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

Curcuminoid–BF₂ complexes: Synthesis, fluorescence and optimization of BF₂ group cleavage

• Henning Weiss,
• Jeannine Reichel,
• Helmar Görls,
• Kilian Rolf Anton Schneider,
• Mathias Micheel,
• Michael Pröhl,
• Michael Gottschaldt,
• Benjamin Dietzek and
• Wolfgang Weigand

Beilstein J. Org. Chem. 2017, 13, 2264–2272, doi:10.3762/bjoc.13.223

• decided to synthesise a range of curcuminoids bearing propargyl and pent-1-yn-5-yl ether groups as partners for “click” reactions [26]. We already observed that for the BF2 complex of bispropargyl functionalised bisdemethoxycurcumin, the BF2 group was hydrolysed under regular “click” reaction conditions

• “click” chemistry. ORTEP drawings in side view (left) and top view (right) of complexes 2f (a), 2g (b) and 2h (c). Hydrogen atoms are omitted from top view for clarity. Absorbance (left) and emission (right) spectra of compounds 2a (orange), 2b (black), 2c (blue), 2d (red), 2e (purple), 2f (green), 2g

Superstructures with cyclodextrins: Chemistry and applications IV

• Gerhard Wenz

Beilstein J. Org. Chem. 2017, 13, 2157–2159, doi:10.3762/bjoc.13.215

• magnetic resonance imaging (MRI) [22]. Well-defined fluorescent polyrotaxanes with alternating, threaded cucurbit[6]uril and CD rings were assembled by Fraser Stoddart’s group via an alkyne–azide click reaction exploiting supramolecular catalysis [23][24]. The concurrent radical copolymerization of 1,3

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• attempt to simplify the synthesis of the non-symmetrical tethers, a highly trendy triazole-forming click chemistry was combined with rigid spacers by the Schmidt group. α,α’-Dibromo ortho- and meta-xylene-derived rigid spacers were used in this application, and this approach allowed to investigate the

• size of the macrocycle formed during the glycosylation (Scheme 12) [80][81]. Thioglycoside donor 45 containing a 2-O-propargyl group and acceptor 46 with an azide-containing protecting group were connected using a click reaction to afford the tethered intermediate 47. Upon treatment with NIS/TfOH

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• synthesize the triazole rings with additional 1 equiv of K2CO3 which resulted in >85% of product (Scheme 37b). Mack and co-workers reported another mechanochemical variation of “click” reaction [153][154] where they could isolate 33–90% of triazole derivatives using copper reaction vial in ball mill for 16 h

• particles [146]. Mechanochemical synthesis of 1,2-di-substituted benzimidazoles [149]. Mechanochemical click reaction using an alumina-supported Cu-catalyst [152]. Mechanochemical click reaction using copper vial [155]. Mechanochemical indole synthesis [157]. Mechanochemical synthesis of chromene [158

Influence of the milling parameters on the nucleophilic substitution reaction of activated β-cyclodextrins

• László Jicsinszky,
• Kata Tuza,
• Giancarlo Cravotto,
• Andrea Porcheddu,
• Francesco Delogu and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 1893–1899, doi:10.3762/bjoc.13.184

• derivative and is used in analytical chemistry as chiral stationary phase [6]. CDs functionalized with triazole substituents can be similarly prepared through click reactions involving the azido group as a dipolarophile [7], and utilized as suitable starting material to access hydroxy functionality after

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• enabled the quantitative synthesis of (thio)ureas and guanidines without using bulk solvents and the generation of byproducts, but it has also been established as a means to develop "click-type" chemistry for these classes of compounds and the concept of small molecule desymmetrization. Moreover

• '-disubstituted thioureas in quantitative yields. In contrast to mortar-and-pestle synthesis, automated ball milling at 30 Hz using a single 12 mm stainless steel ball afforded the desired products quantitatively in 10 minutes, demonstrating its efficiency for a rapid and general synthesis of thioureas via click

• -withdrawing aryl isothiocyanates with anilines used for the synthesis of N,N'-disubstituted thioureas, thorough mixing in an agate mortar typically leads to the formation of the products in a couple of minutes. As an extension of the mechanochemical click-coupling of amines with isothiocyanates, the thiourea

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

Biomimetic molecular design tools that learn, evolve, and adapt

• David A Winkler

Beilstein J. Org. Chem. 2017, 13, 1288–1302, doi:10.3762/bjoc.13.125

• characterization facility at CSIRO Manufacturing in Melbourne Australia. This can generate and test hundreds of polymers, nanomaterials, catalysts, or metal organic frameworks in a day. Clearly, certain types of chemistries (benzodiazepines, click reactions, etc.) are amenable to large chemical library synthesis

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• ). Encouragingly, disaccharides LacNAc and lactose derivatives are compatible (Table 6, entries 5 and 6) [84]. Fairbanks and colleagues have also devised a two-step one-pot method to obtain glycosyl click products [85]. The authors utilized 2-azido-1,3-dimethylimidazolium hexafluorophosphate (ADMI) [86], which

• , L-ascorbic acid and applying mild heat, the desired 1,2-trans click triazole could be obtained in good to excellent yield [85]. This reaction was shown to be very robust as not only di- and oligosaccharides can be formed (one example is shown in Scheme 28B), but also cancer-associated MUC1

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

• potential of the new eco-compatible approach for the macrocyclic library generation. Keywords: carbohydrate; click chemistry; diversity-oriented synthesis; macrocycles; ring-closing metathesis; Introduction Macrocycles offer very complex molecular architectures with a diverse range of ring sizes decorated

• blocks were coupled via 1,3-dipolar cycloaddition (click reaction) iteratively through the development of a greener base-free Cu(I)-catalyzed azide–alkyne cycloaddition reaction. The cycloadducts were then converted to macrocycles by Ru-catalyzed cyclization reaction using greener and non-hazards

• ratio of integration of the terminal alkyne proton in the propargyl building block and the characteristic triazole–alkene proton in the cyclo-adducts. The click reaction proceeds under various conditions with a plenty of sources of Cu(I) [19]. We have selected copper iodide (CuI) as Cu(I) source for the

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

• employed for this purpose (i.e., click reaction, amidation, conjugation via carbonyldiimidazol and perfluorophenyl azide (PFPA) photo-coupling) have to be compatible with water, the common medium for AuNP preparation [25][26][27][28][29]. One example of the three-step approach was described by Tian and co