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

• have been widely studied in their scope and limitations [10][31]. In particular, the Huisgen cycloaddition reaction was first applied to a calixarene in 2000 by Santoyo-González [32]. Later on, Marra et al. [33] demonstrated that the copper-catalyzed azide–alkyne cycloaddition (CuAAC) [34][35] at room

Photoswitchable precision glycooligomers and their lectin binding

• Daniela Ponader,
• Sinaida Igde,
• Marko Wehle,
• Katharina Märker,
• Mark Santer,
• David Bléger and
• Laura Hartmann

Beilstein J. Org. Chem. 2014, 10, 1603–1612, doi:10.3762/bjoc.10.166

• block AZO. TDS allows for the conjugation of sugar azide ligands via the copper-catalyzed azide–alkyne cycloaddition (CuAAC). The synthesis and coupling on solid support of TDS and EDS has been previously described [7][10]. AZO was synthesized via Mills coupling adapting literature protocols [20][21][22

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

• organic amphiphilic compounds was synthesised consisting of glucose, galactose, lactose, xylose and mannose head groups and double and triple-chain hydrophobic tails. A modular, high-throughput approach was developed, whereby head and tail components were conjugated using the copper-catalysed azide–alkyne

• delivery. Many other fields have utilised the copper-catalysed azide–alkyne cycloaddition (CuAAC) ‘click’ reaction [16][17] to generate libraries of compounds, including enzyme inhibitors [18][19][20], catalysis ligands [21][22][23] and metal frameworks [24][25]. We have recently demonstrated that a

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

• separating the anomeric and the core carbons, were synthesized using azide–alkyne cycloaddition (CuAAc). Compound 23 was prepared by an efficient convergent strategy. The sugar precursors consisted of either a 2-azidoethyl (3) or a prop-2-ynyl α-D-mannopyranoside (7) derivative. The solvodynamic diameters of

• above with 3-azido-1-propanamine to provide 6 in 87% yield. Azide–alkyne cycloaddition of 6 with prop-2-ynyl α-D-mannopyranoside 7 [35] gave 8 (79%) which was de-O-acetylated under Zemplén conditions (NaOMe, MeOH, 95%) to give 9. The syntheses of 9-mers 12, 17 and 21 are illustrated in Schemes 2–5 and

Synthesis of the first examples of iminosugar clusters based on cyclopeptoid cores

• Mathieu L. Lepage,
• Alessandra Meli,
• Anne Bodlenner,
• Céline Tarnus,
• Francesco De Riccardis,
• Irene Izzo and
• Philippe Compain

Beilstein J. Org. Chem. 2014, 10, 1406–1412, doi:10.3762/bjoc.10.144

• with different valency and alkyl spacer lengths by means of Cu(I)-catalysed azide–alkyne cycloadditions. Evaluation of these compounds as α-mannosidase inhibitors led to significant multivalent effects and further demonstrated the decisive influence of scaffold rigidity on binding affinity enhancements

• iminosugars 5 onto polyalkyne “clickable” scaffolds 2–4 by Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reactions [40][41] (Figure 1). N-alkyl derivatives of DNJ were logically chosen as the peripheral ligands because of the therapeutic relevance of these compounds [42]. In addition, most of the

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

• construction of a 1,4-disubstituted-1,2,3-triazole unit via a copper(I)-catalyzed modern version of the Huisgen-type azide–alkyne cycloaddition [6][7][8][9][10] has been considered to be a powerful ligation method for glycoconjugation [11][12][13][14][15][16]. In addition to the simplicity of this reaction and

Human dendritic cell activation induced by a permannosylated dendron containing an antigenic GM₃-lactone mimetic

• Renato Ribeiro-Viana,
• Elena Bonechi,
• Javier Rojo,
• Clara Ballerini,
• Giuseppina Comito,
• Barbara Richichi and
• Cristina Nativi

Beilstein J. Org. Chem. 2014, 10, 1317–1324, doi:10.3762/bjoc.10.133

• functionalized with an alkyne group by a Cu(I) azide–alkyne cycloaddition (CuAAC) reaction. Then, the mimetic 6 with a butyne group at the anomeric position, which is required for the conjugation to the glycodendron 7 (Scheme 1), was also prepared as already reported [33]. The synthesis of the tricyclic spiro

Tandem Cu-catalyzed ketenimine formation and intramolecular nucleophile capture: Synthesis of 1,2-dihydro-2-iminoquinolines from 1-(o-acetamidophenyl)propargyl alcohols

• Gadi Ranjith Kumar,
• Yalla Kiran Kumar,
• Ruchir Kant and
• Maddi Sridhar Reddy

Beilstein J. Org. Chem. 2014, 10, 1255–1260, doi:10.3762/bjoc.10.125

• compounds in moderate to good yields under mild reaction conditions. Keywords: alkyne; azide; cycloaddition; cyclization; quinoline; Introduction The synthesis of N-sulfonylketenimines via CuAAC (copper-catalyzed azide–alkyne cycloaddition) between terminal alkynes and sulfonyl azides has staged for a

Molecular architecture with carbohydrate functionalized β-peptides adopting 3₁₄-helical conformation

• Nitin J. Pawar,
• Navdeep S. Sidhu,
• George M. Sheldrick,
• Dilip D. Dhavale and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2014, 10, 948–955, doi:10.3762/bjoc.10.93

• corresponding lectins. Taillefumier and coworkers link sugar units to β-peptide amino acid side chains by azide–alkyne cycloaddition [20]. Following the concept of highly organized presentation of sugar units on a β-peptide scaffold, we report on simultaneous incorporation of various sugars (glucose, galactose

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

• . These include the well-known copper-catalyzed azide–alkyne cyclization (CuAAC, “click” reaction) between an azido-CD derivative and an alkyne linker [19][22][23][24] [22], or vice versa, the metal catalyzed reactions between propargyl-CDs and aryl dihalides such as the Sonogashira and Glaser–Hay

End-group-functionalized poly(N,N-diethylacrylamide) via free-radical chain transfer polymerization: Influence of sulfur oxidation and cyclodextrin on self-organization and cloud points in water

• Sebastian Reinelt,
• Daniel Steinke and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 680–691, doi:10.3762/bjoc.10.61

• agents [23][24][25] or (b) indirect by polymer analogous modification of existing end-groups. For the post-modification highly efficient reactions are needed to ensure a high degree of functionalization. For this reason, often “click reactions” [26] such as esterifications [27], azide–alkyne [22], thiol

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• ]. Multicomponent reactions towards amide isosteres often involve an Ugi reaction followed by a Click reaction, in which two of the Ugi-inputs either contain an alkyne or an azide moiety. A well-known example of the latter reaction is the Copper(I) catalyzed azide–alkyne cycloaddition (CuAAC) between acetylenes and

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

• -ansamitocin derivative 6, folate-ansamitocin P-3 conjugate 7 and thiol 8. Strategies for introducing linker-based thiol groups to the aromatic moiety of ansamitocin P-3 for accessing tumor targeting conjugates (CuAAC; Cu-mediated azide–alkyne cycloaddition). Mutasynthetic transformation of aminobenzoic acid

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

• between isoquinolinium-2-ylamide 43 and keteneimine 57 [79], silver salt plays the usual role of a π-philic catalyst, whereas ketene imine 57 is generated by a well-known procedure involving a copper(I)-catalyzed azide–alkyne [3 + 2] cycloaddition (CuAAC) giving rise to 5-cuprated triazole intermediate 56

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

• Regina Berg and
• Bernd F. Straub

Beilstein J. Org. Chem. 2013, 9, 2715–2750, doi:10.3762/bjoc.9.308

• Regina Berg Bernd F. Straub Organisch-Chemisches Institut, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany 10.3762/bjoc.9.308 Abstract The copper-catalyzed azide–alkyne cycloaddition (CuAAC) is one of the most broadly applicable and easy-to-handle

• Huisgen’s azide–alkyne cycloaddition (CuAAC reaction). In fact, the catalytic effect of copper ions had first been mentioned by L’Abbé in 1984 [7], but had henceforth been overlooked until Meldal presented a copper(I)-catalyzed solid-phase synthesis of 1,2,3-triazoles. In this procedure, the terminal alkyne

• Boc groups. Meldal et al. reported this reaction in the context of solid-supported peptide synthesis and expressed their hope for the preparation of a library with triazole-containing peptides. The group of Sharpless, on the other hand, presented a copper-catalyzed azide–alkyne cycloaddition under

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

• ), 125.3 (C-1,4,5,8,13,16), 52.9 (C-9,10), 52.1 (CH2); Anal. calcd for C26H20N18, C, 53.42; H, 3.45; found; C, 53.09; H, 3.58. General procedure for the azide–alkyne cycloaddition. Azide 3 (0.10 g, 0.17 mmol), the 2-propyn-1-yl β-D-glycopyranoside (0.84 mmol), copper(II) acetate (15 mg, 0.08 mmol) and

Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

• Felix Wojcik,
• Sinaida Lel,
• Alexander G. O’Brien,
• Peter H. Seeberger and
• Laura Hartmann

Beilstein J. Org. Chem. 2013, 9, 2395–2403, doi:10.3762/bjoc.9.276

• [20]. Carbohydrate conjugation was achieved by copper-catalyzed azide alkyne cycloaddtion (CuAAC) of carbohydrate ligands on alkyne presenting oligomers [21]. As an alternative conjugation approach to CuAAc, a very efficient thiol–ene coupling (TEC) [22][23][24][25] protocol in a continuous flow

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

• 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

• elapsed between the first contact of the ink with the bed and the moment when the blue colour appeared at the column outlet was measured. Examples of 1,2,3-triazoles with various biological activities. Selected bioactive alicyclic β-amino acids. Experimental setup for the CF reactions. 1,3-Dipolar azide

• –alkyne cycloadditions. Gramm-scale CF synthesis of triazole 22 under conditions B. CF synthesis of 1,2,3-triazole-substituted alicyclic β-amino acid derivatives. Copper contents in the triazole products after column chromatographic purification on silica gel. Supporting Information Supporting

End-labeled amino terminated monotelechelic glycopolymers generated by ROMP and Cu(I)-catalyzed azide–alkyne cycloaddition

• Ronald Okoth and
• Amit Basu

Beilstein J. Org. Chem. 2013, 9, 608–612, doi:10.3762/bjoc.9.66

• accomplished by amidation with an azido-amine linker followed by Cu(I)-catalyzed azide–alkyne cycloaddition with propargyl sugars. Subsequent Teoc deprotection and conjugation with pyrenyl isothiocyanates afforded well-defined end-labeled glycopolymers. Keywords: capping agent; carbohydrate; glycan; olefin

• (Teoc) protected primary amine. The Teoc group is tolerant of subsequent polymer-side-functionalization chemistries, such as amidation and azide–alkyne click reactions. The upfield TMS 1H NMR resonances of the Teoc group are a useful signal for assessing the efficiency and success of post-ROMP

• terminus. The molecular data for 7 obtained by MALDI was in agreement with that obtained from GPC and NMR analysis of polymer 6 (see Supporting Information File 1). Due to its high conversion and functional-group tolerance the copper(I)-promoted azide–alkyne click reaction (CuAAC) has become a powerful

Microwave-assisted three-component domino reaction: Synthesis of indolodiazepinotriazoles

• Rajesh K. Arigela,
• Sudhir K. Sharma,
• Brijesh Kumar and
• Bijoy Kundu

Beilstein J. Org. Chem. 2013, 9, 401–405, doi:10.3762/bjoc.9.41

• ; indolodiazepinotriazoles; Introduction The intermolecular Huisgen azide–alkyne 1,3-dipolar cycloaddition reaction [1][2][3][4][5][6] for the synthesis of 1,2,3-triazoles in both aqueous [7][8][9][10] and organic solvents under either metal-catalyzed [11][12][13] or metal-free conditions [14][15][16] has received

• increasing attention in drug discovery processes [17][18]. The ease of reaction in the intermolecular format has been successfully demonstrated by using both organic/inorganic azides as well as alkynes/diynes [19][20][21]. In contrast to its employment in an intermolecular format, intramolecular azide–alkyne

• efforts to the development of a three-component domino strategy for the synthesis of indole-based polyheterocycles by incorporating the intramolecular azide–alkyne 1,3-dipolar cycloaddition reaction as one of the domino steps. Here we propose a strategy where N-1 of 2-alkynylindole [36][37] can be first

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

• 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

• ) functionalized TPX 7b with PEG and oxanorbonadiene group; (g) functionalized TPX 8b with cRGD (copper-free approach). Functionalization of poly(4-methylpent-1-ene) (TPX) 2. Copper-catalyzed and copper-free azide–alkyne “click“ reaction between functionalized TPX membranes 7a or 7b and cRGD peptide 1b or with

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

• fast methods for the decoration of biomimetic molecules with sugars is of fundamental importance. The glycosylation of peptoids and polyamines as examples of such biomimetic molecules is reported here. The method uses Cu-catalyzed azide alkyne cycloaddition to promote the reaction of azidosugars with

• 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

Copper-catalyzed CuAAC/intramolecular C–H arylation sequence: Synthesis of annulated 1,2,3-triazoles

• Rajkumar Jeyachandran,
• Harish Kumar Potukuchi and
• Lutz Ackermann

Beilstein J. Org. Chem. 2012, 8, 1771–1777, doi:10.3762/bjoc.8.202

• -economical syntheses of annulated 1,2,3-triazoles were accomplished through copper-catalyzed intramolecular direct arylations in sustainable one-pot reactions. Thus, catalyzed cascade reactions involving [3 + 2]-azide–alkyne cycloadditions (CuAAC) and C–H bond functionalizations provided direct access to

• for direct arylations of 1,2,3-triazoles. Thus, we showed that intermolecular copper-catalyzed C–H bond functionalizations could be combined with the Huisgen [51] copper(I)-catalyzed [52][53] [3 + 2]-azide–alkyne cycloaddition (CuAAC)[54], while C–H bond arylations of 1,2,3-triazoles were previously

• consisting of copper(I)-catalyzed [3 + 2]-azide–alkyne cycloadditions (CuAAC) and intramolecular C–H bond arylations. Notably, the optimized copper catalyst accelerated two mechanistically distinct transformations, which set the stage for the formation of up to one C–C and three C–N bonds in a chemo- and

Antifreeze glycopeptide diastereomers

• Lilly Nagel,
• Carsten Budke,
• Axel Dreyer,
• Thomas Koop and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 1657–1667, doi:10.3762/bjoc.8.190

• proline replacements [5]. These peptides exhibit less antifreeze activity than monosaccharide-substituted AFGP analogues without proline residues. Peptoid glycoconjugates with carbohydrate moieties attached by CuI catalyzed azide-alkyne cycloaddition (CuAAC) were devoid of antifreeze activity [17

Parallel solid-phase synthesis of diaryltriazoles

• Matthias Wrobel,
• Jeffrey Aubé and
• Burkhard König

Beilstein J. Org. Chem. 2012, 8, 1027–1036, doi:10.3762/bjoc.8.115

• predictability of their potency and selectivity as inhibitors is still limited. We have recently reported the synthesis of triazole-based α-helix mimetics 3 and 4 [16], which are efficiently available through azide–alkyne cycloadditions [17]. We now report the use of this chemistry to prepare libraries of

• example of a more complex alkyne. The azide–alkyne [3 + 2] cycloaddition was catalyzed with copper(II) sulfate pentahydrate and L-ascorbic acid in DMF overnight at room temperature. A solution of EDTA was added to remove the remaining copper cations from the resin. Resin cleavage under acidic conditions