Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

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

• translation in in vitro translation experiments. In a further step, tetraphosphates with methylene(bisphosphonate) moieties were prepared which improved binding to eIF4E and in some cases conferred enzymatic resistance against DcpS degradation [67]. N2-Triazole-containing monophosphate cap analogues were

• modified methylguanosine resulting in a capped RNA containing a triazole linkage after CuAAC reaction (Figure 7B) [121]. In a similar approach a 5′-azido-modified RNA was prepared by solid-phase synthesis and reacted with an alkyne-functionalized m7G-cap analogue in a CuAAC reaction [122]. Besides its

• utility on long RNA, this click chemistry approach was also applied to the chemical synthesis of cap analogues, simplifying the typically laborious and time-consuming synthesis [121]. A plethora of cap analogues was synthesized replacing one phosphate bridge with a triazole linkage. Depending on their

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• reaction of 4-amino-5-alkyl-2,4-dihydro-1,2,4-triazole-3-thione with DAAD and triphenylphosphine was reported by Mosslemin et al. [25]. The reaction of triphenylphosphine with DAAD and triazole as the NH-acid and a precursor of the ambident sulfur nucleophile gave the corresponding vinylphosphonium salt 83

• . Generation of resonance-stabilized phosphorus ylides in the reaction of triphenylphosphine, dialkyl acetylenedicarboxylates, and 1,2,4-triazole-3-thione derivatives. Synthesis of resonance-stabilized phosphorus ylides via the reaction of triphenylphosphine with dialkyl acetylenedicarboxylates and 2

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• reacted easily in a SN2 reaction to give a more functionalized molecule. For example, treatment of the chlorinated monofluoroalkene with NaN3 provided the corresponding N3-containing monofluoroalkene. The azide group underwent a 1,3-dipolar cycloaddition to give a 1,2,3-triazole, which is also a peptide

¹⁵N-Labelling and structure determination of adamantylated azolo-azines in solution

• Sergey L. Deev,
• Alexander S. Paramonov,
• Tatyana S. Shestakova,
• Igor A. Khalymbadzha,
• Oleg N. Chupakhin,
• Julia O. Subbotina,
• Oleg S. Eltsov,
• Pavel A. Slepukhin,
• Vladimir L. Rusinov,
• Alexander S. Arseniev and
• Zakhar O. Shenkarev

Beilstein J. Org. Chem. 2017, 13, 2535–2548, doi:10.3762/bjoc.13.250

• product structure were also found for N-arylation or N-alkylation with tert-butyl fragments in the series of 1,2,3-triazole [15][16], tetrazole [17][18][19][20], and purine [21] derivatives. Meanwhile, knowledge of the accurate chemical structures of N-substituted heterocycles is essential for biomedical

• the most efficient way to measure JHN couplings [24]. Previously, the incorporation of a single 15N label in position 1 of the 1,2,4-triazole fragment of compounds 5 and 6 and analysis of the JCN couplings permitted the unambiguous identification of the structures of the N3-adamantylated derivatives

• by the reisomerization of the initially formed N2-adamantylated product (15a-15N2). Indeed, 2 h of refluxing of isolated 15a-15N2 in TFA with 1.5 molar equivalents of 14 yielded a mixture of compounds 15a-15N2 and 15b-15N2 in the same (1:2) ratio (Scheme 1). The use of [1-15N]-3-amino-1,2,4-triazole

A permutation approach to the assignment of the configuration to diastereomeric tetrads by comparison of experimental and ab initio calculated differences in NMR data

• Przemysław J. Boratyński

Beilstein J. Org. Chem. 2017, 13, 2478–2485, doi:10.3762/bjoc.13.245

• 1 and 2 were obtained by epimerization at C9. Mixtures of the isomers of 1 were formed in TBAF desilylation of Cinchona 4-TMS-triazole derivatives. Partial isomerisation of 2a into 2b was performed by transient deprotonation using in situ generated sodium methylsulfinylmethylide (Scheme 1). Both

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• , Bielefeld University, Universitätsstraße 25, D-33615 Bielefeld, Germany 10.3762/bjoc.13.240 Abstract The amide moiety of peptides can be replaced for example by a triazole moiety, which is considered to be bioisosteric. Therefore, the carbonyl moiety of an amino acid has to be replaced by an alkyne in

• N-sulfinylimines, which leads to amines with the same configuration as the proteinogenic (S)-configured amino acids. This stereoselection was confirmed by various X-ray crystal structures of propargylamines obtained during our investigations like 7a, 7c–e, 7s, 7i–k, 7q and triazole 13w (see

• sulfinamide (S)-1 into N-sulfinylimine 5w, which was reacted with (trimethylsilyl)ethynyllithium. However, following the usual procedure GP-4 with warming up the reaction mixture to room temperature before quenching with water led to the formation of triazole 13w, which was isolated in 56% yield (Table 4

Synthesis, effect of substituents on the regiochemistry and equilibrium studies of tetrazolo[1,5-a]pyrimidine/2-azidopyrimidines

• Elisandra Scapin,
• Paulo R. S. Salbego,
• Caroline R. Bender,
• Alexandre R. Meyer,
• Anderson B. Pagliari,
• Tainára Orlando,
• Geórgia C. Zimmer,
• Clarissa P. Frizzo,
• Helio G. Bonacorso,
• Nilo Zanatta and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 2396–2407, doi:10.3762/bjoc.13.237

• atom of the enone, both soft sites of the starting materials [29]. In recent research, we developed an efficient method to obtain 1,2,4-triazolo[1,5-a]pyrimidines from the cyclocondensation reaction of 1,1,1-trifluoro-4-metoxy-3-alken-2-one or β-enaminones with 5-amino-1,2,4-triazole. The methodology

• reactions were planned between phenylacetylene and compounds 6a–c. The 1,2,3-triazole synthesis from the 1,3-dipolar cycloaddition reaction between 6a–c and terminal alkynes catalyzed by copper salts (CuAAC) [41][42][43] confirms that the reaction passes through an azide intermediate. In addition to mild

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

• reactions using Cu(II), Cu(I) and Cu(0) catalysts have been successfully implemented to provide novel 6-phenyl-2-(trifluoromethyl)quinolines with a phenyl-1,2,3-triazole moiety at O-4 of the quinoline core. Milling procedures proved to be significantly more efficient than the corresponding solution

• synthesis of 5–8 Based on the recently obtained 1,2,3-triazole-appended N-heterocycles, as promising lead compounds with efficient and selective cytostatic activities [8][9], our research groups share an interest in derivatization of target compounds by a triazole bridge [33]. Quinoline is an important

• containing a trifluoromethyl group at C-2 and a p-halogen-substituted and non-substituted phenyl-1,2,3-triazole moieties. The synthesis of 2-(trifluoromethyl)-6-phenylquinolone was achieved by Conrad–Limpach reaction of a primary aromatic amine with a β-ketoester [37][38]. Namely, thermal condensation of 4

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

• aggregation can be suppressed due to strong repulsion by the introduction of a trifluoroethoxy group into the flexible binuclear phthalocyanine, which always adopts an open clamshell conformation. Binuclear phthalocyanines connected via a flexible triazole linker that are substituted by a tert-butyl (11) [81

• spectra of 9 (A) and 5 (B). Structure of binuclear phthalocyanines linked by a triazole linker. Structure of trinuclear phthalocyanines linked by a triazole linker, and windmill-like molecular structure vs aggregated structure. Direction of energy transfer of phthalocyanine–fullerene conjugates. Structure

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

• , disaccharide 48 was obtained with complete β-selectivity when the ortho-xylyl group (15-membered ring) was used, versus α/β = 1:3 selectivity in the case of the meta-xylene linked counterpart [80]. As in the previous example with the xylylene-derived linker, the triazole linker was removed under standard

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

• triazole moiety (Scheme 37a) using benzyl halides, sodium azide and a terminal alkyne via an alumina-supported copper catalyst. Using 10 mol % of Cu/Al2O3, differently substituted phenyl acetylenes and aliphatic alkynes led to 70–96% yield of triazoles [152]. Phenyl boronic acids were also used to

• 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

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

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

Effect of uridine protecting groups on the diastereoselectivity of uridine-derived aldehyde 5’-alkynylation

• Raja Ben Othman,
• Mickaël J. Fer,
• Laurent Le Corre,
• Sandrine Calvet-Vitale and
• Christine Gravier-Pelletier

Beilstein J. Org. Chem. 2017, 13, 1533–1541, doi:10.3762/bjoc.13.153

• devoted to the synthesis of new MraY inhibitors [49][50], we were interested in developing a more efficient access to 5’-ethynyluridine, a crucial building block for the further synthesis of triazole-containing compounds [49]. Intrigued by the moderate diastereomeric ratio reported for the addition or

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• pyridine and 2,6-lutidine using 1-(mesitylene-2-sulfonyl)-3-nitro-1,2,4-triazole (MSNT; 6 equiv) as an activator and N-methylimidazole (NMI; 10 equiv) as a nucleophilic catalyst. Each coupling was followed by precipitation/recrystallization from EtOH, capping with Ac2O in pyridine and precipitation from

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

• , 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

• , Himachal Pradesh, 176 061, India 10.3762/bjoc.13.110 Abstract An efficient, eco-compatible diversity-oriented synthesis (DOS) approach for the generation of library of sugar embedded macrocyclic compounds with various ring size containing 1,2,3-triazole has been developed. This concise strategy involves

• attached through Cu-catalyzed azide–alkyne cycloaddition (CuAAC) reaction (couple phase). Noteworthy, herein we utilized the CuAAC reaction as a medium for coupling different building blocks assembled iteratively to generate a 1,2,3-triazole moiety. This 1,2,3-triazole moiety linked as a spacer due to its

• 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

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• sometimes similar to 3-amino-1,2,4-triazole that was described as a component of GBB-3CR earlier [71][72][73][74][75]. Therefore, the first type of aminoazoles studied in our work was 5-amino-N-aryl-1H-pyrazole-4-carboxamide that showed 1,3-binucleophile properties in the condensation with aromatic

Synthesis of ribavirin 2’-Me-C-nucleoside analogues

• Fanny Cosson,
• Aline Faroux,
• Jean-Pierre Baltaze,
• Jonathan Farjon,
• Régis Guillot,
• Jacques Uziel and
• Nadège Lubin-Germain

Beilstein J. Org. Chem. 2017, 13, 755–761, doi:10.3762/bjoc.13.74

• carbon atom in the 2’-position are an indium-mediated alkynylation and a 1,3-dipolar cyclization. Keywords: alkynylation; antiviral; cancer; C-nucleosides; ribavirin; Introduction The triazole nucleoside ribavirin (RBV, Figure 1) is used for the treatment of a number of viral infections and may be

• catalytic hydrogenolysis. The latter reaction simultaneously cleaves the benzyl and isopropylidene groups affording compound 2 as a single isomer [22]. In the case of 5-(2’-deoxy-2’-methyl-2’-fluoro-β-D-ribosyl)-1,2,3-triazole-4-carboxamide (3) the synthesis was more delicate as it is necessary to

• procedures for compounds 2, 5–7, and 10–18 are covered by the Ph.D. thesis of Fanny Cosson [22]. 5-(2’-C-Methyl-β-D-ribofuranosyl)-1,2,3-triazole-4-carboxamide (2) [22]: Through the solution of compound 7 (mixture of 7a and 7b, 0.49 g, 1.1 mmol) in anhydrous methanol (14 mL) was bubbled ammonia gas for 2 h

Ultrasound-promoted organocatalytic enamine–azide [3 + 2] cycloaddition reactions for the synthesis of ((arylselanyl)phenyl-1H-1,2,3-triazol-4-yl)ketones

• Gabriel P. Costa,
• Natália Seus,
• Juliano A. Roehrs,
• Raquel G. Jacob,
• Ricardo F. Schumacher,
• Thiago Barcellos,
• Rafael Luque and
• Diego Alves

Beilstein J. Org. Chem. 2017, 13, 694–702, doi:10.3762/bjoc.13.68

• have been used for this cycloaddition reaction [20][21][22][23][24][25][26][27][28][29]. Organocatalytic approaches based on β-enamine–azide or enolate–azide cycloadditions have been employed to synthesize 1,2,3-triazole scaffolds [30][31][32]. Depending on the organocatalyst employed, different

• -(phenylselanylmethyl)-1,2,3-triazole A (Se-TZ) demonstrated an antidepressant-like effect (Figure 1) [60]. In another example, 5-phenyl-1-(2-(phenylselanyl)phenyl)-1H-1,2,3-triazole-4-carbonitrile B (Se-TZCN) was reported to exhibit antioxidant activities in different in vitro assays (Figure 1) [36]. Selenanyl-quinone

• found to be amenable to a range of 1,3-diketones or aryl azidophenyl selenides, providing an efficient access to novel selenium-containing 1,2,3-triazole compounds in good to excellent yields, in a few minutes of reaction at room temperature. The protocol was extended to activated ketones and

Derivatives of the triaminoguanidinium ion, 5. Acylation of triaminoguanidines leading to symmetrical tris(acylamino)guanidines and mesoionic 1,2,4-triazolium-3-aminides

• Jan Szabo,
• Julian Greiner and
• Gerhard Maas

Beilstein J. Org. Chem. 2017, 13, 579–588, doi:10.3762/bjoc.13.57

• heating yield 3-hydrazinyl-4-amino-4H-1,2,4-triazole hydrochloride (I, R = H) (Scheme 1) [13]. With the higher homologs of formic acid, the authors of that study observed the formation of resinous materials only. In a recent paper, however, evidence for the formation of the corresponding derivatives of I

• effectively with 3,4,5-trimethoxybenzoyl chloride (2b) to form the N,N’,N’’-tris(acylamino)guanidinium chloride 3 (Scheme 2). Hydrolysis of the acyl chloride is not a competitive reaction under these conditions, and formation of a 1,2,4-triazole, as observed for the reaction of 1 with formic acid at reflux

• crystal structure of salt 8b (Figure 2) shows a nearly planar core of the molecule (the triazole ring, N4, N5, N6). One face of this core is occupied by the three benzylic substituents, leaving the other face open for the chloride anion which is held in place by two N–H···Cl hydrogen bonds, one of them

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• carbene is an outstanding protocol for the synthesis of polyhydroxylated spiro- or fused 1-indanones [49]. Thus, the imidazole-based carbene catalyzed the conversion of phthalaldehydes 72 to dihydroxyspiro[indane-2,1′-isobenzofuran]-3-ones 73, whereas triazole-based carbene catalyzed the conversion of 72

Synthesis and optical properties of new 5'-aryl-substituted 2,5-bis(3-decyl-2,2'-bithiophen-5-yl)-1,3,4-oxadiazoles

• Anastasia S. Kostyuchenko,
• Tatyana Yu. Zheleznova,
• Anton J. Stasyuk,
• Aleksandra Kurowska,
• Wojciech Domagala,
• Adam Pron and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2017, 13, 313–322, doi:10.3762/bjoc.13.34

• enables the preparation of linear D–A–D compounds with one or two 1,3,4-oxadiazole [16][17][18][19], 1,3,4-thiadiazole [16][18][19][20][21][22] or 1,2,4-triazole [16][18] central rings symmetrically disubstituted with alkylbithiophene 1, 2 as well as star-shaped molecules with D–A arms 3 (Figure 1) [23

Versatile synthesis of end-reactive polyrotaxanes applicable to fabrication of supramolecular biomaterials

• Atsushi Tamura,
• Asato Tonegawa,
• Yoshinori Arisaka and
• Nobuhiko Yui

Beilstein J. Org. Chem. 2016, 12, 2883–2892, doi:10.3762/bjoc.12.287

• (Scheme 2). After 60 min of reaction, 1H NMR spectra of the obtained products (5a–c) were measured (Figure 3A). In the 1H NMR spectra of 5a and 5b, the protons assignable to 1,2,3-triazole linkages are observed at 8.5 and 9.4 ppm, respectively, which were consistent with the previous report [28]. These

• , triazole). The same reaction was performed for 4b and 4c according to the above described procedure. Synthesis of water-soluble benzylazide group-terminated PRX (6) To solubilize 4a into an aqueous solutions, 2-(2-hydroxyethoxy)ethyl (HEE) groups were modified onto the threading α-CDs of 4a [28][29

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• with halides (Ka ≈ 103–104 M−1 in acetone-d6). Not surprisingly, a higher number of hydrogen bonds with an anion correlated with the higher stability of the receptor/anion complex. 1,2,3-Triazole-based catalysts for the dearomatization of N-heteroarenes The Mancheno group recently explored triazole

• designed and synthesized various chiral triazole-based complexes such as L2–L4 (Scheme 2) [36][37][38][39]. It was proposed that while these triazole derivatives are conformationally flexible, upon their binding to halogen anions these complexes adopt a reinforced chiral helical conformation. The resultant

• 1,2,3-triazole, ammonium and pyridinium based catalysts. While the asymmetric transformations catalyzed by chiral 1,2,3-triazoles are now well precedented, the feasibility of asymmetric transformations promoted by other types of chiral C–H hydrogen bond donors is yet to be demonstrated. Similarly