Synthesis of nanodiamond derivatives carrying amino functions and quantification by a modified Kaiser test

• Gerald Jarre,
• Steffen Heyer,
• Elisabeth Memmel,
• Thomas Meinhardt and
• Anke Krueger

Beilstein J. Org. Chem. 2014, 10, 2729–2737, doi:10.3762/bjoc.10.288

• ]pyrimidine derivatives. For the quantification of primary amino groups a modified photometric assay based on the Kaiser test has been developed and validated for different types of aminated nanodiamond. The results correspond well to values obtained by thermogravimetry. The method represents an alternative

• the IR spectrum (Figure 2), namely the vibrations at 1590, 1530 and 1430 cm−1 are caused by the grafted heteroaromatic moieties. The spectrum corresponds well to the signals observed for 2,4-bis(methylthio)pyrimidine [17]. The surface loading was determined by TGA and elemental analysis based on the

• the sulfones (see spectra c) and d) in Figure 2). A control experiment using nanodiamond not functionalized with the pyrimidine proved the reactivity of surface groups of the nanodiamond (CH, OH, π-bonds etc. are present on thermally annealed nanodiamond [18]) with MCPBA showing the formation of

Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction

• László Tóth,
• Yan Fu,
• Hai Yan Zhang,
• Attila Mándi,
• Katalin E. Kövér,
• Tünde-Zita Illyés,
• Attila Kiss-Szikszai,
• Balázs Balogh,
• Tibor Kurtán,
• Sándor Antus and
• Péter Mátyus

Beilstein J. Org. Chem. 2014, 10, 2594–2602, doi:10.3762/bjoc.10.272

• -1',2'-dihydro-2H,7b'H,9'H-spiro[pyrimidine-5,8'-quinolino[1,2-d][1,4]benzoxazepine]-2,4,6(1H,3H)-trione (rac-trans-7a): To a stirred solution of rac-5 (100 mg, 0.27 mmol) in chloroform (5 mL), anhydrous MgSO4 (150 mg, 1.25 mmol) and 1,3-dimethylbarbituric acid (60 mg, 0.38 mmol) were added and the

Versatile synthesis of amino acid functionalized nucleosides via a domino carboxamidation reaction

• Vicky Gheerardijn,
• Jos Van den Begin and
• Annemieke Madder

Beilstein J. Org. Chem. 2014, 10, 2566–2572, doi:10.3762/bjoc.10.268

• using palladium-based coupling chemistry to the pyrimidine C5 or the 7-position of 7-deaza-2’-deoxyadenosine [38][39][40]. During enzymatic incorporation the extra functionalities do not need to be protected. However, solid phase DNA synthesis implies an appropriate protection of the extra

• of imidazole modified pyrimidine and purine derivatives for solid phase synthesis have been described to date [41][44][45][46][47], we believe that the reactions described here serve as an ideal model system, which can be extended to other commercially available amino acid derivatives and nucleosides

• of the pyrimidine double bond, transfer hydrogenation with cyclohexene as hydrogen source and 10% palladium on carbon should be used [60][61][62]. As the methyl ester derivative of the amino acid is commercially available but rather expensive, we performed the esterification reaction on the benzyl

Pyrrolidine nucleotide analogs with a tunable conformation

• Lenka Poštová Slavětínská,
• Dominik Rejman and
• Radek Pohl

Beilstein J. Org. Chem. 2014, 10, 1967–1980, doi:10.3762/bjoc.10.205

• analogs [12]. In this publication, we present a conformational analysis of pyrrolidine azanucleotide analogs 7–14 containing thymine and adenine as examples of pyrimidine and purine nucleobases, respectively (Figure 2), and show how the conformation is affected by the mode of the phosphonate moiety

Syntheses of ¹⁵N-labeled pre-queuosine nucleobase derivatives

• Jasmin Levic and
• Ronald Micura

Beilstein J. Org. Chem. 2014, 10, 1914–1918, doi:10.3762/bjoc.10.199

• . Keywords: heterocycles; ligands; nucleic acids; nucleobases; nucleosides; pyrrolopyrimidinones; Introduction The small pyrrolo[2,3-d]pyrimidine 7-(aminomethyl)-7-deazaguanine is a natural product, also termed prequeuosine base (preQ1 base) [1][2]. This guanine derivative is involved in the complex

• chromatography on SiO2 and isolated in good yields. The pyrrolo[2,3-d]pyrimidine ring system of preQ1 base was built in good yields via the cyclocondensation reaction between [15N1,15N3,H215N(C2)]-2,6-diaminopyrimidin-4-one (6) and the 2-bromo-3-phthalimidopropan-1-al (7). Finally, deprotection was performed

• pyrrolo[2,3-d]pyrimidine ring system is based on the cyclocondensation reaction between α-bromoaldehydes and 2,6-diaminopyrimidin-4-ones and utilizes [15N]-KCN, [15N]-phthalimide, and [15N3]-guanidine for 15N sources to achieve three complementary labeling patterns that cover all five nitrogen atoms of

Synthesis of a bifunctional cytidine derivative and its conjugation to RNA for in vitro selection of a cytidine deaminase ribozyme

• Nico Rublack and
• Sabine Müller

Beilstein J. Org. Chem. 2014, 10, 1906–1913, doi:10.3762/bjoc.10.198

• ',3'-bis-O-(tert-butyldimethylsilyl)-1-[4-(N'-biotinyl-3,6-dioxaoctane-1,8-diamine)pyrimidine-2(1H)-onyl]-β-D-riboside (12). I: 2.6 equiv ZnBr2, DCM, 1 d, rt, Ar, 82%; II: 1.1 equiv EDAC·HCl, 1.1 equiv biotin, DMF, 0 °C → rt, overnight, 65%; III: THF/TFA/H2O (4:1:1, v/v/v), 0 °C, 5 h, 94%. Formation

Structure/affinity studies in the bicyclo-DNA series: Synthesis and properties of oligonucleotides containing bc^en-T and iso-tricyclo-T nucleosides

• Branislav Dugovic,
• Michael Wagner and
• Christian J. Leumann

Beilstein J. Org. Chem. 2014, 10, 1840–1847, doi:10.3762/bjoc.10.194

• oligonucleotides under the conditions of measurement. The corresponding Tm-data are summarized in Table 2. The bcen-T modification destabilizes duplexes with complementary DNA by −1.4 to −2.0 °C per modification relative to dT in a somewhat sequence dependent context. If flanked by two pyrimidine nucleotides (ON1

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• a secondary amine (i.e., dimethylamine [49][50], diethylamine [51][52], N-methylbenzylamine [49], pyrrolidine [53][54], or piperidine [55][56]) at temperatures ranging from 60 °C to 100 °C afforded the corresponding 5-(alkylaminomethyl)pyrimidine nucleosides 2 (Scheme 2). Compounds 2 served as

• rather limited. Zhang et al. obtained a series of pyrimidine nucleoside-thazolidinone hybrids 15 from 5-formyl-3',5'-di-O-acetyl-2'-deoxyuridine (14), an arylamine and mercaptoacetic acid (Scheme 6) [65]. The reactions were performed in a ionic liquid ([bmim]PF6). Products 15 were obtained in good to

The chemoenzymatic synthesis of clofarabine and related 2′-deoxyfluoroarabinosyl nucleosides: the electronic and stereochemical factors determining substrate recognition by E. coli nucleoside phosphorylases

• Ilja V. Fateev,
• Konstantin V. Antonov,
• Irina D. Konstantinova,
• Tatyana I. Muravyova,
• Frank Seela,
• Roman S. Esipov,
• Anatoly I. Miroshnikov and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2014, 10, 1657–1669, doi:10.3762/bjoc.10.173

• ; Introduction Pyrimidine and purine 2-deoxy-2-fluoro-β-D-arabinofuranosides demonstrate a broad spectrum of biological activity [1][2][3][4][5][6][7][8][9] and are valuable constituents of artificial oligonucleotides of great molecular biological and medicinal potential [10][11]. Among this family of

• obtained in 29 and 39% yield, respectively [19]. Previously, we have applied the MacDonald method for the synthesis of α-D-arabinofuranose-1-phosphate (Ara-1P) and showed that it is a versatile substrate for the enzymatic synthesis of both purine and pyrimidine nucleosides [22][23]. In addition, we

• pyrimidine β-D-arabinofuranosides by using α-D-arabinofuranose-1-phosphate (Ara-1P) as the glycosylating agent and the respective recombinant E. coli nucleoside phosphorylases as biocatalysts [22][23]. It was thus shown that Ara-1P is a universal glycosylating substrate for the synthesis of both purine and

Pyrene-modified PNAs: Stacking interactions and selective excimer emission in PNA₂DNA triplexes

• Alex Manicardi,
• Lucia Guidi,
• Alice Ghidini and
• Roberto Corradini

Beilstein J. Org. Chem. 2014, 10, 1495–1503, doi:10.3762/bjoc.10.154

• sequence with prevalence of pyrimidine bases, complementary to cystic fibrosis W1282X point mutation were synthesized. These compounds showed sequence-selective switch-on of pyrene excimer emission in the presence of target DNA, due to PNA2DNA triplex formation, with stability depending on the number and

• recognition; triplex stabilization; Introduction Peptide nucleic acid (PNA) probes are very selective in the recognition of DNA and have been used in a large variety of diagnostic methods, easily allowing the detection of point mutations at very low concentrations [1][2][3]. Poly-pyrimidine PNA can form very

• homopyrimidine sequences since the presence of one or more purine residues destabilizes these complexes and favour the formation of less stable duplexes [8]. Therefore it would be of great value to adopt strategies for the stabilization of triplex structures even in the presence of non-pyrimidine bases. From the

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• ; stereoselective amine synthesis; triol synthesis; Introduction 7-Deazapurine (pyrrolo[2,3-d]pyrimidine) nucleosides are commonly found in nature playing a variety of roles such as building blocks of nucleic acids and tRNA, metabolites or antimetabolites [1]. Deazapurine ribonucleosides also show interesting

• , respectively [5][6]. In turn, the biosynthesis of PreQ0 originates from guanosine 5’-triphosphate (GTP, 4) [7] (Figure 1) and involves four steps via a tetrahydropterine intermediate. The pyrrolo[2,3-d]pyrimidine core is a privileged scaffold for the development of kinase inhibitors; an inspection of the

• to prepare diverse chiral amine building blocks and react them with a common halo-purine intermediate to obtain the desired final products. The pyrrolo[2,3-d]pyrimidine core of PreQ0 was furnished following a method described by Klepper et al. [13] (Figure 3). The two step process started with the

Synthesis, characterization and DNA interaction studies of new triptycene derivatives

• Sourav Chakraborty,
• Snehasish Mondal,
• Rina Kumari,
• Sourav Bhowmick,
• Prolay Das and
• Neeladri Das

Beilstein J. Org. Chem. 2014, 10, 1290–1298, doi:10.3762/bjoc.10.130

• generated when a purine (A/G) or a pyrimidine (C/T) base is stripped off from the DNA strand and this is considered as the most common type of DNA damage lesions. We generated one abasic site in a 48-base pair long oligomer duplex by treating the DNA (Figure 3) with Uracil DNA Glycosylase (UDG) enzyme

Use of activated enol ethers in the synthesis of pyrazoles: reactions with hydrazine and a study of pyrazole tautomerism

• Denisa Tarabová,
• Stanislava Šoralová,
• Martin Breza,
• Marek Fronc,
• Wolfgang Holzer and
• Viktor Milata

Beilstein J. Org. Chem. 2014, 10, 752–760, doi:10.3762/bjoc.10.70

• species, which are possible for ester compounds 5b and 5c are shown in Figure 3, with the last character of the label being an E indicates enol, O denotes oxo, and (Z,E) – HO vs OH/=O Compound 5b was previously prepared by a ring contraction of pyrimidine-2,4-dione [19]. It is known from the literature

• enol ether/hydrazine is 1:1, as in the case of the reaction with 3c, the formation of 7-aminopyrazolo[1,5-a]pyrimidine-3,6-dicarbonitrile could be expected as a byproduct [24][25]. When hydrazine hydrochloride is used [14], ethyl 3-ethoxypyrazole-4-carboxylate was obtained in 41% yield and the expected

The Flögel-three-component reaction with dicarboxylic acids – an approach to bis(β-alkoxy-β-ketoenamides) for the synthesis of complex pyridine and pyrimidine derivatives

• Mrinal K. Bera,
• Moisés Domínguez,
• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 394–404, doi:10.3762/bjoc.10.37

• dihydropyrimidinones or the corresponding dihydropyrimidinethiones. Due to their general importance (e.g. as biologically active compounds) the development of efficient protocols for the preparation of functionalized pyridine [10][11][12][13][14][15][16][17][18][19][20] and pyrimidine derivatives [21][22][23][24][25

• E- and Z-configured enamide moieties [51][52], finally leading to identical products. After these successful multicomponent reactions we investigated the intramolecular condensations of the bis(β-ketoenamides) 13–15 to pyridine and pyrimidine derivatives. Enamides 13 and 14 were treated with

• acetate in a sealed tube we obtained a 1:1 mixture of bis(pyrimidine) derivative 23a and pyrimidine 23b still containing one β-ketoenamide unit with an overall yield of 68%. However, full conversion of 13 into 23a was achieved by increasing the amount of ammonium acetate to 16 equiv and using a higher

Organobase-catalyzed three-component reactions for the synthesis of 4H-2-aminopyrans, condensed pyrans and polysubstituted benzenes

• Moustafa Sherief Moustafa,
• Saleh Mohammed Al-Mousawi,
• Maghraby Ali Selim,
• Ahmed Mohamed Mosallam and
• Mohamed Hilmy Elnagdi

Beilstein J. Org. Chem. 2014, 10, 141–149, doi:10.3762/bjoc.10.11

• the products. Finally, these compounds were used for the efficient synthesis of 6-amino-5-cyanonicotinic acid ester derivatives 31a,b, ethyl 4-amino-5H-pyrano[2,3-d]pyrimidine-6-carboxylates 33a,b, 4-amino-6H-pyrrolo[3,4-g]quinazoline-9-carbonitrile 39, and 1,7-diamino-6-(N'-hydroxycarbamimidoyl)-3

• acid derivatives 31a,b, ethyl 4-amino-5H-pyrano[2,3-d]pyrimidine-6-carboxylates 33a,b, 4-amino-6H-pyrrolo[3,4-g]quinazoline-9-carbonitrile 39, and 1,7-diamino-6-(N'-hydroxycarbamimidoyl)-3-oxo-5-phenyl-3H-isoindole-4-carboxylate 40. X-ray crystal structure of 9. X-ray crystal structure of 13a. X-ray

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

IBD-mediated oxidative cyclization of pyrimidinylhydrazones and concurrent Dimroth rearrangement: Synthesis of [1,2,4]triazolo[1,5-c]pyrimidine derivatives

• Caifei Tang,
• Zhiming Li and
• Quanrui Wang

Beilstein J. Org. Chem. 2013, 9, 2629–2634, doi:10.3762/bjoc.9.298

• Caifei Tang Zhiming Li Quanrui Wang Department of Chemistry, Fudan University, 200433 Shanghai, P. R. of China 10.3762/bjoc.9.298 Abstract Oxidative cyclization of 6-chloro-4-pyrimidinylhydrazones 4 with iodobenzene diacetate (IBD) in dichloromethane gives rise to [1,2,4]triazolo[4,3-c]pyrimidine

• pyrimidine moiety is an important pharmacophore [1]. Especially, the fused bi- or tricyclic heterocyles containing a pyrimidine motif have received considerable interest in the design and discovery of new compounds for pharmaceutical and herbicidal applications [2][3]. For example, the pyrrolo[2,3-d

• ]pyrimidine derivative, ruxolitinib (INCB018424), was discovered as a selective JAK1 and JAK2 inhibitor, which is currently under clinical investigation [4]. To date, a number of fused pyrimidine-type compounds have been successfully commercialized, such as the pyrazolo[3,4-d]pyrimidine allopurinol and the

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• , pyrimidine-derived analogues (1,3-diazines) are the most common. Pyridazines (1,2-diazines) and pyrazines (1,4-diazines) are less prominent. The main reasons are most probably that pyrimidines are highly abundant in important biogenic molecules such as the ribonucleotides and that this heterocycle can be

• readily obtained through well-established condensation chemistries. In the next sections the most common syntheses of a number of drugs containing the pyrimidine as well as pyridazine and pyrazine scaffolds are presented. Furthermore, some non-aromatic derivatives including bicyclic analogues of these

• structures will be introduced. The additional nitrogen atom in pyrimidine leads to a significantly reduced basicity when compared to simple pyridine (pKa[pyrimidine] = 1.1; pKa[pyridine] = 5.3) as well as a much more electron-deficient ring system. However, owing to the presence of two nitrogen atoms

Synthesis, characterization and luminescence studies of gold(I)–NHC amide complexes

• Adrián Gómez-Suárez,
• David J. Nelson,
• David G. Thompson,
• David B. Cordes,
• Duncan Graham,
• Alexandra M. Z. Slawin and
• Steven P. Nolan

Beilstein J. Org. Chem. 2013, 9, 2216–2223, doi:10.3762/bjoc.9.260

• ) with each (hetero)aromatic amine in THF at room temperature for 20 h. A range of aromatic amines were employed, including aniline, diphenylamine, pyridines, a pyrimidine and one isoquinoline. The corresponding complexes were obtained in analytically pure form and in good yields as yellow or white

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• and coworkers then applied the same strategy to prepare two other types of heterocycles, isoquino[2,1-a][3,1]oxazine and isoquino[2,1-a]pyrimidine (75, Scheme 19) [87]. The use of [Ir(ppy)2(dtbbpy)](PF6) with air as the external oxidant was found to be optimal for catalyzing the reaction. Later, the

One-step synthesis of pyridines and dihydropyridines in a continuous flow microwave reactor

• Mark C. Bagley,
• Vincenzo Fusillo,
• Robert L. Jenkins,
• M. Caterina Lubinu and
• Christopher Mason

Beilstein J. Org. Chem. 2013, 9, 1957–1968, doi:10.3762/bjoc.9.232

• favourably with microwave-heated batch experiments. For dihydropyrimidinone 8, a flow rate of 2 mL min–1 delivered a very respectable processing rate of 25 g h–1. Following the success of this reactor design in delivering pyridine and pyrimidine heterocycles, albeit from very different processes, and the

Damage of polyesters by the atmospheric free radical oxidant NO₃^•: a product study involving model systems

• Catrin Goeschen and
• Uta Wille

Beilstein J. Org. Chem. 2013, 9, 1907–1916, doi:10.3762/bjoc.9.225

• the strongest free-radical oxidants known [E(NO3•/NO3−) = 2.3–2.5 V vs NHE] [9], and recent product studies by us revealed that NO3• readily damages aromatic amino acids and pyrimidine nucleosides through an oxidative pathway [10][11][12][13]. Thus, the ease by which model compounds of biologically

Cyclization of substitued 2-(2-fluorophenylazo)azines to azino[1,2-c]benzo[d][1,2,4]triazinium derivatives

• Aleksandra Jankowiak,
• Emilia Obijalska and
• Piotr Kaszynski

Beilstein J. Org. Chem. 2013, 9, 1873–1880, doi:10.3762/bjoc.9.219

• with increasing number of fluorine atoms at the benzene ring. No triazinium ions were obtained from azo derivatives of 4-cyanopyridine, pyrazine and pyrimidine, presumably due to their instability under the reaction conditions. The experimental results and mechanism are discussed with the aid of DFT

• reactivity of the azines, and CH2OH to provide a potential synthetic handle for the incorporation into more complex structures. Here we present the synthesis of four substituted derivatives of 1a and investigate the preparation of cations derived from pyrazine 2 and pyrimidine 3 shown in Figure 2. Our

• the pyrazine derivative 5-Z (ΔG298 = 2.7 kcal/mol), which also has the lowest TS energy (ΔG‡298 = 18.7 kcal/mol, Table 2). On the other hand, the cyclization of pyrimidine 6-Z is most endergonic and has the highest TS energy among all azoazines considered in this work. These significant differences

The first example of the Fischer–Hepp type rearrangement in pyrimidines

• Inga Cikotiene,
• Mantas Jonusis and
• Virginija Jakubkiene

Beilstein J. Org. Chem. 2013, 9, 1819–1825, doi:10.3762/bjoc.9.212

• -pyrimidinediamines. It was found that the outcome of the reaction strongly depends on the structure of the pyrimidines. Activation of the pyrimidine ring by three groups with a positive mesomeric effect is crucial for the intramolecular nitroso group migration. Keywords: Fischer–Hepp rearrangement; nitrosation; 5

• -nitrosopyrimidines; nucleophilic substitution; pyrimidinediamines; Introduction The pyrimidine moiety is an important structural motif in natural products and therefore frequently used as a building block for pharmaceutical agents [1][2]. It is well-known that chemical properties of pyrimidines depend on the π

• -defficient character of this heterocycle. An electrophilic aromatic substitution at the C-5 of a pyrimidine is usually difficult [1][3][4][5]. However, the presence of two or three activating groups leads to the successful introduction of an electrophile (Scheme 1) [1][6][7][8]. On the other hand

An organocatalytic route to 2-heteroarylmethylene decorated N-arylpyrroles

• Alexandre Jean,
• Jérôme Blanchet,
• Jacques Rouden,
• Jacques Maddaluno and
• Michaël De Paolis

Beilstein J. Org. Chem. 2013, 9, 1480–1486, doi:10.3762/bjoc.9.168

• electronically deficient pyridyl residue was also converted into 5e (80%) while pyrrolidine 4f bearing a pyrazine core underwent aromatization with high efficiency to give 5f (97%). The C2-symmetric scaffold 4g was efficiently converted into 5g (86%) and similar treatment of pyrimidine 4h provided pyrrole 5h in

• heteroaryl substituents, with yields ranging from 64–87%. Oxidation under the same conditions was found to be more troublesome with pyrazine 5f since alcohol 9f was isolated in only 20% yield. Similar treatment of pyrazine 5g and pyrimidine 5h gave a complex mixture of products. While the oxidation of the