Synthesis of aromatic glycoconjugates. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger and
• Thomas Ziegler

Beilstein J. Org. Chem. 2014, 10, 2453–2460, doi:10.3762/bjoc.10.256

• hydrogenation of the latter with Lindlar catalyst afforded 7 almost quantitatively. Likewise, copper(I)-catalyzed 1,3-dipolar cycloaddition (Click reaction) [15][16][17][18] of 5 with Fmoc-protected propargylamine afforded first t-butyl benzoate 8 in 87% yield. Hydrogenation of the latter with Pd on charcoal

Solution phase synthesis of short oligoribonucleotides on a precipitative tetrapodal support

• Alejandro Gimenez Molina,
• Amit M. Jabgunde,
• Pasi Virta and
• Harri Lönnberg

Beilstein J. Org. Chem. 2014, 10, 2279–2285, doi:10.3762/bjoc.10.237

• support by a Cu(I) catalyzed click reaction and conventional phosphoramidite chemistry is then applied. The advantage of this support is that the small molecular reagents and byproducts are removed in each coupling cycle by two fully quantitative precipitations from MeOH, one after oxidation and the

Convergent synthetic methodology for the construction of self-adjuvanting lipopeptide vaccines using a novel carbohydrate scaffold

• Vincent Fagan,
• Istvan Toth and
• Pavla Simerska

Beilstein J. Org. Chem. 2014, 10, 1741–1748, doi:10.3762/bjoc.10.181

• ‘click’ reaction [20] was employed to couple multiple copies of purified B cell peptide antigens onto the carbohydrate core and lipidic adjuvanting moiety. This type of convergent approach has a number of advantages over the previously described divergent route. Since each component is synthesized

• building block 1 reported here is concise and efficient, involving only one chromatographic step and takes advantage of the highly efficient “click” reaction. Synthesis of lipo-amino acid Lipidation of peptides is important as it is often used to improve stability and permeability of potential therapeutics

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

• and pyridine 7:3 as previously described for compound 8. The CuAAC “click” reaction was carried out as previously described for the galacto-clusters 9 and 13 and afforded the cone calix[4]arene 16 (Scheme 3) and 1,3-alternate calix[4]arene 19 (Scheme 4) in 46% isolated yield. Microwave irradiation

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

• 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

• -products together with a better assessment of complete surface group modifications. Hence, known 14 [36] was first cycloadded to mannosylazide 3 under the above CuAAc conditions. The “click reaction” proceeded exceptionally efficiently and provided bromoacylated dendron precursor 18 in 94% yield

• 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

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

• increase solubility [8], prolong the in vivo action [9] or for targeting drug delivery [10] has been described. The potent anti-inflammatory drug dexamethasone was coupled to a multifunctional PEG, prepared by a click reaction, for treatment of rheumatoid arthritis [11]. A heterobifunctional PEG has been

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

• context cyclopeptoids 2–4 appear as ideal building blocks because of their simplicity of synthesis and easy functionalization by click reaction (Figure 1). In the present paper, we report the synthesis of the first examples of cyclopeptoid-based iminosugar clusters. The influence of valency, size, linker

A complete series of 6-deoxy-monosubstituted tetraalkylammonium derivatives of α-, β-, and γ-cyclodextrin with 1, 2, and 3 permanent positive charges

• Martin Popr,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2014, 10, 1390–1396, doi:10.3762/bjoc.10.142

• Huisgen 1,3-dipolar cycloaddition [30] (most popular ‘click reaction’) or the reduction to the amine. Our strategy involved the synthesis of the alkylation agent 1-azido-2-iodoethane (24) (Scheme 5) which would be used for the quaternization of the tertiary amine intermediate. The reaction sequence for

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

• 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

Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

• Melanie Rauschenberg,
• Eva-Corrina Fritz,
• Christian Schulz,
• Tobias Kaufmann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 1354–1364, doi:10.3762/bjoc.10.138

• -terminated SAMs [33], by Diels–Alder reaction of cyclopentadienes and furans on maleimide-terminated SAMs [34], by thiol–ene click reaction of functionalized thiols on alkene-terminated SAMs [35] as well as by strain promoted cycloadditions on azide- and nitriloxide-terminated SAMs [36] using μCP. Homogenous

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

• the key reaction step. The copper-catalyzed regioselective click reaction was tremendously accelerated with assistance of microwave irradiation. Keywords: click conjugations; copper-catalyzed; microwave irradiation; multivalent glycosystems; neoglycoconjugates; one-pot; Introduction Oligosaccharides

• ]. Moreover, the inertness of both azide and alkyne groups towards a majority of functional groups connected to the core of a variety of biomolecules also renders the click reaction particularly suitable for covalently linking bioactive molecular entities [21][22]. For example, the click strategy is

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• obtain the desired polypeptide. The condensation can occur via chemoselective ligation techniques such as native chemical ligation (NCL), expressed protein ligation (EPL), Staudinger ligation or click reaction [8][79]. Recently, peptide drugs as the pharmaceuticals Enfuvirtide, Eptifibitide and

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

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

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

• centrifugation and purified in water by repeated redispersion/centrifugation cycles. It was characterized by FTIR (Figure 1c) and solution-phase 1H NMR (Figure 2c). ND-PG-BPP The click reaction of ND-PG-N3 and G*BPP was conducted in a similar manner to our reported procedure [22]. G*BPP (8.0 mg) was added to a

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

• -isomer over the 1,5-isomer [85]. In 2010, Nenajdenko et al. described an Ugi/Click-approach using chiral isocyanoazides, which in turn were derived from L-amino alcohols [85]. The Ugi-products were obtained in good yields, with high diastereoselectivity (de >99%). A follow-up Click reaction using 10 mol

• and anticancer activities [88]. The Ugi reaction provided the azide moieties 84a or 84b, whereas a reaction between sodium acetylide and imines of general structure 86 afforded the alkyne derivatives [89][90]. A subsequent Click reaction gave the final triazole-mimics (88a or 88b) in good to excellent

Synthesis and biological activity of N-substituted-tetrahydro-γ-carbolines containing peptide residues

• Nadezhda V. Sokolova,
• Valentine G. Nenajdenko,
• Vladimir B. Sokolov,
• Daria V. Vinogradova,
• Elena F. Shevtsova,
• Ludmila G. Dubova and
• Sergey O. Bachurin

Beilstein J. Org. Chem. 2014, 10, 155–162, doi:10.3762/bjoc.10.13

• )-catalyzed click chemistry – one of the most effective conjugation methods [21][22]. Thus, heating the educts with Cu(II)/sodium ascorbate in a biphasic mixture of CH2Cl2/H2O during 1 h provided compounds 6a–g (Scheme 3). According to the 13C NMR spectra, the click reaction proceeds regioselective in all

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

• by CuI and Na2CO3 was substituted by NEt3 [24], but the work-up of the reaction appeared difficult, and no final product of the click reaction was obtained. Finally, we decided to adopt the synthetic conditions shown in Scheme 2 [25][26]. The triptycene derivative 3 was reacted with the unsaturated

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

• click reaction of 3-butyn-1-ylidynetrisphosphonate 15 with benzyl azide, which results in novel triazole compound 35 bearing the trisphosphonate function (Scheme 17) [26]. In contrast to methylenebisphosphonate esters, methylidynetrisphosphonate esters have a tendency to undergo dephosphonylation when

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

• of a fluorescent cyclodextrin via click reaction. The changes in the spectroscopic properties of the fluorescent cycloadduct were investigated in the presence and absence of the competitive guest potassium adamantane-1-carboxylate. The intermolecular formation of polymeric structures with elongated

Synthesis and structure of trans-bis(1,4-dimesityl-3-methyl-1,2,3-triazol-5-ylidene)palladium(II) dichloride and diacetate. Suzuki–Miyaura coupling of polybromoarenes with high catalytic turnover efficiencies

• Jeelani Basha Shaik,
• Venkatachalam Ramkumar,
• Babu Varghese and
• Sethuraman Sankararaman

Beilstein J. Org. Chem. 2013, 9, 698–704, doi:10.3762/bjoc.9.79

• electronics applications. Experimental 1,4-Dimesityl-3-methyl-1,2,3-triazolium iodide was prepared from the corresponding triazole, which in turn was prepared by the click reaction of mesitylacetylene and mesitylazide according to the literature [27]. Complex 1 was synthesized in a similar manner as reported

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

• 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

• post-polymerization modification reaction. Post-polymerization modification of macromolecules by click reaction can be accomplished in two ways; (i) a macromolecule bearing alkyne groups is reacted with an azido-monomer or (ii) a macromolecule bearing azide groups is reacted with a monomer bearing a

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

• ) F 1s core level, (c) N 1s core level. UV spectra of TPX 8c and 8d functionalized with fluorescein revealing the efficiency of the 1,3-dipolar cycloaddition reactions on modified TPX membranes. Continuous line: 8d; dotted line: 8c; dashed line: substrate for Huisgen-type “click” reaction 7a. Cell

• ) 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

• synthesize also 1,3,4,6-tetra-O-acetyl-N-azidoacetyl-D-galactosamine (Ac4GalNAz = 2) and 1,3,4,6-tetra-O-acetyl-N-azidoacetyl-D-mannosamine (Ac4ManNAz = 3) with similar yields under these optimized conditions (see Supporting Information File 1). Click reaction on alkynylated polyamines and peptoids The