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

Investigation of the action of poly(ADP-ribose)-synthesising enzymes on NAD⁺ analogues

• Sarah Wallrodt,
• Edward L. Simpson and
• Andreas Marx

Beilstein J. Org. Chem. 2017, 13, 495–501, doi:10.3762/bjoc.13.49

• introducing small, terminal alkyne functionalities at common sites of the adenine base. Upon successful incorporation into PAR, these alkynes serve as handles for copper(I) catalysed azide–alkyne click reaction (CuAAC) [22] with fluorescent dyes. Terminal alkynes are the smallest possible reporter group that

• + analogue or a 1:1 mixture. Then, copper(I)-catalysed azide–alkyne click reaction (CuAAC) is performed and mixture is resolved by SDS PAGE. SDS PAGE analysis of ADP-ribosylation of histone H1.2 with ARTD1, ARTD2, ARTD5 and ARTD6 using NAD+ analogue 1. Upper panel shows Coomassie Blue staining; lower panel

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

Versatile synthesis of end-reactive polyrotaxanes applicable to fabrication of supramolecular biomaterials

• Atsushi Tamura,
• Asato Tonegawa,
• Yoshinori Arisaka and
• Nobuhiko Yui

Beilstein J. Org. Chem. 2016, 12, 2883–2892, doi:10.3762/bjoc.12.287

• methods of introducing functional groups at the threading CD moieties of PRXs are used. Among the various chemical modifications, the introduction of azide or alkynyl groups at the threading CDs of the PRX is particularly attractive, because these functional groups undergo efficient azide–alkyne Huisgen

A versatile route to polythiophenes with functional pendant groups using alkyne chemistry

• Xiao Huang,
• Li Yang,
• Rikard Emanuelsson,
• Jonas Bergquist,
• Maria Strømme,
• Martin Sjödin and
• Adolf Gogoll

Beilstein J. Org. Chem. 2016, 12, 2682–2688, doi:10.3762/bjoc.12.265

• of such functionalization using a Sonogashira cross-coupling [26] and an azide–alkyne Huisgen cycloaddition [27]. One of the advantages of the cross-coupling and click chemistry is that it allows for reaction conditions tolerant for nearly all of the above mentioned functional groups. Additionally

Synthesis, dynamic NMR characterization and XRD studies of novel N,N’-substituted piperazines for bioorthogonal labeling

• Constantin Mamat,
• Marc Pretze,
• Matthew Gott and
• Martin Köckerling

Beilstein J. Org. Chem. 2016, 12, 2478–2489, doi:10.3762/bjoc.12.242

• connection to the label (e.g., fluorescence dye, radionuclide) and the second is used for the introduction of a (bioorthogonal) functional group (e.g., azide, alkyne, phosphane, tetrazine) to later connect to the biomolecule via bioorthogonal ligation. Our aim was the development of novel, N,N

• to demonstrate the Cu-catalyzed azide–alkyne click reaction (Huisgen 1,3-dipolar cycloaddition) and the traceless Staudinger ligation, a proof of concept study was performed for the site-selective labeling of a pharmacologically active peptide and a small organic compound. These compounds provide the

Construction of bis-, tris- and tetrahydrazones by addition of azoalkenes to amines and ammonia

• Artem N. Semakin,
• Aleksandr O. Kokuev,
• Yulia V. Nelyubina,
• Alexey Yu. Sukhorukov,
• Petr A. Zhmurov,
• Sema L. Ioffe and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2016, 12, 2471–2477, doi:10.3762/bjoc.12.241

• 1 to ammonia (Table 2) have a special significance because the expected trishydrazones 11 are obvious analogs of tris(iminomethyl)amines widely used in the catalysis of azide–alkyne cycloadditions [29][30][31][32][34]. Furthermore, intramolecular cyclotrimerization of C=N bonds in trishydrozones

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

• 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

• -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

• [1][2][3]. In 2002, the research groups of Meldal and Sharpless independently discovered the strongly rate-enhancing effect of copper(I) salts for azide–alkyne cycloadditions. The 1,4-disubstituted 1,2,3-triazoles are formed exclusively with essentially quantitative conversion and under mild reaction

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

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• azide–alkyne cycloadditions and various A3-coupling reactions are useful procedures in heterocyclic chemistry. However, several methods based on these protocols have also been developed for the synthesis of heterocyclic phosphonates. The 1,2-dihydroisoquinolin-1-ylphosphonates 172 were formed through a

Bi- and trinuclear copper(I) complexes of 1,2,3-triazole-tethered NHC ligands: synthesis, structure, and catalytic properties

• Shaojin Gu,
• Jiehao Du,
• Jingjing Huang,
• Huan Xia,
• Ling Yang,
• Weilin Xu and
• Chunxin Lu

Beilstein J. Org. Chem. 2016, 12, 863–873, doi:10.3762/bjoc.12.85

• imidazolium backbone and N substituents. The copper–NHC complexes tested are highly active for the Cu-catalyzed azide–alkyne cycloaddition (CuAAC) reaction in an air atmosphere at room temperature in a CH3CN solution. Complex 4 is the most efficient catalyst among these polynuclear complexes in an air

• Inspired by the catalytic activity of Cu(I) species supported by NHC ligand in Cu-catalyzed azide–alkyne cycloaddition (CuAAC) reaction under mild conditions, copper complexes 2–6 were investigated in the CuAAC reaction of azide and phenylacetylene. Firstly, we compared the catalytic activity of different

Creating molecular macrocycles for anion recognition

• Amar H. Flood

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

• house is just as satisfying as that of a new molecule and often takes the same amount of time (left: Franck Boston copyright 123RF.com). Timeline of anion-binding macrocycles. Click chemistry’s copper-catalyzed azide–alkyne cycloaddition (CuAAC) forms 1,2,3-triazoles that stabilize anions by CH hydrogen

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• is the Cu(0)-catalysed azide–alkyne cycloaddition (CuAAC) that can be further enhanced by simultaneous US/MW irradiation [18]. The formation of triazole-substituted CDs has been investigated by US irradiation and products can be synthesized in 2–4 hours (Scheme 2) [19]. Scondo et al. have reported a

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• a cooper(I)-catalyzed azide–alkyne cycloaddition between the 2’-azido-β-CD 31 and the alkyne derivatives 22a,b to access the corresponding monosubstituted CD 32a,b [76]. Synthesis of 3-monosubstituted β-CD derivatives: As the facial position of the reactive groups might modify the catalytic

• partially-protected 2,6-dimethyl-β-CD (Scheme 7) [88]. Finally, CDs bearing an oxime (36 and 39a) or a hydroxamic acid (39b) group in position 3 were prepared as previously described via an azide–alkyne cycloaddition (Scheme 7) [76][80]. Synthesis of difunctionalized β-CD derivatives: As the hydrolytic

• disulfonylimidazole 42 to access a key intermediate easily converted to the corresponding di-2,3-mannoepoxido compound 43 (Scheme 8) [89]. The 3A,3B-diazido-3A,3B-dideoxy-bis(altro)-β-cyclodextrin 44 was then obtained by reaction of 43 with sodium azide and a copper(I)-catalyzed azide–alkyne cycloaddition finally

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

• 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

• multimerization of compound ent-1 with the aim of studying its inhibitory activity when the molecule decorates a multivalent scaffold. Herein we report the synthesis of a tetra- and a nonavalent polyhydroxypiperidine iminosugar, by exploiting the CuI-catalyzed azide-alkyne cycloadditions (CuAAC) [29][30][31][32

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

• investigated and recognized as an epoch-making progress in organic synthesis and green chemistry [11][12][13][14][15]. After many years of research, it was proven that the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC reaction) could be performed under various conditions according to the need of click

• - and para-ethynylaniline, where both of the substrates worked well and the desired bistriazoles 34 could be obtained by a simple trituration and filtration procedure in good yield. The strain-promoted azide-alkyne cycloaddition (SPAAC) reaction could be well-performed without a Cu(І) catalyst. Such

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

• -like macrocycle on the other side, have been easily linked by microwave azide–alkyne 1,3-dipolar cycloaddition. The preliminary relaxivity study of these heterobimetallic complexes was also investigated for potential MRI applications. Results and Discussion We first wish to report a “library” of azido

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• corresponding to the exact molecular weight of each derivative supported these azide–alkyne cycloadditions. The second set of cholesterol conjugates (Scheme 2 and Scheme 3) was prepared by CuAAC of (3β)-3-(prop-2-yn-1-yloxy)cholest-5-ene (10) with azidoalcanols 9a,b [24] and 3β-azidocholest-5-ene (3). These