Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• the removal of metathesis catalysts is the formation of Ru-DMSO complexes, which do not eluate from a silica column [56]. This allowed us to remove at least the Ru contamination, but we were unable to subject 12 to further modifications such as cross metathesis or thiol-ene click reactions due to poor

• modifications, mainly for solubility reasons. Therefore, we decided to have a closer look into modifications of the longer side chain present in 11 and subjected it to thiol-ene click reactions. Since masked thiols are often found as zinc-coordinating functionalities in HDAC inhibitors, e.g., in the largazoles

• , we treated 11 with thioacetic acid and BEt3/air in THF to give 82% of the thiol-ene click product (Scheme 4). Careful analysis of the NMR spectra revealed that the intermediately formed radical cyclized in an intramolecular 5-exo-trig fashion with the internal double bond to form a tetrahydrofuran

Polymer chemistry: fundamentals and applications

• Bernhard V. K. J. Schmidt

Beilstein J. Org. Chem. 2021, 17, 2922–2923, doi:10.3762/bjoc.17.200

• materials [6]. This thematic issue covers a broad range of current topics in polymer chemistry, from synthesis to materials and applications. In the area of synthetic methods, the use of click photochemistry in polymer and organic molecule synthesis is presented, as well as the combination of polymers with

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• ]. The main approach in the synthesis of the tetrazoles is 1,3-dipolar cycloaddition between azide and nitrile. These reactions often follow the principles of “click” chemistry [20]. Although the formation of tetrazole in the Schmidt reaction of ketones was noted in the original study by Schmidt himself

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• such as antimicrobial properties. A work reported by Koshy et al. in 2018 was testing the use of injectable nanocomposite cryogels for versatile protein-drug delivery [37]. Injectable and porous cryogels were prepared using a bio-orthogonal click chemistry crosslinking approach with alginate employing

• tetrazine-norbornene coupling. Laponite nanoparticles were then incorporated within the walls of the cryogel. The results showed the so-called “click alginate” was able to produce cryogels with an interconnected porous structure, and high deformability allowing it to be used through a 16-gauge needle. The

Exfoliated black phosphorous-mediated CuAAC chemistry for organic and macromolecular synthesis under white LED and near-IR irradiation

• Azra Kocaarslan,
• Zafer Eroglu,
• Önder Metin and
• Yusuf Yagci

Beilstein J. Org. Chem. 2021, 17, 2477–2487, doi:10.3762/bjoc.17.164

• , Turkey King Abdulaziz University, Faculty of Science, Chemistry Department, 21589 Jeddah, Saudi Arabia 10.3762/bjoc.17.164 Abstract The development of long-wavelength photoinduced copper-catalyzed azide–alkyne click (CuAAC) reaction routes is attractive for organic and polymer chemistry. In this study

• molecular properties of the intermediates and final products were evaluated by spectral and chromatographic analyses. Keywords: black phosphorus; click chemistry; heterogeneous photocatalyst; near infrared; phosphorene; Introduction For the last decade, click chemistry has been recognized as an

• indispensable part of synthetic chemistry due to its easiness of application, efficiency to produce the targeted products with very high yields and little or no byproducts under a variety of conditions, and high interconnected group tolerance. Since the introduction of click chemistry by Sharpless [1][2] and

Synthesis and antimicrobial activity of 1H-1,2,3-triazole and carboxylate analogues of metronidazole

• Satya Kumar Avula,
• Syed Raza Shah,
• Khdija Al-Hosni,
• Muhammad U. Anwar,
• Rene Csuk,
• Biswanath Das and
• Ahmed Al-Harrasi

Beilstein J. Org. Chem. 2021, 17, 2377–2384, doi:10.3762/bjoc.17.154

• . The structure of metronidazide 3 was unambiguously confirmed by single crystal X-ray analysis (Figure 3). The next step was carried out by using “click” chemistry involving the 1,3-dipolar cycloaddition reaction between metronidazide 3 and alkyne derivative 4a in the presence of CuI and Hünig’s base

• transformations of novel metronidazole 1H-1,2,3-triazole derivatives via “click” chemistry and carboxylate derivatives can lead to a wide range of biological applications. Antimicrobial activity The general structural pattern of the synthesized metronidazole derivatives is shown in Figure 6. Two pharmacophoric

• metronidazole. Conclusion In summary, a series of novel metronidazole 1H-1,2,3-triazole and carboxylate derivatives (5a–i and 7a–e) were synthesized via “click” chemistry, and evaluated for their antimicrobial activity (antifungal and antibacterial) in vitro. All the synthesized compounds (except 2 and 3 for

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• analogs [12][13], in this work, we designed a series of imatinib 1,2,3-triazole analogs 1a,b and 2a–j (Figure 1). The 1,2,3-triazoles are heterocyclic compounds, consisting of a five-membered ring, containing two carbon atoms and three nitrogen atoms [14]. The application of click chemistry, a concept

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• to 2-bromoazulene (147) and subsequently to the TMS acetylene derivative 148 suitable for the ‘click’ reaction [46] to obtain the triazole 149, which was eventually transformed into the triazole-containing azulene methacrylate monomer 150 (Scheme 25B). The monomers 146 and 150 were then subjected to

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• further modifications, for example by click-chemistry [82]. These results show that enzymatic methods can be powerful approaches also to create unnatural polysaccharide materials. Nevertheless, the inherent selectivity of the enzymes limits these approaches to particular patterns and modifications. To

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• incorporated into TFOs all induced excellent triplex stability at pH 7.0 [94] (Table 6). To circumvent the laborious work related to the monomers described above, post-ON conjugation via click-chemistry was utilized to attach two different spermidine analogues, carrying either two (56) or three (57) positive

• them ideal ASO modifications as only a limited number of modifications is needed for a substantial effect. Recently, a versatile method of post-ON synthesis conjugation, different from the click chemistry method, has been applied to 2’-amino-LNA. A class of 2’-urea-LNA analogues (58–62) has been

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• , demonstrating significant bioorthogonality in manganese(I) catalysis. The robustness of the method bears significance for further synthetic applications, such as “Click” chemistry or N-functionalization. Moreover, as shown in Scheme 9B, the manganese(I) catalysis regime enabled peptide macrocyclization (see 25f

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• industry. The current review aims to cover a wide literature survey of numerous synthetic strategies. Recent reports (2017–2021) in the field of 1,4,5-trisubstituted 1,2,3-triazoles are emphasized in this current review. Keywords: azides; Click reaction; [3 + 2]‐cycloaddition; fully functionalized 1,2,3

• fully decorated triazoles. As shown in Figure 1, 1,4,5-trisubstituted 1,2,3-triazole derivatives display a privileged class of fully decorated triazoles in Click chemistry extensively found in many biologically important compounds and functionalized frameworks. In this regard, the discovery of diverse

• . Finally, a reductive elimination takes place to give the corresponding final product and the catalyst for the next run [51]. A tandem Click/intramolecular sulfenylation procedure for the synthesis of sulfur-cycle-fused 1,2,3-triazoles 75 and 77 was described by Xu et al. The reaction was performed through

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

• Maryna O. Mazur,
• Oleksii S. Zhelavskyi,
• Eugene M. Zviagin,
• Svitlana V. Shishkina,
• Vladimir I. Musatov,
• Maksim A. Kolosov,
• Elena H. Shvets,
• Anna Yu. Andryushchenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2021, 17, 678–687, doi:10.3762/bjoc.17.57

• harder while the microwave-assisted catalyst-free conditions were effective for both terminal and non-terminal alkynes. Keywords: click chemistry; microwave chemistry; multicomponent reactions; triazolobenzodiazepines; Ugi reaction; Introduction Benzannulated heterocycles are among the most important

• includes a [3 + 2] click reaction between the azide ion with the triple bond and further C–N coupling instead of the IAAC reaction. Compounds having no fused benzene ring or with a heterocyclic moiety instead could also be obtained via the tandem approach Ugi reaction/IAAC [15][16]. Despite the

• cycloaddition approach to the synthesis of 1,2,3-triazolobenzodiazepinones. Results and Discussion The development of the tandem Ugi/Click reaction approach for 1,2,3-triazolobenzodiazepinone synthesis can be logically divided into two principal parts: modification and performing synthesis of Ugi-reaction

Deoxygenative C2-heteroarylation of quinoline N-oxides: facile access to α-triazolylquinolines

• Geetanjali S. Sontakke,
• Rahul K. Shukla and
• Chandra M. R. Volla

Beilstein J. Org. Chem. 2021, 17, 485–493, doi:10.3762/bjoc.17.42

• -catalyzed “Click” chemistry, N-sulfonyl-1,2,3-triazoles have become useful precursors for accessing a variety of heterocyclic moieties [55][56]. In spite of the above methods for the C2-amination, the establishment of a simple, efficient and atom-economical method for the synthesis of 2-triazolylquinoline

• derivatives, we performed a sequential one-pot synthesis by combining a Cu(I)-catalyzed “Click” reaction of phenylacetylene (7) with TsN3 and a metal-free C2-heteroarylation of quinoline N-oxide (1a, Scheme 6b). Remarkably, the yield of the desired product 3a in the one-pot synthesis (80%) was comparable to

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• , the two self-sorting protocols also cleanly happened in the presence of the substrates 32 and 33. However, now in state SelfSORT-II, the nanorotor [Cu2(31)(28)]2+ acted as a copper(I)-based catalyst for the click reaction of 32 and 33 affording the product 34, whereas in state SelfSORT-I, no

• + + [Cu2(40)2]2+ + 2 × [Cu(42)]+ (= SelfSORT-II). With SelfSORT-I containing the heterocycle 42, a known organocatalyst, and SelfSORT-II holding the potential click catalyst [Cu(42)]+, it was speculated that both networked states could be catalytically active thus allowing the ON/OFF regulation of a dual

• but no click product 48 was observed (Figure 14b). The addition of 1.0 equiv of zinc(II) ions (with respect to the rotor) generated the state SelfSORT-II. After heating this mixture using the identical conditions, 55% of the click product 48 was detected but no further conversion of the product 45

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• berberine derivatives was synthesized by the Cu-catalyzed click reaction of 9-propargyladenine with 9-O-(azidoalkyl)berberine derivatives. The association of the resulting berberine–adenine conjugates with representative quadruplex-forming oligonucleotides 22AG dA(G3TTA)3G3 and a2 d(ACAG4TGTG4)2 was

• -forming repeat unit from the “insulin-linked polymorphic region” (ILPR) [50], that was also shown to bind quadruplex ligands [51]. Results Synthesis As the Cu-catalyzed click reaction between azides and alkynes is a well-established method for the variable functionalization of G4-DNA ligands [52], the

Computational tools for drawing, building and displaying carbohydrates: a visual guide

• Kanhaya Lal,
• Rafael Bermeo and
• Serge Perez

Beilstein J. Org. Chem. 2020, 16, 2448–2468, doi:10.3762/bjoc.16.199

• the “Essentials of Glycobiology Symbol Nomenclature”, precursor of the SNFG symbol set [55]. The interface provides a wide choice of monosaccharides and substituents represented in SNFG symbols but lacks the standard colour scheme. The user can easily modify the structure with by click and drag, which

• the rest can be found categorised by family. The click and drag addition of new monosaccharides trigger the selection of linkage-type and configuration (Figure 7, bottom). The tool provides an option to create repeating units. Additionally, several functionalisation options are also available. Once

Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots

• Elizabeth A. Margolis,
• Rebecca J. Keyes,
• Stephen D. Lockey IV and
• Edward E. Fenlon

Beilstein J. Org. Chem. 2020, 16, 2314–2321, doi:10.3762/bjoc.16.192

• alkyne–azide click cycloaddition as the linking step, and ester saponification as the cutting step [13][21] (Supporting Information File 1). The target trefoil knot using host 1 and guest 2 is shown in Figure 2c. The binding event during the double-threading step was modeled after previous literature

• more than twice as high and this route is more amenable to multigram scale reactions. Azido-bromide 6 can undergo both alkyne–azide click cycloaddition and etherification and the effect of the reaction order on the overall yield was explored next. The click cycloaddition was pursued first and reaction

• changing the order of these steps would be beneficial. Alkylation of terephthalate 12 with azido-bromide 6 using cesium carbonate as the base provided high yields (82%) of core diazide 14 (Scheme 3). Click cycloaddition of 14 with an excess of dialkyne 10 also proceeded in high yields (87%) to give diester

Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents

• Paola Vitale,
• Luciana Cicco,
• Ilaria Cellamare,
• Filippo M. Perna,
• Antonio Salomone and
• Vito Capriati

Beilstein J. Org. Chem. 2020, 16, 1915–1923, doi:10.3762/bjoc.16.158

• (g) heterogeneous “click” cycloaddition reactions [15] using DESs as environmentally responsible and non-innocent reaction media. Telescoped, one-pot transformations of phenacyl halides to symmetrical 2,5-disubstituted pyrazines (A), through phenacyl azides as intermediates, were also found to take

Design, synthesis and application of carbazole macrocycles in anion sensors

• Alo Rüütel,
• Ville Yrjänä,
• Sandip A. Kadam,
• Indrek Saar,
• Mihkel Ilisson,
• Astrid Darnell,
• Kristjan Haav,
• Tõiv Haljasorg,
• Lauri Toom,
• Johan Bobacka and
• Ivo Leito

Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157

• example, a carbazole-urea macrocycle was reported previously [10], however, the binding of anions occurred outside the receptor due to modest dimensions of the macrocyclic cavity. Using click-chemistry, a carbazole-triazole macrocycle, “tricarb”, was prepared that showed the ability to form non-covalent

Nonenzymatic synthesis of anomerically pure, mannosyl-based molecular probes for scramblase identification studies

• Giovanni Picca,
• Markus Probst,
• Simon M. Langenegger,
• Oleg Khorev,
• Peter Bütikofer,
• Anant K. Menon and
• Robert Häner

Beilstein J. Org. Chem. 2020, 16, 1732–1739, doi:10.3762/bjoc.16.145

• moiety for photocrosslinking to MPD-recognizing proteins. The presence of an additional propargyl group provides a way to further derivatize the probe with biotin azide via click-type chemistry [16] for the isolation of protein–lipid adducts using streptavidin resins [10]. To synthesize such molecular

Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization

• Dominik Göbel,
• Marius Friedrich,
• Enno Lork and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139

• emission behavior. Keywords: bromoarylaldehydes; click-chemistry; fluorenes; fluorescence; phosphorescence; Introduction Small organic luminophores exhibiting room-temperature phosphorescence (RTP) have attracted great attention due to promising applications in optoelectronic devices [1][2][3][4][5][6][7

Regioselectively α- and β-alkynylated BODIPY dyes via gold(I)-catalyzed direct C–H functionalization and their photophysical properties

• Takahide Shimada,
• Shigeki Mori,
• Masatoshi Ishida and
• Hiroyuki Furuta

Beilstein J. Org. Chem. 2020, 16, 587–595, doi:10.3762/bjoc.16.53

• -tethered BODIPY derivatives serve as a substrate in the copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction, which is known as “click” reaction, allowing for a biological tissue labelling [35][36]. In addition, ethynyl-substituted BODIPYs yield unique π-conjugated BODIPY-based macrocycles by

• substitution-site-dependent spectral features, for instance, the extent of the bathochromic shifts of the absorption and fluorescence, variable Stokes shift and the emission quantum yields. The TIPS-protected ethynyl groups of these BODIPY dyes can be applied as substrates for the “click” CuAAC reaction toward

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• is to consider the recently published developments (2014–2019) in the synthesis and catalytic applications of copper supported by silica nanocomposites, carbon nanocomposites, and magnetic nanocomposites for expanding the “click” chemistry. Keywords: “click” reaction; copper complexes; reusable

• groups. The intramolecular reaction of an alkyne as a dipolarophile with an azide as a 1,3-dipole to produce the desired 1,2,3-triazole motif is a model of “click” chemistry. The concept of “click” chemistry is an idiom that was developed by Sharpless and Meldal and later by others to describe organic

• definition and fails as a real “click” reaction. Although this cyclization reaction requires elevated temperatures and often yields both the 1,4- and 1,5-regioisomers, the Cu or Ru alkyne–azide cycloaddition falls exactly into the above definition [11]. In this respect, the copper-catalyzed cycloaddition