. Well controlled MW as well as narrow PI are not always pre-requisites to

Bioorthogonal metabolic glycoengineering of human larynx carcinoma (HEp-2) cells targeting sialic acid

• Arne Homann,
• Riaz-ul Qamar,
• Sevnur Serim,
• Petra Dersch and
• Jürgen Seibel

Beilstein J. Org. Chem. 2010, 6, No. 24, doi:10.3762/bjoc.6.24

• )neuraminic acid (Neu5Hex) into the cell-surface glycocalyx of a human larynx carcinoma cell line (HEp-2) and its fluorescence labelling by click chemistry. Keywords: bioorthogonal metabolic glycoengineering; click chemistry; sialic acid; Introduction The surface of eukaryotic cells is heavily covered with

Synthetic incorporation of Nile Blue into DNA using 2′-deoxyriboside substitutes: Representative comparison of (R)- and (S)-aminopropanediol as an acyclic linker

• Daniel Lachmann,
• Sina Berndl,
• Otto S. Wolfbeis and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2010, 6, No. 13, doi:10.3762/bjoc.6.13

• Nile Blue chromophore was incorporated into oligonucleotides using “click” chemistry for the postsynthetic modification of oligonucleotides. These were synthesized using DNA building block 3 bearing an alkyne group and reacted with the azide 4. (R)-3-amino-1,2-propanediol was applied as the linker

• at the same time – Sharpless [16] had reported that the addition of Cu(I) led to a significant increase in the reaction rate and in regioselectivity. This type of “click” chemistry matches the requirements of bioorthogonality since both two functional groups, alkyne and azide, are typically not

• modeling helps to rationalize the experimental result which is the similarity of the optical properties between the two duplexes. Conclusion “Click” chemistry allows the postsynthetic modification of oligonucleotides that were presynthesized using the DNA building block 3 bearing an alkyne group and the

Synthesis of 2-substituted 9-oxa-guanines {5-aminooxazolo[5,4-d]pyrimidin- 7(6H)-ones} and 9-oxa-2-thio- xanthines {5-mercaptooxazolo[5,4-d]pyrimidin- 7(6H)-ones}

• Subrata Mandal,
• Wen Tai Li,
• Yan Bai,
• Jon D. Robertus and
• Sean M. Kerwin

Beilstein J. Org. Chem. 2008, 4, No. 26, doi:10.3762/bjoc.4.26

• preparation of a series of 2-substituted 5-aminooxazolo[5,4-d]pyrimidin-7(6H)-ones and related 5-thio-oxazolo[5,4-d]pyrimidines is described, including analogs suitable for further elaboration employing “click” chemistry utilizing copper-catalyzed Huisgen 1,3-dipolar cycloadditions. Two of the compounds

• prepared were found to inhibit ricin with IC50 ca. 1–3 mM. Keywords: Annulation; Click Chemistry; Cyclization; Purine Analogs; Ricin; Introduction Oxazolo[5,4-d]pyrimidines have been reported to possess a variety of biological activities including kinase inhibition [1][2], adenosine receptor antagonism

• preparation of analogs suitable for further elaboration, for example by “click” chemistry employing copper-catalyzed Huisgen 1,3-dipolar cycloadditions [18]. Results and Discussion Our previous route [5] to 8-methyl-9-oxa-guanine (2a) involved the thermal cyclodehydration of 5-(acetylamino)-2-amino-4,6