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

• pharmacophoric conjugates through CuAAC. Basically, these conjugates included cholesterol and 1,2,3-triazole moieties, while the third, the pharmacophore, was either a chalcone, a lipophilic residue or a carbohydrate tag. These compounds were successfully prepared in good yields and characterized by NMR, MS and

• conditions used to prepare compound 2. This step aimed to have an alkylating probe that might target nucleic acids or proteins in the tested biological systems. The 1,2,3-triazole-bridged bicholesterol 13 (Scheme 3) was prepared in excellent yield. The H-5 signal of triazole (1H NMR) also was observed as

Synthesis and spectroscopic properties of β-triazoloporphyrin–xanthone dyads

• Dileep Kumar Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2015, 11, 1434–1440, doi:10.3762/bjoc.11.155

• –tetrathiafulvalenes [14], porphyrin–cyanines [15], porphyrin–carotenes [16], porphyrin–arene diimide [17] and porphyrin–fluorocene or rhodamine [18] have also been synthesized in which the porphyrin unit acts as an electron acceptor. Recently, the 1,2,3-triazole scaffold has been successfully employed to connect

Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition

• Zachary L. Palchak,
• Paula T. Nguyen and
• Catharine H. Larsen

Beilstein J. Org. Chem. 2015, 11, 1425–1433, doi:10.3762/bjoc.11.154

• –alkyne (KA2) coupling that proceeds efficiently with no additives such that an equivalent of water is the sole byproduct. This two-step sequence allows for the incorporation of tetrasubstituted carbons bearing amines at the 4-position of the 1,2,3-triazole core. The overall yield of this three-reaction

• (blue). KA2 coupling followed by tandem silyl deprotection and triazole formation. Silyl deprotection/click conditions applied to tert-butylacetylene. An identical yield is observed without TBAF. High overall yield of 1,2,3-triazole fully-substituted at the 4-position. Optimization of silyl deprotection

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• ). More recently, the Jamison group also reported upon a short flow synthesis of the antiepileptic agent rufinamide (95) [87]. The 1,2,3-triazole ring was prepared via a dipolar cycloaddition between an in situ generated benzylic azide and propiolamide (also prepared in situ), which by maintaining a low

Quarternization of 3-azido-1-propyne oligomers obtained by copper(I)-catalyzed azide–alkyne cycloaddition polymerization

• Shun Nakano,
• Akihito Hashidzume and
• Takahiro Sato

Beilstein J. Org. Chem. 2015, 11, 1037–1042, doi:10.3762/bjoc.11.116

• . Keywords: 3-azido-1-propyne oligomer; CuAAC polymerization; hydrodynamic radius; methyl iodide; pulse-field-gradient spin-echo NMR; quarternization; Introduction The copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) efficiently yields 1,4-disubstituted-1,2,3-triazole from rather stable azides and

• chemistry [8][9][10][11][12] to materials science [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29], as well as polymer synthesis [30][31][32][33][34][35][36]. Most of these studies deal with the 1,2,3-triazole moiety just as a linker. However, since 1,2,3-triazole possesses a large

• dipole moment and aromaticity, 1,2,3-triazole itself may be a functional group. Polymers composed of dense 1,2,3-triazole moieties on the backbone are thus promising as functional materials. Recently, we have investigated the CuAAC polymerization of 3-azido-1-propyne (AP) using 3-bromo-1-propyne as a

C-5’-Triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides: Synthesis and biological evaluation

• Roberto Romeo,
• Caterina Carnovale,
• Salvatore V. Giofrè,
• Maria A. Chiacchio,
• Adriana Garozzo,
• Emanuele Amata,
• Giovanni Romeo and
• Ugo Chiacchio

Beilstein J. Org. Chem. 2015, 11, 328–334, doi:10.3762/bjoc.11.38

• can interact with intracellular targets to induce cytotoxicity [28][29][30][31][32]. Several functionalities have been inserted as linkers on the 2’-oxa-3’-aza-4’a-carbanucleoside skeleton in order to confer novel mechanisms of action for nucleoside mimics: in this context, the 1,2,3-triazole unit

• , the 1,2,3-triazole motif is exceedingly stable to basic or acidic hydrolysis and interacts strongly with biological targets through hydrogen bonding to nitrogen atoms as well as through dipole–dipole and π-stacking interactions [39]. Recently, a synthetic approach towards 3-hydroxymethyl-5-(1H-1,2,3

• -triazol)-isoxazolidines 5 has been described [40]: the obtained compounds inhibit the growth of anaplastic and follicular human thyroid cancer cell lines, with IC50 values in the range of 3.87–8.76 μM. In the same context, novel 1,2,3-triazole-appended 2’-oxa-3’-azanucleoside analogs 6 were developed [41

Articulated rods – a novel class of molecular rods based on oligospiroketals (OSK)

• Pablo Wessig,
• Roswitha Merkel and
• Peter Müller

Beilstein J. Org. Chem. 2015, 11, 74–84, doi:10.3762/bjoc.11.11

• defined a 1,2,3-triazole containing linkage between two piperidine rings as the flexible joint F, which should be easily accessible by copper-catalyzed cycloaddition between an azide G and a terminal alkyne H (CuAAC, “Click” reaction) [16]. Primary alcohols I serve as “protected” azides accessible by

• linked by a flexible joint. The deciding feature of ARs is the equilibrium between two leading conformations: a straight (STR) and a folded (FOL) species. The joint contains a 1,2,3-triazole moiety and the synthesis was carried out by copper catalyzed alkyne/azide cycloaddition (CuAAC). To obtain ARs

The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde

• Volodymyr V. Tkachenko,
• Elena A. Muravyova,
• Sergey M. Desenko,
• Oleg V. Shishkin,
• Svetlana V. Shishkina,
• Dmytro O. Sysoiev,
• Thomas J. J. Müller and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2014, 10, 3019–3030, doi:10.3762/bjoc.10.320

• -aminotetrazole [9], 5-aminopyrazoles [11], and 5-amino-1,2,3-triazole [12] have previously been investigated. In some cases when the reaction could proceed in two alternative pathways the conditions enabling to control the interaction direction were determined, which made it possible to obtain the desired

Synthesis and characterization of a new photoinduced switchable β-cyclodextrin dimer

• Florian Hamon,
• Claire Blaszkiewicz,
• Marie Buchotte,
• Estelle Banaszak-Léonard,
• Hervé Bricout,
• Sébastien Tilloy,
• Eric Monflier,
• Christine Cézard,
• Laurent Bouteiller,
• Christophe Len and
• Florence Djedaini-Pilard

Beilstein J. Org. Chem. 2014, 10, 2874–2885, doi:10.3762/bjoc.10.304

• ]. As an exception, Vargas et al. [29] described the synthesis of 1,2,3-triazole-linked azobenzene-cyclodextrin derivatives producing rather good yields but the photoisomerization and inclusion complex properties were not investigated. Here, we report an efficient preparation of a new bis-β-CD with

A small azide-modified thiazole-based reporter molecule for fluorescence and mass spectrometric detection

• Stefanie Wolfram,
• Hendryk Würfel,
• Stefanie H. Habenicht,
• Christine Lembke,
• Phillipp Richter,
• Eckhard Birckner,
• Rainer Beckert and
• Georg Pohnert

Beilstein J. Org. Chem. 2014, 10, 2470–2479, doi:10.3762/bjoc.10.258

• bioactive metabolites and selective labeling of proteins and other biomacromolecules. A common structural motif for such probes consists of a reporter that can be attached by copper(I)-catalyzed 1,2,3-triazole formation between terminal alkynes and azides to a reactive headgroup. Here we introduce the

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• ][1,2,3]triazole, via in situ formation of pyrrolidine enamines and Pd catalysis. Keywords: alkoxy; azabenzotriazole; benzotriazole; peptide-coupling; phosphonium; Introduction Benzotriazole derivatives are of importance in diverse contexts. As examples, in medicinal chemistry substituted benzotriazoles

• [29]. Although BOP did not react with MeOH in the absence of a base, in the presence of Cs2CO3 rapid formation of HMPA was observed and 1-methoxy-1H-benzotriazole (1-methoxy-1H-benzo[d][1,2,3]triazole) was isolated [29]. This evidence clearly showed that alcohols are capable of reaction with BOP in

• experiments gave poorer results with a lower amount of an alcohol, then reactions were conducted with higher excesses of the alcohol. Specific experimental and work-up details are provided under the individual compound headings. Representative examples 1-(1-Phenylethoxy)-1H-benzo[d][1,2,3]triazole (1e) The

Microwave-assisted Cu(I)-catalyzed, three-component synthesis of 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles

• Yogesh Kumar,
• Vijay Bahadur,
• Anil K. Singh,
• Virinder S. Parmar,
• Erik V. Van der Eycken and
• Brajendra K. Singh

Beilstein J. Org. Chem. 2014, 10, 1413–1420, doi:10.3762/bjoc.10.145

• several existing drugs. Various medicinal agents are composed of several heterocyclic rings in which the benzimidazole and the 1,2,3-triazole constitute an important position. Benzimidazole derivatives have been shown to posses anticancer [1][2], antihypertensive [3], antibacterial [4] and enzyme

Design and synthesis of multivalent neoglycoconjugates by click conjugations

• Feiqing Ding,
• Li Ji,
• Ronny William,
• Hua Chai and
• Xue-Wei Liu

Beilstein J. Org. Chem. 2014, 10, 1325–1332, doi:10.3762/bjoc.10.134

• construction of a 1,4-disubstituted-1,2,3-triazole unit via a copper(I)-catalyzed modern version of the Huisgen-type azide–alkyne cycloaddition [6][7][8][9][10] has been considered to be a powerful ligation method for glycoconjugation [11][12][13][14][15][16]. In addition to the simplicity of this reaction and

• the presence of 10 mol % of copper(I) iodide (Table 1, entry 4). The combination of CuSO4·5H2O (10 mol %) and sodium ascorbate (10 mol %) was found to be a suitable catalyst leading regiospecifically to the 1,4-disubstituted-1,2,3-triazole 4a with moderate yield of 46% in t-BuOH/H2O 1:1 after 20 hours

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

• Regina Berg and
• Bernd F. Straub

Beilstein J. Org. Chem. 2013, 9, 2715–2750, doi:10.3762/bjoc.9.308

• with quantitative conversion to give the 1,4-disubstituted 1,2,3-triazole exclusively. Common side reactions such as the Glaser coupling [9][10][11] are not observed. The presented reaction conditions are compatible with a variety of functional groups such as ester, ether, amide, thioether, Fmoc and

• , sulfonamide and amine substituents. The catalytic process is insensitive towards the presence of air and pH changes between pH 4 and 12 in a solvent mixture of water and tert-butanol. This strictly regioselective stepwise process gives the 1,4-disubstituted 1,2,3-triazole only and accelerates the reaction by

• , the azide substrates could be prepared in situ by reaction of the corresponding bromide with sodium azide. For example, the reaction of benzyl bromide with sodium azide and phenylacetylene in the presence of 2 mol % [(SIMes)CuBr] in water gave 86% 1-benzyl-4-phenyl-1H-1,2,3-triazole within 18 hours at

Ambient gold-catalyzed O-vinylation of cyclic 1,3-diketone: A vinyl ether synthesis

• Yumeng Xi,
• Boliang Dong and
• Xiaodong Shi

Beilstein J. Org. Chem. 2013, 9, 2537–2543, doi:10.3762/bjoc.9.288

• addition to the alkyne besides the typical π-acid activation [12][13][14][15][16][17]. Our group has developed the 1,2,3-triazole coordinated gold complexes (TA-Au) as stable catalysts for alkyne activation in the past several years [26][27][28][29][30]. Considering that TA-Au complexes might have

Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

• Sándor B. Ötvös,
• Ádám Georgiádes,
• István M. Mándity,
• Lóránd Kiss and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1508–1516, doi:10.3762/bjoc.9.172

• Sandor B. Otvos Adam Georgiades Istvan M. Mandity Lorand Kiss Ferenc Fulop Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary 10.3762/bjoc.9.172 Abstract The preparation of novel multi-substituted 1,2,3-triazole-modified β-aminocyclohexanecarboxylic

• safe and straightforward way. The obtained 1,2,3-triazole-substituted β-aminocyclohexanecarboxylates can be regarded as interesting precursors for drugs with possible biological effects. Keywords: β-amino acids; click chemistry; continuous-flow; copper; flow chemistry; triazoles; Introduction In

• recent years, triazole-containing compounds have become potential targets for drug discovery [1][2]. A large number of 1,2,3-triazoles exhibit various biological effects [3], e.g., antiviral (1), antibacterial (2), antifungal (3) and anticancer (4) activities [4][5][6][7] (Figure 1). The 1,2,3-triazole

A versatile and efficient approach for the synthesis of chiral 1,3-nitroamines and 1,3-diamines via conjugate addition to new (S,E)-γ-aminated nitroalkenes derived from L-α-amino acids

• Vera Lúcia Patrocinio Pereira,
• André Luiz da Silva Moura,
• Daniel Pais Pires Vieira,
• Leandro Lara de Carvalho,
• Eliz Regina Bueno Torres and
• Jeronimo da Silva Costa

Beilstein J. Org. Chem. 2013, 9, 832–837, doi:10.3762/bjoc.9.95

• the other hand, the azide anion reacted with 2a, in acetonitrile, via a [3 + 2]-cycloaddition in which HNO2 was lost, providing the corresponding 1,2,3-triazole derivative. Direct reduction of 1,3-nitroamine derivatives 9a,b produced the corresponding 1,3-diamines in good yields. Keywords: amino

• -derivatives 10b,c (Table 1, entries 11 and 12) or the triazole derivative 11a (Table 1, entry 13) when THF or CH3CN were used as solvents, respectively. The formation of chiral 1,2,3-triazole derivative 11a was proposed to be by way of a [3 + 2]-cycloaddition with the azide group acting as 1,3-dipolarophile

• , followed by HNO2 elimination leading to aromatization. There are a few reports in the literature where the azide anion is added to α,β-unsaturated nitroalkenes [8][19][20][21][22] forming 1,4-adducts [8] or 1,2,3-triazole derivatives [31][32][33]. Apparently, the reaction course depends on the temperature

Spin state switching in iron coordination compounds

• Philipp Gütlich,
• Ana B. Gaspar and
• Yann Garcia

Beilstein J. Org. Chem. 2013, 9, 342–391, doi:10.3762/bjoc.9.39

Features of the behavior of 4-amino-5-carboxamido-1,2,3-triazole in multicomponent heterocyclizations with carbonyl compounds

• Eugene S. Gladkov,
• Katerina A. Gura,
• Svetlana M. Sirko,
• Sergey M. Desenko,
• Ulrich Groth and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2012, 8, 2100–2105, doi:10.3762/bjoc.8.236

• similar MCRs of numerous other aminoazoles, a change of direction of the heterocyclizations in the case of 4-amino-5-carboxamido-1,2,3-triazole was not observed when microwave or thermal heating was substituted by ultrasonication at ambient temperature. Keywords: 4-amino-5-carboxamido-1,2,3-triazole

• polyfunctional aminoazoles that have been studied in heterocyclization reactions [5][6][7][8][20], derivatives of 4-amino-1,2,3-triazole have been less well investigated. There are only a few examples of their heterocyclizations with β-diketones [21], N-cyanomethaneimidates [22], isocyanates [23], chalcones [24

• ] and derivatives of carboxylic acids [25][26]. The only MCR involving this type of aminoazole was described in our previous publication [27]. In the case of 4-amino-5-carboxamido-1,2,3-triazole, heterocyclizations can proceed in two main ways: “classical” for α-aminoazole direction with participation

Copper-catalyzed CuAAC/intramolecular C–H arylation sequence: Synthesis of annulated 1,2,3-triazoles

• Rajkumar Jeyachandran,
• Harish Kumar Potukuchi and
• Lutz Ackermann

Beilstein J. Org. Chem. 2012, 8, 1771–1777, doi:10.3762/bjoc.8.202

• sequential synthesis of 1,4-dihydrochromeno[3,4-d][1,2,3]triazole (4b, Scheme 2). We were delighted to observe that the desired reaction sequence consisting of a copper-catalyzed 1,3-dipolar cycloaddition and an intramolecular C–H bond arylation converted alkyne 1a to the desired product 4b with high

Thiophene-based donor–acceptor co-oligomers by copper-catalyzed 1,3-dipolar cycloaddition

• Stefanie Potratz,
• Amaresh Mishra and
• Peter Bäuerle

Beilstein J. Org. Chem. 2012, 8, 683–692, doi:10.3762/bjoc.8.76

• polymers [21][22][23], and was used for DNA labelling [24][25], sensors [26][27], and metal chelates [28][29][30], due to the mild reaction conditions and compatibility with a variety of functional groups. However, the electronic conjugation through the resulting 1,2,3-triazole rings is weak due to poor

• electronic communication between the chromophores [21][22][23][31]. It has also been shown that a 1,2,3-triazole can act as a strong σ-electron donor [26] or as a weak π-electron acceptor [15]. In this study, we aimed at the combination of electron-rich (oligo)thiophenes as donors and electron-deficient

• 1,2,3-triazole rings as acceptors to conveniently build up novel donor–acceptor co-oligomeric and copolymeric materials by click chemistry. Thereby, the inherent instability of 2-azidothiophene was a problem. Results and discussion In 2005, Liang et al. [32] described a mild, copper-catalyzed method to

A ferrocene redox-active triazolium macrocycle that binds and senses chloride

• Nicholas G. White and
• Paul D. Beer

Beilstein J. Org. Chem. 2012, 8, 246–252, doi:10.3762/bjoc.8.25

• that the redox-active macrocycle is capable of sensing chloride in CH3CN solution. Keywords: anion binding; C–H···anion interactions; electrochemistry; ferrocene; triazolium; Introduction The copper(I)-catalysed cycloaddition of alkynes and azides (CuAAC) [1][2] to give the 1,2,3-triazole group is

Synthesis of 2-amino-3-arylpropan-1-ols and 1-(2,3-diaminopropyl)-1,2,3-triazoles and evaluation of their antimalarial activity

• Matthias D’hooghe,
• Stéphanie Vandekerckhove,
• Karen Mollet,
• Karel Vervisch,
• Stijn Dekeukeleire,
• Liesbeth Lehoucq,
• Carmen Lategan,
• Peter J. Smith,
• Kelly Chibale and
• Norbert De Kimpe

Beilstein J. Org. Chem. 2011, 7, 1745–1752, doi:10.3762/bjoc.7.205

• approach is disclosed towards racemic aminopropanes 4 bearing a 1,2,3-triazole moiety, as structural analogues of the previously reported 1,2,4-triazoles 2 (Figure 1). Both classes of functionalized aminopropanes 3 and 4 were tested for their antiplasmodial activity. Results and Discussion Synthesis Within

• 1,2,3-triazole moiety instead. A powerful methodology towards the synthesis of functionalized 1,2,3-triazoles involves the Cu(I)-catalyzed azide-alkyne Huisgen cycloaddition (CuAAC) [33], which has gained major interest from the synthetic community due to its high efficiency and selectivity. Eligible

Highly efficient cyclosarin degradation mediated by a β-cyclodextrin derivative containing an oxime-derived substituent

• Michael Zengerle,
• Florian Brandhuber,
• Christian Schneider,
• Franz Worek,
• Georg Reiter and
• Stefan Kubik

Beilstein J. Org. Chem. 2011, 7, 1543–1554, doi:10.3762/bjoc.7.182

• with 2-formylpyridine oxime or 2-acetylpyridine oxime, unfortunately failed to produce the desired products. The cyclodextrin derivatives 2a–d contain 1,4-disubstituted 1,2,3-triazole moieties as the linking units. Accordingly, they were prepared by copper(I)-catalyzed azide–alkyne cycloaddition

Triazole–Au(I) complex as chemoselective catalyst in promoting propargyl ester rearrangements

• Dawei Wang,
• Yanwei Zhang,
• Rong Cai and
• Xiaodong Shi

Beilstein J. Org. Chem. 2011, 7, 1014–1020, doi:10.3762/bjoc.7.115

• significant challenge in gold catalysis. Results and Discussions Recently, our group reported the synthesis and characterization of the 1,2,3-triazole [36][37][38][39][40] coordinated gold(I) complexes. As revealed by the X-ray crystal structures (Scheme 3), both neutral and anionic triazoles can coordinate

• the synthesis of allenes through gold activated alkynes. X-ray crystal structures of the two different types of 1,2,3-triazole–Au complexes. Synthesis of α-iodoenone compounds from propargyl esters. The reaction substrate scope.a Different migrating groups.a Supporting Information Supporting