Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• , a novel competition assay employing ‘clickable’ active-site-labelling probes was developed. These compounds contain terminal alkyne moieties, which can be exploited for straightforward decoration via copper(I)-catalyzed alkyne–azide cycloaddition (CuAAC), the prototypic click reaction. This

Nucleoside macrocycles formed by intramolecular click reaction: efficient cyclization of pyrimidine nucleosides decorated with 5'-azido residues and 5-octadiynyl side chains

• Jiang Liu,
• Peter Leonard,
• Sebastian L. Müller,
• Constantin Daniliuc and
• Frank Seela

Beilstein J. Org. Chem. 2018, 14, 2404–2410, doi:10.3762/bjoc.14.217

• Organische Chemie, Universität Münster, Corrensstrasse 40, 48149 Münster, Germany 10.3762/bjoc.14.217 Abstract Copper(I)-promoted "click" cyclization in the presence of TBTA afforded nucleoside macrocycles in very high yields (≈70%) without using protecting groups. To this end, dU and dC derivatives

• and 1H,1H-NMR coupling constants. The sugar conformation (N vs S) was different in solution as compared to the solid state. Keywords: click cyclization; conformation; macrocycles; nucleosides; X-ray; Introduction The field of macrocycles was initiated by the work of Ruzicka and his structure

• and deprotection steps are necessary to control the cyclization process. Preorganization of the molecules can help to make cyclization more efficient. Azide–alkyne "click" chemistry has been executed to generate cyclic peptides [11][12][13], cyclic oligonucleotides [14][15][16][17] and other

Catalyst-free synthesis of 4-acyl-NH-1,2,3-triazoles by water-mediated cycloaddition reactions of enaminones and tosyl azide

• Lu Yang,
• Yuwei Wu,
• Yiming Yang,
• Chengping Wen and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2018, 14, 2348–2353, doi:10.3762/bjoc.14.210

• numerous organic compounds [24][25][26][27][28]. The amazingly rapid and broad permeation of 1,2,3-triazoles to multidisciplinary areas can majorly be attributed to the occurrence of robust synthetic methods toward this heterocycle. The copper-catalyzed click [3 + 2] cycloaddition of azides and alkynes [29

Tetrathiafulvalene – a redox-switchable building block to control motion in mechanically interlocked molecules

• Hendrik V. Schröder and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2018, 14, 2163–2185, doi:10.3762/bjoc.14.190

• (6) ring threaded onto a water-soluble axle [80]. The rotaxane was synthesized in 23% yield by a template/capping strategy where one stopper is attached using copper-catalyzed azide–alkyne click chemistry after the formation of the precursor pseudorotaxane. Due to the hydrophobic effect, the neutral

• = 6,300 M−1) which is embedded in an axle molecule with two azide residues. The second station, the dihydroxynaphthalene moiety (green), displays a lower association constant of Ka = 5,800 M−1. The pseudorotaxane precursor was end-capped by a double copper-catalyzed azide–alkyne click reaction in CH2Cl2

• in 2008 (Figure 20) [97]. The tripodal [4]rotaxane 22, consisting of a trivalent axle, in which each arm is encircled by a host molecule 3, was synthesized by a copper-catalyzed click protocol in 40% yield. A combination of electrochemical and spectroscopic methods was used to investigate a potential

Revisiting ring-degenerate rearrangements of 1-substituted-4-imino-1,2,3-triazoles

• James T. Fletcher,
• Matthew D. Hanson,
• Joseph A. Christensen and
• Eric M. Villa

Beilstein J. Org. Chem. 2018, 14, 2098–2105, doi:10.3762/bjoc.14.184

• recent years [1][2][3][4][5][6][7], enabled by efficient preparation from the Sharpless–Meldal copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction [8][9][10][11]. Click chelators with a variety of N-donor units connected at the 4-triazolyl position have been reported, including pyridine [12][13

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

• amide reaction between compound 6 and 6-azidohexan-1-amine in the presence of 2-chloro-4,6-dimethoxy-1,3,5-triazine and N-methylmorpholine. Finally, the classical and effective “Click” reaction was used to produce the target compound [2]rotaxane R1. The crown ether 9 and dibenzylammonium ion (R2NH2

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

• high affinity to ATP [26]. Herein we report the synthesis of new amphiphilic water-soluble calix[4]arene derivatives with cone conformation containing two or four polyammonium groups on the upper rim by using a click chemistry approach and the results of binding studies toward nucleotides in aqueous

An amphiphilic pseudo[1]catenane: neutral guest-induced clouding point change

• Tomoki Ogoshi,
• Tomohiro Akutsu and
• Tada-aki Yamagishi

Beilstein J. Org. Chem. 2018, 14, 1937–1943, doi:10.3762/bjoc.14.167

• (CuAAC) ‘‘click’’ reaction (see details in the experimental section). In addition, model compound 4 was also synthesized as a reference (Figure 1d). Compound 3 is soluble in various organic and aqueous solvents as it comprises eight amphiphilic tri(ethylene oxide) chains. We investigated the

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

Design, synthesis and structure of novel G-2 melamine-based dendrimers incorporating 4-(n-octyloxy)aniline as a peripheral unit

• Cristina Morar,
• Pedro Lameiras,
• Attila Bende,
• Gabriel Katona,
• Emese Gál and
• Mircea Darabantu

Beilstein J. Org. Chem. 2018, 14, 1704–1722, doi:10.3762/bjoc.14.145

• -triazine dendrimers exhibiting mesogenic behaviour. The first cases known so far refer to N-substituted G-0-3 dendritic melamines [19][20][21] with n-octyl peripheral groups as unconventional columnar liquid crystals and G-0 tris(triazolyl)triazines (available via the “click” reaction between 2,4,6-tris

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• -radical mediated “click” process with diverse applications in small molecule and polymer synthesis and has been reviewed [74][75][76]. The importance of the thiol-ene reaction in the synthesis of β-hydroxy sulfides is exemplified by the work of Scanlan and co-workers as shown in Scheme 41 [77][78

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

• report on the synthesis and characterization (FTIR, solid-state NMR, SEM) of a new class of entirely synthetic nanosponge materials based on calixarenes (CaNSs), by reacting a tetrakis(propargyloxy)calix[4]arene with alkyl diazides. The synthesis was accomplished by means of a classical “click” approach

[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

• reaction conditions together with very high and reverse regioselectivity and efficiency (in most cases 85–99% yields) makes the CuSAC reaction a very good alternative to the well-established azide–alkyne click-reaction [117] useful not only in classical organic synthesis but also in bioconjugation

• reaction conditions (aqueous t-BuOH solution at 60 °C) and can be considered as a good illustration of the click-reaction. Another important example of sydnone cycloaddition involves a very fast reaction with strained seven- or eight-membered cycloalkynes (strain-promoted sydnone alkyne cycloaddition

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• betulinic acid analogs were synthesized by using azide–alkyne click reaction and their anticancer activities against different cancer cell lines and normal human PBMC cell line were evaluated by MTT assay. Conjugate 42 was found to be extremely potent against HT-29 cell line with an IC50 value of 14.9 μM

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

• (Scheme 5) [42]. In the absence of light, azobenzene derivatives were isolated as the pure E-isomers. In their original report, Sharpless and co-workers described the use of copper turnings to promote a regioselective azide–alkyne [3 + 2]-cycloaddition ("click") reaction over 24 hours [43]. High-speed

• ball milling using a custom-made copper vial and copper ball enabled efficient reaction between propyne-derivatised photoswitches and an azidodeoxynucleoside click partner (Scheme 6) [44]. In contrast to the solution-phase (Cu(I)-promoted) reactions, no contamination of the ball milled products by

• copper salts was found. In an attempt to expedite the LAG reaction, millimol-scale reactions between the p-azobenzene-appended alkyne and 5′-azido-5′-deoxythymidine were attempted in a more capacious copper vessel with a 15 mm diameter zirconia ball (Figure 3). Clean and complete click reactions were

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• intrinsic functional group for direct conjugation with the peptide/linker (Figure 4) or a functional group able to be derivatized for further conjugation (i.e., click chemistry [86]). In the latter case, the site of derivatization has to be carefully selected so that the biological activity of the drug and

An uracil-linked hydroxyflavone probe for the recognition of ATP

• Márton Bojtár,
• Péter Zoltán Janzsó-Berend,
• Dávid Mester,
• Dóra Hessz,
• Mihály Kállay,
• Miklós Kubinyi and
• István Bitter

Beilstein J. Org. Chem. 2018, 14, 747–755, doi:10.3762/bjoc.14.63

• this probe to include complementary base-pairing interactions. The theoretical calculations revealed the availability of multiple complex structures. The synthesis was performed using click chemistry and the nucleotide recognition properties of the probe were evaluated using fluorescence spectroscopy

• interactions, which prompted us towards the synthesis of UHF by click chemistry. Fluorescence spectroscopy revealed a selective complexation with ATP with an association constant of around 2∙104 M−1 and a ratiometric response in the excitation spectrum. Results and Discussion Structure and calculations Based

• further stabilizes the complex, and this structure is energetically more favorable. These results prompted us towards the synthesis and evaluation of this promising molecule. Synthesis The synthesis of UHF is depicted in Scheme 1. UHF was synthesized by the CuAAC (click) reaction of 7-propargyloxy-3

Continuous multistep synthesis of 2-(azidomethyl)oxazoles

• Thaís A. Rossa,
• Nícolas S. Suveges,
• Marcus M. Sá,
• David Cantillo and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2018, 14, 506–514, doi:10.3762/bjoc.14.36

• 1,4-disubstituted triazoles 8 through click reaction between 2-azidomethyl-4,5-diaryloxazoles and alkynes in the presence of a copper(I) catalyst (Scheme 2). The authors were able to synthesize an array of small-molecule peptidomimetics that inhibited Porphyromonas gingivalis biofilm formation [34

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• synthetic tetrasaccharide, to which other species were then conjugated by click reactions. In more recent examples conversion of the completely deprotected glycan to the oxazoline by treatment with DMC has become the normal (and most effective) strategy. For example the same key Manβ(1–4)GlcNAc disaccharide

• formation. Wangs’s total synthesis of an N-glycan oxazoline incorporating click handles, employing Crich direct β-mannosylation. Wangs’s total synthesis of an N-glycan dodecasaccharide oxazoline employing final step oxazoline formation with DMC. Production of a phosphorylated N-glycan oxazoline, employing

Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• [22]. There are not many transformations of aliphatic SF5 compounds described in the literature. Among them are the preparation and derivatization of SF5-aldehydes [23], Diels–Alder reactions [24][25][26], the “click reaction” of SF5-acetylenes with azides to form triazoles [27], and 1,3-dipolar

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• autofluorescence by time-resolved fluorescence measurements. A few monomer–excimer switching PNA probes have been reported. Two or more pyrene labels may be conveniently placed anywhere in the PNA molecule by attaching them to a C5-functionalized thymine via amide or click chemistries, and applications for the

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

• glycoscience. In this review we present recent advances made in the use of one type of click chemistry, namely the azide–alkyne Huisgen cycloaddition, for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles. Keywords: azide–alkyne Huisgen cycloaddition; carbohydrates

• ; click chemistry; glyco-gold nanoparticles; triazole; Introduction Metal nanoparticles (NPs), with their unique physicochemical properties, have drawn significant interest in recent years, and are expected to form the basis of many biological and technological innovations during the remainder of the

• , recent use of click chemistry for the functionalization of AuNPs and their conversion to GAuNPs has increased significantly. This short review, after giving a brief introduction to general methods for GAuNP synthesis, will focus on both potential advantages and issues of using click chemistry for the

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

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

• -the art methods and give directions for choosing the appropriate approach. We also discuss the preparation and properties of mRNAs with non-natural caps providing novel features such as improved stability or enhanced translational efficiency. Keywords: cap analogue; cap synthesis; click chemistry

• structure of Ecm1 which forms a substrate binding cleft rather than a pocket [94]. Vinylbenzyl-modified cap analogues (bearing the modification at either the N7 or N2-position) provided a platform for inverse electron-demand Diels–Alder reactions with tetrazine conjugates and for photo-click reactions using

• preparation of long and cap modified RNAs. Using this system, several biologically relevant RNAs such as GFP RNA, firefly luciferase RNA and m7Gpppm6Am-RNA were produced [118][119]. Click chemistry for the preparation of capped RNAs and cap analogues As an alternative to preparation of longer RNA via IVT

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

• Engineering and Technology, University of Zagreb, Marulićev trg 20, HR-10000 Zagreb, Croatia University of Zagreb, Faculty of Textile Technology, Department of Applied Chemistry, Prilaz baruna Filipovića 28a, HR-10000 Zagreb, Croatia 10.3762/bjoc.13.232 Abstract Copper-catalyzed mechanochemical click

• 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

• an efficient regioselective generation of 1,4-disubstituted 1,2,3-triazoles [1][2][3]. After their discovery [1], click reactions affording 1,2,3-triazoles rapidly became important for simple and robust binding of versatile molecules and for the building of stable polymer structures [4]. At the same

Synthesis and application of trifluoroethoxy-substituted phthalocyanines and subphthalocyanines

• Satoru Mori and
• Norio Shibata

Beilstein J. Org. Chem. 2017, 13, 2273–2296, doi:10.3762/bjoc.13.224

• ] or trifluoroethoxy (12) [82] group have been reported. These dimers were synthesized from A3B type phthalocyanines containing an ethynyl group and 1,4-bis(azidomethyl)benzene via a so-called “double-click reaction” [83] catalyzed by CuI. The examination of the spectroscopic properties of these dimers

• the repulsive effect of the trifluoroethoxy group. More interestingly, similar aggregation behaviors were also suggested for trinuclear phthalocyanines that can aggregate more easily [84]. These trinuclear phthalocyanines were synthesized by a triple click reaction. The tert-butyl-substituted trimer

• TFEO-ZnPc 4 and fluorinated polymer 22 were condensed by a click reaction between azide and alkyne groups (Scheme 8). The graft ratio of the TFEO-ZnPc-supported fluoropolymer was calculated from the area ratio of 19F NMR, and the resulting fluorinated copolymers showed different grafting ratios (from