A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

• Greta Utecht-Jarzyńska,
• Karolina Nagła,
• Grzegorz Mlostoń,
• Heinz Heimgartner,
• Marcin Palusiak and
• Marcin Jasiński

Beilstein J. Org. Chem. 2021, 17, 1509–1517, doi:10.3762/bjoc.17.108

• reported in the 1960s [17]. The latter 1,3-dipole was generated thermally from the respective tetrazole derivative 3, and the observed [3 + 2]-cycloadditions occurred chemoselectively to provide fused pyrazoles of the type 4 as exclusive products (Scheme 1). This type of cycloaddition attracted

• , generated from tetrazole 3, reported by Huisgen et al. [17]. Selected applications of trifluoroacetonitrile imines 7 in the synthesis of S-containing 5- and 6-membered heterocycles. Synthesis of [3 + 2]-cycloadducts 9a–l derived from CF3-substituted nitrile imines 7a–h and 1,4-quinones 1a and 1b. Thermal

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• the catalyst expense. As enantioselective catalysts require expensive structural modifications, the possibility of immobilisation would facilitate catalyst recovery/recycle and drastically reduce the cost of the associated process. In 2012, silica-supported 5-(pyrrolidin-2-yl)tetrazole 63 was used to

• ), column robustness/ease of recyclability and the facile nature of reaction condition and substrate screening. To increase the greenness and reduce the consumption of the catalyst, Yamamoto and Nakashima have recently developed a proline tetrazole 51 packed-bed reactor system, exploiting the low solubility

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• )-modified oligonucleotides was first described in 1991 by the Caruthers group [84]. Typically, each 2'-deoxynucleoside 3'-phosphorothioamidite is prepared by phosphitylating the protected nucleosides with tris(pyrrolidino)phosphine under tetrazole catalysis, followed by immediate treatment with

Synthesis and properties of oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing adenine, guanine, or 5-methylcytosine nucleobases

• Naohiro Horie,
• Takao Yamaguchi,
• Shinji Kumagai and
• Satoshi Obika

Beilstein J. Org. Chem. 2021, 17, 622–629, doi:10.3762/bjoc.17.54

• the middle position of 12-mer oligonucleotides (Table 1). The oligonucleotide synthesis was performed using an automated DNA synthesizer following the established synthetic method for GuNA[Me]-T-modified oligonucleotides [20]. 5-(Ethylthio)-1H-tetrazole (ETT) was used as an activator for the coupling

Mesoionic tetrazolium-5-aminides: Synthesis, molecular and crystal structures, UV–vis spectra, and DFT calculations

• Vladislav A. Budevich,
• Sergei V. Voitekhovich,
• Alexander V. Zuraev,
• Vadim E. Matulis,
• Vitaly E. Matulis,
• Alexander S. Lyakhov,
• Ludmila S. Ivashkevich and
• Oleg A. Ivashkevich

Beilstein J. Org. Chem. 2021, 17, 385–395, doi:10.3762/bjoc.17.34

• -(methylsulfonyl)-1-phenyl-1H-tetrazole with substitution of bromine and methylsulfonyl groups giving the corresponding tetrazolium salts or conjugate aminides. The obtained mesoionic tetrazoles have been characterized by elemental analysis, FTIR, NMR, and UV–vis spectroscopy, TGA/DSC analysis and for 1,3-di-tert

• : aminotetrazoles; DFT; mesoionic compounds; UV–vis spectra; X-ray analysis; Introduction 5-Aminotetrazoles are one of the most available and valuable tetrazole derivatives. So, due to the thermal stability and high nitrogen content the parent 5-aminotetrazole (1, Figure 1) is of practical interest as a gas

• -generator and blowing agent [1][2]. Moreover, it is a useful building block in organic synthesis, including various multicomponent reactions opening the way to diverse fused heterocycles [3]. Salts with anionic tetrazole, i.e., aminotetrazolates 2, and cationic ones, i.e., aminotetrazolium salts 3, are

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• Michal M. Wieclaw Bartlomiej Furman Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224, Warsaw, Poland 10.3762/bjoc.17.12 Abstract Herein we present the direct asymmetric synthesis of tetrazole-functionalized 1-deoxynojirimycin derivatives from simple sugars via a

• products. Finally, some surprising observations regarding the mechanism of their formation were made. Keywords: amide functionalization; iminosugars; Schwartz’s reagent; tetrazole; Introduction The transformation of an amide into another chemical moiety in a controlled manner is not a trivial task

• molecule incorporating both an iminosugar and a tetrazole fragment is of particular interest, due to the interesting properties of both moieties (Figure 1). It is probably hard to overestimate the importance of sugar scaffolds in nature, and we believe that it speaks for itself, however, a significance of

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• investigations on their more stable analogs resulted in the synthesis of stable 1-O-phoshono-β-ᴅ-psicofuranosyl sulfone, which was prepared by a simultaneous phosphorylation and oxidation of ethyl 2-thio-β-ᴅ-psicofuranoside with dibenzyl N,N-dimethylphosphoramidite catalyzed by 1H-tetrazole and followed by

• -fructofuranose derivatives 1 and started from the four known alcohols 4α, 5α, 5β and 6α [17]. Initial treatment of these alcohols with commercially available dibenzyl N,N-dimethylphosphoramidite as phosphorylating agent catalyzed by 1H-tetrazole and followed by direct oxidation with an excess of 3

• by GlfT2. Reagents and conditions: a) 1. (BnO)2P-NMe2, 1H-tetrazole, 0 °C→rt, 1 h, 2. m-CPBA, 0 °C→rt, 1.5‒2 h; b) H2, 10% Pd/C, MeOH, rt, 3‒4 h. Reagents and conditions: a) PivCl, pyridine, CH2Cl2, rt, overnight; b) BnBr, NaOH, TBAB, THF, reflux, 3 h. Reagents and conditions: a) EtSH, BF3∙OEt2

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

• t-BuOOH, and finally, the protecting groups were removed under basic conditions to give either MPC-1 or MPC-2 as ammonium salts. ETT = 5-(ethylthio)-1H-tetrazole. Preparation of mannosyl phosphoramidites. Starting from 2,3,4,6-tetra-O-acetyl-β-ᴅ-mannopyranose (β-4Ac-Man), the phosphitylation using 2

Microwave-assisted efficient one-pot synthesis of N²-(tetrazol-5-yl)-6-aryl/heteroaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines

• Moustafa Sherief Moustafa,
• Ramadan Ahmed Mekheimer,
• Saleh Mohammed Al-Mousawi,
• Mohamed Abd-Elmonem,
• Hesham El-Zorba,
• Afaf Mohamed Abdel Hameed,
• Tahany Mahmoud Mohamed and
• Kamal Usef Sadek

Beilstein J. Org. Chem. 2020, 16, 1706–1712, doi:10.3762/bjoc.16.142

• developed by reacting 5-amino-1,2,3,4-tetrazole with aromatic aldehydes and cyanamide in pyridine under controlled microwave heating with high yields. X-ray crystallography confirmed the structure of the obtained products. Keywords: microwave irradiation; N2-(tetrazol-5-yl)-6-aryl/heteroaryl-1,3,5-triazine

• ]. Tetrazole derivatives are a potent class of heterocyclic compounds with a wide range of biological activities owing to their unique structure. They play an important role not only as a bioisostere of the carboxylic acid group but also as flexible ligands which easily adopt to different binding modes [12][13

• ]. Tetrazole derivatives exhibit a wide spectrum of biological activities as antibacterial [14], anticancer [15], anti-inflammatory [16], antidiabetic [17], antitubercular [18], and analgesic [19] agents. It is well established that many medical disorders can be caused as a result of defects at more than one

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

• with thiol moieties such as phenylmercapto and phenylmercapto-tetrazole substituents resulted in Φf of 7% (compare 64–68) and 3% (compare 78), respectively. Thus, one can roughly draw the following order for the decrease fluorescence quantum yields located at the meso-position: PhO-; Ph- ≥ barbiturate

• ≥ Ph2N- > PhS- > phenylmercapto tetrazole. Thus, it would be difficult to draw conclusions based on these substituents with respect to their electronic properties. While Ph-O, Ph2N-, and Ph-S- exhibit electron donating properties, barbiturate and phenyl substituents can be seen more or less as electron

Diversity-oriented synthesis of spirothiazolidinediones and their biological evaluation

• Sambasivarao Kotha,
• Gaddamedi Sreevani,
• Lilya U. Dzhemileva,
• Milyausha M. Yunusbaeva,
• Usein M. Dzhemilev and
• Vladimir A. D’yakonov

Beilstein J. Org. Chem. 2019, 15, 2774–2781, doi:10.3762/bjoc.15.269

• tetrazolium dye, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (МТТ) or yellow tetrazole, to give insoluble formazan, which develops purple color particularly in living cells. Thus, the color gradient can serve to determine the degree of cytostatic activity (shift from proliferation to

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• rhodium(III)-catalyzed intermolecular annulation has been established for the preparation of tetrazole-isoquinolone/pyridone hybrids. Several N-acylaminomethyltetrazoles were reacted with arylacetylenes to form the hybrid products in moderate to very good yields. The method relies on the capacity of the

• rhodium catalyst to promote C(sp2)–H activation in the presence of a suitable directing group. The Ugi-azide reaction provides broad molecular diversity and enables the introduction of the tetrazole moiety, which may further assist the catalytic reaction by coordinating the metal center. The scope of the

• . Keywords: C–H activation; cyclization; isoquinolone; multicomponent reaction; tetrazole; Introduction Pyridones and isoquinolones are relevant heterocyclic scaffolds present in numerous bioactive compounds and natural products [1][2][3][4]. Similarly, molecules containing a tetrazole ring exhibit a wide

In water multicomponent synthesis of low-molecular-mass 4,7-dihydrotetrazolo[1,5-a]pyrimidines

• Irina G. Tkachenko,
• Sergey A. Komykhov,
• Vladimir I. Musatov,
• Svitlana V. Shishkina,
• Viktoriya V. Dyakonenko,
• Vladimir N. Shvets,
• Mikhail V. Diachkov,
• Valentyn A. Chebanov and
• Sergey M. Desenko

Beilstein J. Org. Chem. 2019, 15, 2390–2397, doi:10.3762/bjoc.15.231

• -withdrawing properties of the tetrazole ring, which makes them useful for studying various theoretical issues, e.g., tautomerism [5], intramolecular transformations [6], etc. There are several approaches to the synthesis of 4,7-dihydrotetrazolo[1,5-a]pyrimidines. Two of them make use of 5-aminotetrazole as a

• accessible by variation of the binucleophilic component 1 (instead of 1, 3-amino-1,2,4-triazole, 2-aminobenzimidazole, 3-aminopyrazoles, 4-amino-1,2,3-triazoles, etc. can be used [13]). However, a relatively low reactivity of amine 1 due to the electron deficiency of the tetrazole ring has been reported

• several times [5][6]. A third approach (Scheme 1, reaction 3) is completely different and consists of the tetrazole ring formation through cyclization of dihydropyrimidinethiones with sodium azide [14]. Generally, all three approaches allow for the preparation of a broad range of compounds 3 with a wide

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

Electrophilic oligodeoxynucleotide synthesis using dM-Dmoc for amino protection

• Shahien Shahsavari,
• Dhananjani N. A. M. Eriyagama,
• Bhaskar Halami,
• Vagarshak Begoyan,
• Marina Tanasova,
• Jinsen Chen and
• Shiyue Fang

Beilstein J. Org. Chem. 2019, 15, 1116–1128, doi:10.3762/bjoc.15.108

• -(ethylthio)-1H-tetrazole as activator instead of the typically used acetic anhydride. Oxidation was performed under standard conditions. The last nucleotide at the 5'-end of ODN was incorporated with a 5'-trityl nucleoside phosphoramidite instead of a 5'-DMTr counterpart. At the end of the synthesis, the 5

• × 2; coupling, phosphoramidite (0.1 M, MeCN), 5-(ethylthio)-1H-tetrazole (0.25 M, MeCN), 60 s × 3 (or 2); capping, 25 (0.1 M, MeCN) and 5-(ethylthio)-1H-tetrazole (0.25 M, MeCN), 60 s × 3; oxidation, I2 (0.02 M, THF/pyridine/H2O, 70/20/10, v/v/v), 40 s. For incorporating the last nucleoside monomer, a

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• of polystyrene resin 3 as the amine component. After resin removal with piperidine in DMF, a combinatorial strategy of replacing the carboxylic acid component with trimethylsilyl azide (TMSN3) (azido-Ugi reaction) or cyanic acid, followed by Fmoc removal (TFA), allowed the formation of the tetrazole

• tetrazole-ketopiperazines (Scheme 3). The strategy involved three steps: first, an Ugi tetrazole reaction between isocyanoacetate derivatives 8, tritylamine (9), various aldehydes and TMSN3, followed by treatment of the products with aqueous HCl, which cleaved both the trityl group and the methyl ester, to

• yield amino acids 11 bearing a 1,5-disubstituted tetrazole. The practicality of the Ugi tetrazole reaction (also called Ugi-azide or azido-Ugi reaction) has been recently reviewed [20][21]. These compounds were then used in an intramolecular three-component four-center Ugi reaction using equimolar

Synthesis and fluorescent properties of N(9)-alkylated 2-amino-6-triazolylpurines and 7-deazapurines

• Andrejs Šišuļins,
• Jonas Bucevičius,
• Yu-Ting Tseng,
• Irina Novosjolova,
• Kaspars Traskovskis,
• Ērika Bizdēna,
• Huan-Tsung Chang,
• Sigitas Tumkevičius and
• Māris Turks

Beilstein J. Org. Chem. 2019, 15, 474–489, doi:10.3762/bjoc.15.41

• equilibrium was studied in different deuterated solvents by 1H NMR spectroscopy on the example of 6-azido-9-heptyl-2-piperidinopurine 6b. Experiments were performed in CDCl3, THF-d8, CD3CN and DMSO-d6. The 1H NMR spectrum in CD3CN showed the presence of the tetrazole form and has been used for NMR studies in

• stability [39]. Regarding the tautomerism in 2,6-diazido-substituted starting materials, it has been studied previously for both purine [41] and 7-deazapurine [52] derivatives. In both cases practically only the diazido forms are observed in chloroform solution, but the proportion of the tetrazole tautomer

• wavelengths at 420 nm (Semrock, Rochester, NY, USA). Examples of fluorescent purine/7-deazapurine derivatives. 1H NMR spectra of compound 6b in CD3CN at different temperatures (300 MHz, c = 12.5 mg/mL); a, b, c – signals for azide form 6b-A; α, β, γ – signals for tetrazole form 6b-T). Comparison of 1H NMR

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• -transfer difference NMR (STD-NMR) led to the identification of thirty fragments. Subsequent 2D-15N–1H HSQC NMR returned four fragment hits 28–31 (Figure 7), with binding affinities, determined by NMR titration, in the low millimolar range. Of all of the fragments, tetrazole 31 was chosen for further

• optimization due to its physicochemical properties and its potential for fragment growth. After virtual screening and binding studies by STD-NMR studies, the authors were able to find tetrazole 32 (Figure 7) which had a three-fold improved affinity (Kd = 1.3 mM) compared to the initial hit 31. Later, the ZINC

• database [82] was searched for structurally similar compounds leading to the identification of the meta-substituted tetrazole 33 (Figure 7), which was found to have a similar dissociation constant. Moreover, in order to predict the orientation of the fragments in the binding site, molecular docking of 33

Artificial bioconjugates with naturally occurring linkages: the use of phosphodiester

• Takao Shoji,
• Hiroki Fukutomi,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 1946–1955, doi:10.3762/bjoc.14.169

• ]. The supported trinucleotide 1 was prepared from the support in 83% yield over 8 steps (Scheme S1, Supporting Information File 1) and used as a model in combination with 5-(benzylmercapto)-1H-tetrazole (BMT) as an activator (Table 1). The reaction was found to be rather sensitive to the concentration

• , entry 4). When the activator was switched to tetrazole, the yield was slightly decreased (Table 1, entry 5), while dicyanoimidazole (DCI) was proven to be an inefficient option for the reaction (Table 1, entry 6). It should be noted that the 5’-activated supported trinucleotide 2 was stable throughout

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• free NH group possess a low enough pKa to allow Mitsunobu coupling. In the course of the synthesis of the hexasaccharidic fragment of landomycin A, the L-rhodinose derivative 121 underwent glycosylation with 1H-tetrazole to give 122, which has a pKa that compares to carboxylic acids (Scheme 24) [89

• iminoglycosylphthalimide 115 from 114 [85]. Mitsunobu reaction as a key step in the total synthesis of aurantoside G [87]. Utilization of an N–H acid in the Mitsunobu reaction [88]. Mitsunobu reaction with 1H-tetrazole [89]. Formation of a rebeccamycin analogue using the Mitsunobu reaction [101]. Synthesis of

Recent advances in phosphorescent platinum complexes for organic light-emitting diodes

• Cristina Cebrián and
• Matteo Mauro

Beilstein J. Org. Chem. 2018, 14, 1459–1481, doi:10.3762/bjoc.14.124

Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry

• Katharina Hiebler,
• Georg J. Lichtenegger,
• Manuel C. Maier,
• Eun Sung Park,
• Renie Gonzales-Groom,
• Bernard P. Binks and
• Heidrun Gruber-Woelfler

Beilstein J. Org. Chem. 2018, 14, 648–658, doi:10.3762/bjoc.14.52

• donating as well as electron withdrawing functional groups, as coupling partners (Scheme 1). Concerning the targeted synthesis of 1, aryl halide 4e was of special interest as the cyano group is known to be convertible to the ortho-tetrazole moiety [9] present in the API. Based on prior optimisation studies

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• agents and readily undergoes β-elimination [27]. An alternative reagent is 2-cyanoethyl-N,N,N′,N′-tetraisopropylphosphordiamidite in combination with tetrazole derivatives such as benzylmercaptotetrazole. Under those conditions, the phosphitylation proceeds with the production of one equivalent of

• diisopropylamine, which is neutralized by benzylmercaptotetrazole released back after the reaction. The tetrazole derivative is sufficiently acidic to act as a scavenger for diisopropylamine converting it into the ammonium salt. Thus, fully protected trimers can be converted to phosphoramidites without the loss of

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• -diethylaminophosphepane (N,N-diethyl-1,5-dihydro-2,3,4-benzodioxaphosphepin-3-amine) in the presence of 1H-tetrazole followed by in situ oxidation with m-chloroperoxybenzoic acid (m-CPBA) to give fully protected 4’-phosphate 2. The azido group in 2 was reduced, the resulting amine was converted to the N-Fmoc carbamate

• in AcOH which reductively cleaved the N-Troc group (Scheme 3). After N-acylation by (R)-3 acyloxyacyl fatty acid and hydrolytic cleavage of 4’,6’-O-benzylidene acetal group with 90% aqueous TFA, the liberated 6’-hydroxy group was regioselectively protected as TBDMS ether to furnish 20. 1H-Tetrazole

• deprotection by catalytic hydrogenation furnished lipid A 31. Alternatively, the lactol 30 was phosphitylated by application of the phosphoramidite procedure with (benzyloxy)[(N-Cbz-3-aminopropyl)oxy](N,N-diisopropylamino)phosphine in the presence of 1H-tetrazole and subsequent oxidation with dimethyldioxirane