A switchable [2]rotaxane with two active alkenyl groups

• Xiu-Li Zheng,
• Rong-Rong Tao,
• Rui-Rui Gu,
• Wen-Zhi Wang and
• Da-Hui Qu

Beilstein J. Org. Chem. 2018, 14, 2074–2081, doi:10.3762/bjoc.14.181

• +) containing intermediate compound 5 were assembled in dichloromethane through host–guest interaction and capped with compound 8 under Cu(I)-catalyzed azide–alkyne cycloaddition to get the final [2]rotaxane with two distinguishable recognition sites. The target [2]rotaxane R1 was then characterized by 1H NMR

Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

• Vladimir A. Burilov,
• Guzaliya A. Fatikhova,
• Mariya N. Dokuchaeva,
• Ramil I. Nugmanov,
• Diana A. Mironova,
• Pavel V. Dorovatovskii,
• Victor N. Khrustalev,
• Svetlana E. Solovieva and
• Igor S. Antipin

Beilstein J. Org. Chem. 2018, 14, 1980–1993, doi:10.3762/bjoc.14.173

• /bjoc.14.173 Abstract The synthesis of new calix[4]arenes adopting a cone stereoisomeric form bearing two or four azide fragments on the upper rim and water-soluble triazolyl amphiphilic receptors with two or four polyammonium headgroups via copper-catalyzed azide–alkyne cycloaddition reaction has been

• solutions. Results and Discussion Synthesis of polyammonium calix[4]arene derivatives The functionalization of calix[4]arenes with azide groups paves the way to introduce a wide variety of functional groups [27] on the upper rim of the macrocycle by, e.g., the copper-catalyzed azide–alkyne cycloaddition

Efficient catenane synthesis by cucurbit[6]uril-mediated azide–alkyne cycloaddition

• Antony Wing Hung Ng,
• Chi-Chung Yee,
• Kai Wang and
• Ho Yu Au-Yeung

Beilstein J. Org. Chem. 2018, 14, 1846–1853, doi:10.3762/bjoc.14.158

• other recognition units render them promising building blocks for the construction of other high-order interlocked structures. Keywords: azide–alkyne cycloaddition; catenane; click chemistry; cucurbit[6]uril; mechanical bond; Introduction Catenanes are topologically non-trivial molecules possessing

• a preliminary study of a [6]catenane synthesis featuring the CB[6]-mediated azide–alkyne cycloaddition (CBAAC) using phenanthroline-based building blocks [24]. To further explore the applicability and generality of the CBAAC in the construction of mechanically interlocked molecules, we report here

• ] binding to the ammoniums on the building blocks to improve the efficiency of CBAAC [23]. In view of the low solubility of CB[6] and the possibility of thermal-assisted azide–alkyne cycloaddition of the unbound building blocks that may lead to the incomplete cycloaddition and other side products, we

Synthesis and photophysical studies of a multivalent photoreactive Ru^II-calix[4]arene complex bearing RGD-containing cyclopentapeptides

• Sofia Kajouj,
• Lionel Marcelis,
• Alice Mattiuzzi,
• Adrien Grassin,
• Damien Dufour,
• Pierre Van Antwerpen,
• Didier Boturyn,
• Eric Defrancq,
• Mathieu Surin,
• Julien De Winter,
• Pascal Gerbaux,
• Ivan Jabin and
• Cécile Moucheron

Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150

• anchoring i) of the photoreactive [Ru(TAP)2phen]2+ complex on the calix[4]arene small rim through a peptide-type coupling and ii) of the four c-[RGDfK] moieties on the opposite rim through a copper-catalyzed azide–alkyne cycloaddition (CuAAC) [66][67][68] (Figure 1). It was thus necessary to block the calix

• + CF3COO−]+ by comparison between the experimental and theoretical isotope distributions (see Supporting Information File 1). With RuII-calix[4]arene complex 7 in hands, we next moved to the introduction of the cellular targeting units on the large rim through copper-catalyzed azide–alkyne cycloaddition

• ), as these nanomaterials are known to catalyze efficiently a wide range of organic reactions and notably the azide–alkyne cycloaddition [79]. Calixarene 7 was reacted with a slight excess (5 equiv) of cyclopeptide 8 in the presence of CuNPs and the mixture was heated by microwave (100 W) at 50 °C for 1

Hyper-reticulated calixarene polymers: a new example of entirely synthetic nanosponge materials

• Alberto Spinella,
• Marco Russo,
• Antonella Di Vincenzo,
• Delia Chillura Martino and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2018, 14, 1498–1507, doi:10.3762/bjoc.14.127

• extend and possibly improve the supramolecular binding abilities of CyNSs, mixed cyclodextrin-calixarene co-polymers nanosponges (CyCaNSs) were recently synthesized by exploiting a classical “click-chemistry” approach, namely the CuAAC reaction (Cu-catalyzed azide–alkyne cycloaddition [28][29][30

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• ; SPSAC) which takes place without any catalyst and at ambient temperature. Such mild reaction conditions, (ultra) fast and unambiguous product formation make SPSAC useful in bio-orthogonal applications and competitive in comparison with analogous strain-promoted azide–alkyne cycloaddition (SPAAC). The

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• and carboxylic acid Boc protection using an improvised attritor-type mill. Nucleobase Boc protection via transient silylation using an improvised attritor-type mill. Chemoselective N-acylation of an aminonucleoside using LAG in a MBM. Azide–alkyne cycloaddition reactions performed in a copper vessel

Sequential Ugi reaction/base-induced ring closing/IAAC protocol toward triazolobenzodiazepine-fused diketopiperazines and hydantoins

• Robby Vroemans,
• Fante Bamba,
• Jonas Winters,
• Joice Thomas,
• Jeroen Jacobs,
• Luc Van Meervelt,
• Jubi John and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 626–633, doi:10.3762/bjoc.14.49

• together all necessary functionalities for further transformations. The Ugi adducts were then subjected to a base-induced ring closing and an intramolecular azide–alkyne cycloaddition reaction in succession to obtain highly fused benzodiazepine frameworks. Keywords: benzodiazepine; 2,5-diketopiperazine

• ; hydantoin; intramolecular azide–alkyne cycloaddition; Ugi reaction; Introduction The versatile bioactivities of multiring-fused heterocyclic scaffolds continue to attract significant attention in developing new methods for their synthesis. A plethora of functionalized fused heterocycles can be easily

• multicomponent reactions with intramolecular azide–alkyne cycloaddition (IAAC) for the generation of triazole-fused heterocycles [12][13][14][15][16][17][18][19][20][21][22][23]. In this report we disclose our results on the development of a sequential synthetic approach involving Ugi 4-component reaction (4-CR

Synthesis and biological evaluation of RGD and isoDGR peptidomimetic-α-amanitin conjugates for tumor-targeting

• Lizeth Bodero,
• Paula López Rivas,
• Barbara Korsak,
• Torsten Hechler,
• Andreas Pahl,
• Christoph Müller,
• Daniela Arosio,
• Luca Pignataro,
• Cesare Gennari and
• Umberto Piarulli

Beilstein J. Org. Chem. 2018, 14, 407–415, doi:10.3762/bjoc.14.29

• disulfide linker in the cytoplasm. In another example, Perrin and co-workers conjugated the N-propargylasparagine of an amanitin analog to a cycloRGD integrin ligand (cyclo[RGDfK]) using a copper-catalyzed azide–alkyne cycloaddition [8]. The conjugates were tested in the U87 glioblastoma cell line, but only

Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles

• Vivek Poonthiyil,
• Thisbe K. Lindhorst,
• Vladimir B. Golovko and
• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2

• modification using strain-promoted azide–alkyne cycloaddition In 2014, Workentin and co-workers used the strain promoted azide–alkyne cycloaddition (SPAAC) [53][54][55][56] to modify AuNP surfaces [57]. Firstly 2.8 nm AuNPs functionalized with strained dibenzocyclooctyne derivatives (DBCO-AuNPs) were

• conflicting reports in the literature with regard to the use of Cu(I)-catalysed azide–alkyne cycloaddition with AuNPs. Indeed although several groups have reported the successful use of CuAAC for the modification of AuNPs, both our own investigations, and those of number of other groups, have found that AuNP

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• ) followed by treatment with aqueous ammonia (rt, 3 h). Click chemistry for the preparation of capped RNA and cap analogues. (A) Preparation of capped RNA via a copper-catalyzed azide–alkyne cycloaddition (CuAAC) of an azido-modified cap analogue with a 5'-alkyne bearing RNA [120]. (B) An alkyne-modified

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• intriguing versatility as building blocks in organic and medicinal chemistry, as their reactivity is unique. Their chemistry involves several highly selective reactions, e.g., [3 + 2] cycloadditions with azides and isoelectronic functional groups (among them the copper or ruthenium-catalyzed azide–alkyne

• cycloaddition, CuAAC and RuAAC), the thiol–yne reaction, Diels–Alder reactions and the Sonogashira cross-coupling. While amino acids with a terminal alkyne in the side chain are well-known, the synthesis of their correlates where the carboxy group is replaced by a terminal alkyne is still tedious. Nevertheless

Solvent-free copper-catalyzed click chemistry for the synthesis of N-heterocyclic hybrids based on quinoline and 1,2,3-triazole

• Martina Tireli,
• Silvija Maračić,
• Stipe Lukin,
• Marina Juribašić Kulcsár,
• Dijana Žilić,
• Mario Cetina,
• Ivan Halasz,
• Silvana Raić-Malić and
• Krunoslav Užarević

Beilstein J. Org. Chem. 2017, 13, 2352–2363, doi:10.3762/bjoc.13.232

• spin resonance (ESR) spectroscopy; in situ Raman monitoring; mechanochemistry; quinoline; solid-state click chemistry; Introduction The copper-catalyzed azide–alkyne cycloaddition (CuAAC) represents a prime example of click chemistry. Click chemistry describes “a set of near-perfect” reactions [1] for

• it increases reaction rates and yields and directs the azide–alkyne cycloaddition exclusively towards 1,4-substituted regioisomers, whereas the non-catalyzed process results in a non-stoichiometric mixture of 1,4- and 1,5-regioisomers. Even though CuAAC reactions are efficiently performed in solution

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

An eco-compatible strategy for the diversity-oriented synthesis of macrocycles exploiting carbohydrate-derived building blocks

• Sushil K. Maurya and
• Rohit Rana

Beilstein J. Org. Chem. 2017, 13, 1106–1118, doi:10.3762/bjoc.13.110

• the iterative use of readily available sugar-derived alkyne/azide–alkene building blocks coupled through copper catalyzed azide–alkyne cycloaddition (CuAAC) reaction followed by pairing of the linear cyclo-adduct using greener reaction conditions. The eco-compatibility, mild reaction conditions

• the synthesis. The cyclization of the linear precursor is usually achieved by utilizing various ring-closing reactions such as Diels–Alder reactions, [15] aldol reactions, [16] copper-catalyzed azide–alkyne cycloaddition, [17][18] macrolactonization, macrolactamizations, Staudinger ligation or

• ] glycosides and macrocyclic glycolipids [11]. Similarly, the copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction has found wide application in medicinal chemistry [33], biology [34][35], polymer chemistry [36], carbohydrates [37][38][39][40], peptides [41][42][43][44] and in materials science [45][46

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• peanut agglutinin [25]. In this case, the glycosyl residue is not coated on the gold surface by means of a thiol moiety but exploiting the strain-promoted azide–alkyne cycloaddition (SPAAC) to covalently link an azido galactoside on a lipid cyclooctyne. In this manner, the amphiphilic glyco-lipid can be

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• the multistep synthesis of rufinamide, an antiepileptic agent [14] (Scheme 3). The process involves three steps namely azide synthesis, amide synthesis and click reaction or azide–alkyne cycloaddition. For the azide synthesis, the aryl bromide (1 equiv) and sodium azide (1.3 equiv) are reacted in a

Interactions between shape-persistent macromolecules as probed by AFM

• Johanna Blass,
• Jessica Brunke,
• Franziska Emmerich,
• Cédric Przybylski,
• Vasil M. Garamus,
• Artem Feoktystov,
• Roland Bennewitz,
• Gerhard Wenz and
• Marcel Albrecht

Beilstein J. Org. Chem. 2017, 13, 938–951, doi:10.3762/bjoc.13.95

• , synthesized from polymer 8 (Scheme 3) through Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) with the triethylene glycol linker 11 (N3-TEG-NH2) which had been prepared in a five-step procedure [62][63]. Probing multivalent interactions by AFM The adhesive forces of 12, due to supramolecular interactions

Energy down converting organic fluorophore functionalized mesoporous silica hybrids for monolith-coated light emitting diodes

• Markus Börgardts and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2017, 13, 768–778, doi:10.3762/bjoc.13.76

• functionalization can be achieved upon ligating a triethylsiloxy-functionalized azide and a terminal alkynyl-functionalized luminophore by CuAAC (Cu-catalyzed azide–alkyne cycloaddition) [21][22][23]. Commencing from a 2-hydroxy-substituted Nile red 1 or 3-hydroxymethylperylene (2) the alkyne-substituted

Fast and efficient synthesis of microporous polymer nanomembranes via light-induced click reaction

• Qi An,
• Youssef Hassan,
• Xiaotong Yan,
• Peter Krolla-Sidenstein,
• Tawheed Mohammed,
• Mathias Lang,
• Stefan Bräse and
• Manuel Tsotsalas

Beilstein J. Org. Chem. 2017, 13, 558–563, doi:10.3762/bjoc.13.54

• solid liquid interfacial layer-by-layer (LbL) synthesis of CMP-nanomembranes via Cu catalyzed azide–alkyne cycloaddition (CuAAC). However, this process featured very long reaction times and limited scalability. Herein we present the synthesis of surface grown CMP thin films and nanomembranes via light

• catalyzed azide–alkyne cycloaddition (CuAAC) approach, respectively [16]. These procedures are still limited to conductive substrates or associated with long reaction times. In this work, we present a novel strategy for the LbL synthesis of CMP thin films and nanomembranes, using the light-induced and

Solid-phase enrichment and analysis of electrophilic natural products

• Frank Wesche,
• Yue He and
• Helge B. Bode

Beilstein J. Org. Chem. 2017, 13, 405–409, doi:10.3762/bjoc.13.43

• ). Furthermore, the molecular formula of the cleaved azide–alkyne cycloaddition product 3 was confirmed by HPLC–HRMS (calcd mass: m/z 567.2636 [M + H]+, found: m/z 567.2635 [M + H]+, Δppm = 0.1). Compound 1 could hardly be detected in extracts from standard growth media but was detected from infected insects and

• dinitrogen (−28) as characteristic fragments for CARR adducts. Principle of azidation of XAD extracts from P. luminescens TT01 containing 1 and subsequent azide enrichment with CARR (2). After the vicinal azido alcohol is covalently bound to the resin through an azide–alkyne cycloaddition, compound 3 is

• tested strains, calculated molecular formulas of possible azide–alkyne cycloaddition products, and the molecular formulas of the putative parent compounds derived from subtraction of the azide and CARR-derived moiety (C13H19N4O2S). Supporting Information Supporting Information File 30: Materials

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

• Michal Medvecký,
• Igor Linder,
• Luise Schefzig,
• Hans-Ulrich Reissig and
• Reinhold Zimmer

Beilstein J. Org. Chem. 2016, 12, 2898–2905, doi:10.3762/bjoc.12.289

• -oxazines bearing the newly installed alkynyl group at C-5 are ideal candidates for efficient subsequent transformations. A very popular and widely applied reaction of terminal alkynes is the copper-catalyzed azide–alkyne cycloaddition, also termed as click reaction, efficiently leading to 1,4-disubstituted

Dinuclear thiazolylidene copper complex as highly active catalyst for azid–alkyne cycloadditions

• Anne L. Schöffler,
• Ata Makarem,
• Frank Rominger and
• Bernd F. Straub

Beilstein J. Org. Chem. 2016, 12, 1566–1572, doi:10.3762/bjoc.12.151

• -heterocyclic carbene, linker, sacrificial ligand, and counter ion. Keywords: catalysis; click; copper; CuAAC; N-heterocyclic carbene; thiazole; Introduction The copper-catalyzed azide–alkyne cycloaddition (CuAAC) is one of the most important “click” reactions for the facile covalent linking of two molecules

• Anne L. Schoffler Ata Makarem Frank Rominger Bernd F. Straub Organisch-Chemisches Institut, Universität Heidelberg, Im Neuenheimer Feld 270, D-69120 Heidelberg, Germany 10.3762/bjoc.12.151 Abstract A dinuclear N-heterocyclic carbene (NHC) copper complex efficiently catalyzes azide–alkyne

• cycloaddition (CuAAC) “click” reactions. The ancillary ligand comprises two 4,5-dimethyl-1,3-thiazol-2-ylidene units and an ethylene linker. The three-step preparation of the complex from commercially available starting compounds is more straightforward and cost-efficient than that of the previously described

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• and Instability of Genomes, Sorbonne Universités, Muséum National d'Histoire Naturelle, INSERM U 1154, CNRS UMR 7196, 57 rue Cuvier, C.P. 26, 75231 Paris cedex 05, France 10.3762/bjoc.12.128 Abstract Efficient protocols based on Cu(I)-catalyzed azide–alkyne cycloaddition were developed for the

• helices by TFO-MGB conjugates was evaluated by gel-shift experiments. The presence of MGB in these conjugates did not affect the binding parameters (affinity and triplex stability) of the parent TFOs. Keywords: binding affinity; click chemistry; Cu(I)-catalyzed azide–alkyne cycloaddition; pyrrole

• experience, these reactions are not suitable for TINA-TFO derivatives due to excessive formation of side products. Copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) as a variation of the Huisgen 1,3-dipolar cycloaddition has become a widely used conjugation method in which the stereoselective formation

Copper-catalyzed [3 + 2] cycloaddition of (phenylethynyl)di-p-tolylstibane with organic azides

• Mizuki Yamada,
• Mio Matsumura,
• Yuki Uchida,
• Masatoshi Kawahata,
• Yuki Murata,
• Naoki Kakusawa,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2016, 12, 1309–1313, doi:10.3762/bjoc.12.123

• : cycloaddition; copper catalyst; ethynylstibane; organic azide; 1,2,3-triazole; Introduction The 1,3-dipolar azide–alkyne cycloaddition (AAC) has been effective for the synthesis of a wide variety of 1,2,3-triazoles [1]. However, this reaction has some limitations such as the requirement of high temperature and

• 3a with NOBF4 afforded pentavalent organoantimony compound 6 in 85% yield. It is noteworthy that 5-bismuthanotriazole was demetallated upon reaction with NOBF4 to give the corresponding 5-nitroso compound [24]. Conclusion In conclusion, the Cu-catalyzed azide–alkyne cycloaddition of (phenylethynyl)di