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

• assumes particular interest according to its easily access and the well-known biological activity of many derivatives. In these last years, in fact, triazoles have gained considerable attention in medicinal chemistry, bioconjugation, drug-delivery, and materials science [33][34][35][36][37][38]. Moreover

Sequential decarboxylative azide–alkyne cycloaddition and dehydrogenative coupling reactions: one-pot synthesis of polycyclic fused triazoles

• Kuppusamy Bharathimohan,
• Thanasekaran Ponpandian,
• A. Jafar Ahamed and
• Nattamai Bhuvanesh

Beilstein J. Org. Chem. 2014, 10, 3031–3037, doi:10.3762/bjoc.10.321

• describe a one-pot protocol for the synthesis of a novel series of polycyclic triazole derivatives. Transition metal-catalyzed decarboxylative CuAAC and dehydrogenative cross coupling reactions are combined in a single flask and achieved good yields of the respective triazoles (up to 97% yield). This

• methodology is more convenient to produce the complex polycyclic molecules in a simple way. Keywords: copper(II) acetate; decarboxylative CuAAC; dehydrogenative coupling; fused triazoles; one-pot synthesis; Introduction The copper-catalyzed Huisgen [3 + 2] cycloaddition (or copper-catalyzed azide–alkyne

• cycloaddition, CuAAC) between an organic azide and a terminal alkyne is a well-established strategy for the construction of 1,4-disubstituted 1,2,3-triazoles [1][2][3][4]. In a recent development, this decarboxylative coupling reaction was well documented for the generation of C–C bonds [5]. This method has

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

• spectrum of biological activity [5][6], which led to choose acetoacetamides as perspective methylene-active compounds for further studies of multicomponent reactions. The interactions of 3-oxobutanamides with aldehydes and a number of aminoazoles, namely 3-amino-1,2,4-triazoles [7][8][9][10][11], 5

• azoloazine with high chemo- and regioselectivity [11][13][14][15]. In particular, three-component heterocyclizations involving 3-amino-1,2,4-triazoles or 4-substituted 5-aminopyrazoles yielded either 4,5,6,7-tetrahydroazolo[1,5-a]pyrimidine-6-carboxamides under ultrasonication at room temperature (kinetic

Cyclodextrin–polysaccharide-based, in situ-gelled system for ocular antifungal delivery

• Anxo Fernández-Ferreiro,
• Noelia Fernández Bargiela,
• María Santiago Varela,
• Maria Gil Martínez,
• Maria Pardo,
• Antonio Piñeiro Ces,
• José Blanco Méndez,
• Miguel González Barcia,
• Maria Jesus Lamas and
• Francisco.J. Otero-Espinar

Beilstein J. Org. Chem. 2014, 10, 2903–2911, doi:10.3762/bjoc.10.308

• ]. Specifically, azole-based medications, which include imidazoles (e.g., miconazole, clotrimazole, and ketoconazole) and triazoles (e.g., fluconazole, itraconazole, posaconazole, and voriconazole), inhibit ergosterol synthesis in the cell wall [4]. Fluconazole is considered to be a good therapeutic option for

Synthesis of aromatic glycoconjugates. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger and
• Thomas Ziegler

Beilstein J. Org. Chem. 2014, 10, 2453–2460, doi:10.3762/bjoc.10.256

• focus was on glycosylated amino acid building blocks derived from aspartic acid and from the PNA-like N-(2-aminoethyl)glycine (AEG) backbone to which the sugar moieties were attached through either simple alkyl chains [5][6], amino alcohols [7][8] or 1,2,3-triazoles [9][10][11]. These building blocks

Derivatives of the triaminoguanidinium ion, 3. Multiple N-functionalization of the triaminoguanidinium ion with isocyanates and isothiocyanates

• Jan Szabo,
• Kerstin Karger,
• Nicolas Bucher and
• Gerhard Maas

Beilstein J. Org. Chem. 2014, 10, 2255–2262, doi:10.3762/bjoc.10.234

• (arylideneamino)- and tris(alkylideneamino)guanidinium salts [7][8][9]; these were the first examples of a threefold symmetrical functionalization of the triaminoguanidinium ion. On the other hand, reactions of triaminoguanidinium salts with carboxylic acids generated 4-amino-3-hydrazinyl-1,2,4-triazoles [10][11

• ]. Diversely substituted 1,2,4-triazoles were also obtained from reactions with cyanogen bromide [12], CS2/NaOH [12] and isothiocyanates [13]. In all these cases, cyclization took place after one or two of the three branches of the triaminoguanidinium ion had been functionalized. Reactions of TAG-Cl (1) with

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

• synthesis of 1-alkoxy-1H-benzo[d][1,2,3]triazoles. Three possible mechanisms for the reaction of BOP with oxygen nucleophiles. Possible products in the [18O]-labeling experiments. Two possible products from the reaction of At-OTs with MeOH. Synthesis of acyclic nucleoside-like compounds. Formation of Bt-OR

Synthesis of new, highly luminescent bis(2,2’-bithiophen-5-yl) substituted 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole

• Anastasia S. Kostyuchenko,
• Vyacheslav L.Yurpalov,
• Aleksandra Kurowska,
• Wojciech Domagala,
• Adam Pron and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2014, 10, 1596–1602, doi:10.3762/bjoc.10.165

• that 1,3,4-oxadiazoles [26], 1,3,4-thiadiazole [27] and 1,2,4-triazoles [28][29][30] can be obtained from diacylhydrazines. Thus, 11 and 12 were converted to 2,5-bis(3-decyl-2,2'-bithiophen-5-yl)-1,3,4-oxadiazole (13) and 2,5-bis[4-(hexyloxy)-2,2'-bithiophen-5-yl]-1,3,4-oxadiazole (14) by the reaction

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

• the ease of purification, 1,4-disubstituted-1,2,3-triazoles, the regiospecific product of this reaction, exhibit similarities to the ubiquitous amide moiety found in nature. However, unlike amides, the triazole moiety proved to be robust and resistant to chemical and enzymatic cleavage [17][18][19][20

• parent precursors [33][34][35][36][37][38][39]. Over the years, many structural analogues of this class of antibiotics have been synthesized. In addition, triazoles are considered as peptidic linkage surrogates. Surprisingly, despite the enormous research interests associated with their synthesis, only a

Dimerisation, rhodium complex formation and rearrangements of N-heterocyclic carbenes of indazoles

• Zong Guan,
• Jan C. Namyslo,
• Martin H. H. Drafz,
• Martin Nieger and
• Andreas Schmidt

Beilstein J. Org. Chem. 2014, 10, 832–840, doi:10.3762/bjoc.10.79

• NHCs of indazole which have been generated and applied in heterocyclic synthesis (vide infra) as well as in complex chemistry [13]. Undoubtedly the N-heterocyclic carbenes of imidazole, imidazoline and the triazoles play the most important roles as ligands in metal-organic chemistry [14] or as

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• , oxazoles, thiazoles and triazoles incorporated into peptide structures will be described. Pyrrolidines 2-substituted pyrrolidine-based dipeptide mimics were obtained from an Ugi-4CR followed by a Pd-catalyzed Sn2 cyclization as described by Banfi et al. [51] . Herein, the Ugi reaction provided a small

• lactams (81, 46% over the two steps, Scheme 24). In addition, an even shorter route by utilizing three olefinic Ugi-substrates was also reported. Herein, the ring closing step included a double RCM and resulted in an equal amount of both products 83a and 83b (ratio 1:1) [75][76]. Triazoles The replacement

• of amide bonds by 1,2,3-triazoles, especially the 1,4-disubstituted isomer, provided a wide variety of biological active peptidomimetics. Peptidomimetics containing these triazole cores can serve as blood components [77], anticancer medications [78], inhibitors of cysteine [79] and HIV-1 proteases

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

• but-2-ynedioate and phenyl azide at 100 °C in a sealed tube and suggested that regioisomeric triazoles were formed [1]. However, it was only in the 1960s that Huisgen recognized this type of reaction for its generality, scope and mechanism [2][3][4][5], and coined the term 1,3-dipolar cycloaddition

• . The classical thermal Huisgen cycloaddition of organoazides and alkynes proceeds very slowly even at high temperatures, and gives a mixture of 1,4- and 1,5-disubstituted 1,2,3-triazoles (Scheme 1). In 2002, the groups of Meldal and Sharpless independently discovered a copper-catalyzed variant of

• Huisgen’s azide–alkyne cycloaddition (CuAAC reaction). In fact, the catalytic effect of copper ions had first been mentioned by L’Abbé in 1984 [7], but had henceforth been overlooked until Meldal presented a copper(I)-catalyzed solid-phase synthesis of 1,2,3-triazoles. In this procedure, the terminal alkyne

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• [114] as well as of various arenes and heteroarenes (pyridines, pyrimidines, pyrazines, quinolines, pyrroles, thiophenes, furans, pyrazoles, imidazoles, thiazoles, oxazoles, thiadiazoles, triazoles) [115]. The yields were low to excellent, depending on the substrate (Scheme 12 and Figure 20). Iron(II

Microwave-assisted synthesis of 5,6-dihydroindolo[1,2-a]quinoxaline derivatives through copper-catalyzed intramolecular N-arylation

• Fei Zhao,
• Lei Zhang,
• Hailong Liu,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2013, 9, 2463–2469, doi:10.3762/bjoc.9.285

• , the copper-catalyzed N-arylation has been extensively utilized for C–N coupling, especially for the arylation of N-containing heterocycles such as indoles, imidazoles, indazoles, pyrroles, pyrazoles and triazoles [25][26][27][28] to construct more fused heterocycles. In recent years, several

[3 + 2]-Cycloadditions of nitrile ylides after photoactivation of vinyl azides under flow conditions

• Stephan Cludius-Brandt,
• Lukas Kupracz and
• Andreas Kirschning

Beilstein J. Org. Chem. 2013, 9, 1745–1750, doi:10.3762/bjoc.9.201

• with thermal formation of 2H-azirines. Photochemically, the ring of the 2H-azirines was opened to yield the nitrile ylides, which underwent a [3 + 2]-cycloaddition with 1,3-dipolarophiles. When diisopropyl azodicarboxylate serves as the dipolarophile, 1,3,4-triazoles become directly accessible starting

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

• 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

• applications in numerous other areas of modern chemical sciences, such as bioconjugation [13], supramolecular chemistry, [14] and polymer sciences [15]. Probably the most useful and powerful procedure for the synthesis of 1,2,3-triazoles is the Huisgen 1,3-dipolar cycloaddition of organic azides with

A facile, rapid, one-pot regio/stereoselective synthesis of 2-iminothiazolidin-4-ones under solvent/scavenger-free conditions

• Murugan Sathishkumar,
• Sangaraiah Nagarajan,
• Poovan Shanmugavelan,
• Murugan Dinesh and
• Alagusundaram Ponnuswamy

Beilstein J. Org. Chem. 2013, 9, 689–697, doi:10.3762/bjoc.9.78

• -triazoles [25], 1,2,3-triazolylchalcones [26], and 1,2,3-triazolyldihydropyrimidine-2-thiones [27], we herein present a one-pot solvent/scavenger-free synthetic protocol for 2-iminothiazolidin-4-ones. This environmentally benign method avoids toxic organic solvents and acid scavengers, the details of which

Synthesis of 2,3-dihydronaphtho[2,3-d][1,3]thiazole-4,9-diones and 2,3-dihydroanthra[2,3-d][1,3]thiazole-4,11-diones and novel ring contraction and fusion reaction of 3H-spiro[1,3-thiazole-2,1'-cyclohexanes] into 2,3,4,5-tetrahydro-1H-carbazole-6,11-diones

• Lidia S. Konstantinova,
• Kirill A. Lysov,
• Ljudmila I. Souvorova and
• Oleg A. Rakitin

Beilstein J. Org. Chem. 2013, 9, 577–584, doi:10.3762/bjoc.9.62

• heterocycles (pyrrole [6][7], and triazoles [8]) were found to possess antifungal and antitumor activity toward a number of species causing fungal diseases and toward Walker 256 carcinoma cell lines. The compounds with the thiazoloanthroquinone structure have not been reported in the literature so far. We were

Microwave-assisted three-component domino reaction: Synthesis of indolodiazepinotriazoles

• Rajesh K. Arigela,
• Sudhir K. Sharma,
• Brijesh Kumar and
• Bijoy Kundu

Beilstein J. Org. Chem. 2013, 9, 401–405, doi:10.3762/bjoc.9.41

• ; indolodiazepinotriazoles; Introduction The intermolecular Huisgen azide–alkyne 1,3-dipolar cycloaddition reaction [1][2][3][4][5][6] for the synthesis of 1,2,3-triazoles in both aqueous [7][8][9][10] and organic solvents under either metal-catalyzed [11][12][13] or metal-free conditions [14][15][16] has received

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

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

• -economical syntheses of annulated 1,2,3-triazoles were accomplished through copper-catalyzed intramolecular direct arylations in sustainable one-pot reactions. Thus, catalyzed cascade reactions involving [3 + 2]-azide–alkyne cycloadditions (CuAAC) and C–H bond functionalizations provided direct access to

• fully substituted 1,2,3-triazoles with excellent chemo- and regioselectivities. Likewise, the optimized catalytic system proved applicable to the direct preparation of 1,2-diarylated azoles through a one-pot C–H/N–H arylation reaction. Keywords: cascade reaction; C–H functionalization; copper

• ; heteroarenes; triazoles; Introduction Transition-metal-catalyzed C–H bond functionalizations are increasingly viable tools for step-economical syntheses of various valuable bioactive compounds [1][2][3], which avoid the preparation and use of preactivated substrates [4][5][6][7][8][9][10][11][12][13][14][15

A quantitative approach to nucleophilic organocatalysis

• Herbert Mayr,
• Sami Lakhdar,
• Biplab Maji and
• Armin R. Ofial

Beilstein J. Org. Chem. 2012, 8, 1458–1478, doi:10.3762/bjoc.8.166

• adducts could only be isolated when the reaction mixtures containing 16 (for R2 = H) were worked up with dry K2CO3. Aqueous workup led to regeneration of the reactants. Vicario’s report that imidazoles, in contrast to triazoles and tetrazoles, do not readily undergo iminium activated additions to α,β

Parallel solid-phase synthesis of diaryltriazoles

• Matthias Wrobel,
• Jeffrey Aubé and
• Burkhard König

Beilstein J. Org. Chem. 2012, 8, 1027–1036, doi:10.3762/bjoc.8.115

• potential inhibitors of protein–protein interactions. Results and Discussion Synthesis of azide-functionalized Wang resins Two azide-functionalized resins were prepared for the solid-phase synthesis of diaryl-triazoles. The commercially available 4-(bromomethyl)benzoic acid (5) was converted into azide 6 in

• of regioisomers in reaction 3. Instead of the 1,4-disubstituted triazoles obtained from copper(I) catalysis, the complex pentamethylcyclopentadienylbis(triphenylphosphine)ruthenium(II) chloride leads to 1,5-disubstituted triazole compounds [19]. 4-(Azidomethyl)benzoic acid functionalized Wang resin 7

• -disubstituted triazoles due to a characteristic shift of the triazole proton resonance. The triazole proton of the 1,4-disubstituted ring in compound 11k shows a 1H NMR resonance at δ = 8.71 (400 MHz, DMSO-d6), while the resonance signal for the triazole proton of product 13f is observed at δ = 8.00 (400 MHz

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

• –donor type, in which thiophene moieties work as donor and 1,2,3-triazoles as acceptor units. In this respect, terminally ethynylated (oligo)thiophenes were coupled to halogenated (oligo)thiophenes in the presence of sodium azide and a copper catalyst. Optoelectronic properties of various thiophene-1,2,3

• high yield and purity. Click reactions generally involve a Cu(I)-catalyzed version of the Huisgen 1,3-dipolar cycloaddition of terminal acetylenes and azides (CuAAC), to regioselectively yield 1,4-disubstituted 1H-1,2,3-triazoles [11][12]. In the meanwhile, this type of click reaction has become very

• were investigated, in which thiophene units act as donors and triazoles as acceptors. As a general result we find that weak electronic conjugation through the 1,2,3-triazole ring is operative. Experimental General information All reactions were carried out under an inert atmosphere of argon. All

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

• )methyl]aziridines by Cu(I)-catalyzed azide-alkyne cycloaddition, followed by microwave-assisted, regioselective ring opening by dialkylamine towards 1-(2,3-diaminopropyl)-1,2,3-triazoles. Although most of these compounds exhibited weak antiplasmodial activity, six representatives showed moderate

• 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