DABCO- and DBU-promoted one-pot reaction of N-sulfonyl ketimines with Morita–Baylis–Hillman carbonates: a sequential approach to (2-hydroxyaryl)nicotinate derivatives

• Soumitra Guin,
• Raman Gupta,
• Debashis Majee and
• Sampak Samanta

Beilstein J. Org. Chem. 2018, 14, 2771–2778, doi:10.3762/bjoc.14.254

• products [4], medicines [5], chelating agents in transition metal complexes [6][7], and material science [8][9]. Pyridine derivatives such as vitamins B6, B3 (niacin), and nicotinamide adenine dinucleotide (NAD) play a significant role in the metabolism process of living organisms. Consequently, many

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• anthraniloyl-AMP. The reason why the fluorinated anthraniloyl-AMP shows good affinity is the formation of a hydrogen bond of the fluorine with the G279 backbone amide hydrogen and furthermore an interaction with the N7 position of the adenine moiety. Additionally a very typical fluorine/main-chain interaction

Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

• Vladimir A. Burilov,
• Guzaliya A. Fatikhova,
• Mariya N. Dokuchaeva,
• Ramil I. Nugmanov,
• Diana A. Mironova,
• Pavel V. Dorovatovskii,
• Victor N. Khrustalev,
• Svetlana E. Solovieva and
• Igor S. Antipin

Beilstein J. Org. Chem. 2018, 14, 1980–1993, doi:10.3762/bjoc.14.173

• attention to the synthesis of host molecules with high affinity to biologically important anions [1][2][3][4][5]. Among these anions, nucleotide recognition and sensing represents an especially important research area due to the great biological significance of these anions. Adenine-containing nucleotides

• interactions between the adenine groups of the nucleotide and the receptor’s aromatic moieties [9] can additionally contribute to the complex stability and binding selectivity. Polyammoniums mimic the biologically important acyclic polyamines such as putrescine, spermidine, and spermine, which have strong

• the recognition and sensing based on the principle of competitive EY displacement by adenine-containing nucleotides. The incorporation of 10b into a polydiacetylene matrix allowed to create covalently bonded vesicles for the selective detection of ADP. Experimental Material and methods All reagents

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• MGBs is their preference for narrow A·T-rich regions compared to G·C regions because (i) they can form hydrogen bonds to N3 of adenine and O2 of thymine in the A·T region; (ii) less steric hindrance in the A·T region in comparison to the G·C region due to the presence of an extra protruding C2-amino

• a broad spectrum of in vitro and in vivo antitumor activities. Tallimustine retains the preference for A·T-rich regions in the minor groove that alkylates N3 of adenine in a highly sequence specific manner, thereby inhibiting the binding of transcription factors such as OTF-1 and NFE1 on specific AT

• activities were evaluated [102]. A molecular docking study has revealed that GRA interacts with ct-DNAs via hydrogen bonding interactions between the oxygen atoms of GRA and adenine bases of DNA and van der Waals interactions. Moreover, GRA significantly reduces the polymerization activity of DNA polymerase

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• latter reaction rapidly decomposed during work-up in solution. Regioselective and stereoselective glycosidation of adenine, N6-benzoyladenine, N4-benzoylcytosine, thymine and uracil to the corresponding β-N9-purine or β-N1-pyrimidine ribosides was achieved on gram scales under Vorbrüggen-type conditions

• adenosine-5′-monophosphoromorpholidate with the sodium salts of 5′-phosphorylated nucleosides without any predrying and in the presence of acidic promoters and water gave complete reaction within 90 minutes (Scheme 13) [53]. In this original report, the preparation of nicotinamide adenine dinucleotide (NAD

• contain both adenine and thymine derivatives. The specificity of the Ade–Thy hydrogen bonding was not disrupted in the presence of non-interacting bases. Tsiourvas and co-workers obtained a similar result after grinding an equimolar mixture of the hexadecylammonium salts of a succinylated acyclovir

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• containing uracil or guanine base were cleaved exceptionally fast [82]. No mechanistic explanation was given. Interestingly, these two bases may undergo deprotonation under mildly basic conditions (pKa ≈ 9) in contrast to adenine and cytosine. Aliphatic amines are poor catalysts for the cleavage of RNA. The

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• -Me analogues of pyrrolo- and imidazo[2,1-f][1,2,4]triazine C-nucleosides using a 2'-β-Me lactone that mimic adenosine and guanosine (12–19, Figure 8) [71][72]. The adenine analogues of pyrrolo- and imidazo[2,1-f][1,2,4]triazine were active as nucleosides in HCV1b RNA replication assays, and as

An uracil-linked hydroxyflavone probe for the recognition of ATP

• Márton Bojtár,
• Péter Zoltán Janzsó-Berend,
• Dávid Mester,
• Dóra Hessz,
• Mihály Kállay,
• Miklós Kubinyi and
• István Bitter

Beilstein J. Org. Chem. 2018, 14, 747–755, doi:10.3762/bjoc.14.63

• recognition sites [16][18][19][33], or Zn-dipicolylamine complexes [21][23][24] attracting the negatively charged phosphate units of ATP and by π-stacking between the fluorophores of the sensors and the adenine moiety of ATP [29]. In aqueous solutions at physiological pH, the tetra-charged anionic ATP

• consists of a hydrophilic (phosphate and ribose) and a more hydrophobic part (adenine). The former ensures a good solubility of ATP in water and generates an electrostatic field around it while the latter is required for associations with similar planar hydrophobic molecules involved in the biochemical

• way to enhance the selectivity. Since ATP has one adenine nucleobase, a simple uracil/thymine unit appended to a neutral chemosensor operating mainly through π-interaction could be a good model for investigation. We selected DMHF as the fluorophore and core scaffold because of its easy synthesis and

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• light-up behavior was also observed with the fluorescent nucleobase 9-(pyrenylethynyl)adenine when incorporated in acpcPNA, but not in DNA [200]. In the case of DNA–DNA duplexes, the nucleobase most likely adopts a syn conformation, thereby placing the hydrophobic pyrene moiety in the base stack at the

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• complemented with among others the adenine analogue FRET pair, qAN1–qAnitro, increasing the flexibility of the methodology. Here we present the design, synthesis, photophysical characterization and use of such base analogues. They enable a higher control of the FRET orientation factor, κ2, have a different

• conjugation. As an effect of the need for hydrogen bonding properties, size restriction and sterical effects these demands are often conflicting [15][18][19]. However, there is an increasing number of exceptions to this and since the pioneering work of Ward et al. on adenine analogues [20] a whole range of

• small modifications to nucleobases, such as the 8-vinyldeoxyadenosine [21], has led to the introduction of fluorescence. Considering the differences in the structures of purines and pyrimidines, adenine is unique amongst the natural bases as it offers several sites for modifications: C2, C8, the C6

Metal-mediated base pairs in parallel-stranded DNA

• Jens Müller

Beilstein J. Org. Chem. 2017, 13, 2671–2681, doi:10.3762/bjoc.13.265

• adenine which was shown to bind transition metal ions better than its parent nucleobase [74]. Accordingly, its propensity to engage in metal-mediated base pairing was investigated in detail. As it turned out, εA is capable of simultaneously binding two metal ions with an almost parallel alignment of the N

Pyrene–nucleobase conjugates: synthesis, oligonucleotide binding and confocal bioimaging studies

• Artur Jabłoński,
• Yannic Fritz,
• Hans-Achim Wagenknecht,
• Rafał Czerwieniec,
• Tytus Bernaś,
• Damian Trzybiński,
• Krzysztof Woźniak and
• Konrad Kowalski

Beilstein J. Org. Chem. 2017, 13, 2521–2534, doi:10.3762/bjoc.13.249

• Chemistry, Biological and Chemical Research Centre, University of Warsaw, Żwirki and Wigury 101, 02-089 Warszawa, Poland 10.3762/bjoc.13.249 Abstract Fluorescent pyrene–linker–nucleobase (nucleobase = thymine, adenine) conjugates with carbonyl and hydroxy functionalities in the linker were synthesized and

• solution. In respect to the complementary oligothymidine T10 template in water, compounds 3 and 5 both show a self-assembling behavior according to canonical base–base pairing. However, in buffer solution, derivative 5 was much more effective than 3 in binding to the T10 template. Furthermore the adenine

• mechanism of sensing involves Hg(II) ion coordination to two thymine moieties followed by pyrene excimer formation [19]. Furthermore, compound A2 and adenine derivative A3 were reported to act as fluorescent sensors for thymine and adenine [23]. To the best of our knowledge, pyrene–nucleobases have not been

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• is illustrated by the recent works reporting the reaction of bis(diethylamino)chlorophosphine (95) with the acetal 96 in the presence of a Lewis acid to yield the phosphonodiamide 97. Then the nucleophilic addition of adenine and the hydrolysis of the phosphonodiamide function in phosphonic acid

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

First total synthesis of kipukasin A

• Chuang Li,
• Haixin Ding,
• Zhizhong Ruan,
• Yirong Zhou and
• Qiang Xiao

Beilstein J. Org. Chem. 2017, 13, 855–862, doi:10.3762/bjoc.13.86

• number of antiviral and antitumor drugs [3][4]. On the other hand, naturally occurring nucleosides, especially marine nucleosides, have also played an indispensable role in drug discovery, which make great contribution in the commercialization of cytosine arabinoside (Ara-C), adenine arabinoside (Ara-A

Investigation of the action of poly(ADP-ribose)-synthesising enzymes on NAD⁺ analogues

• Sarah Wallrodt,
• Edward L. Simpson and
• Andreas Marx

Beilstein J. Org. Chem. 2017, 13, 495–501, doi:10.3762/bjoc.13.49

• introducing small, terminal alkyne functionalities at common sites of the adenine base. Upon successful incorporation into PAR, these alkynes serve as handles for copper(I) catalysed azide–alkyne click reaction (CuAAC) [22] with fluorescent dyes. Terminal alkynes are the smallest possible reporter group that

• . Conclusion In this paper, we investigated the scope of PAR synthesising enzymes, namely ARTD1, ARTD2, ARTD5 or ARTD6 for using modified NAD+ analogues. It was found that NAD+ analogues 1 and 2 modified with alkyne groups in adenine position 2 and 6 are used by all these enzymes to a certain extent, whereas

• the employed substitutions in adenine at position 7 and 8 completely abrogated the processing towards PAR. The DNA-dependent ARTDs ARTD1 and ARTD2 can process 2-modified analogues best as also sterically demanding compounds such as dye-modified 5 are processed. Thus, 2-modified analogues are the best

Revaluation of biomass-derived furfuryl alcohol derivatives for the synthesis of carbocyclic nucleoside phosphonate analogues

• Bemba Sidi Mohamed,
• Christian Périgaud and
• Christophe Mathé

Beilstein J. Org. Chem. 2017, 13, 251–256, doi:10.3762/bjoc.13.28

• carbocyclic nucleoside methylphosphonate analogues bearing purine bases (adenine and guanine) was accomplished using bio-sourced furfuryl alcohol derivatives. All compounds were prepared using a Mitsunobu coupling between the heterocyclic base and an appropriate carbocyclic precursor. After deprotection, the

• nucleoside methylphosphonates (Figure 1) bearing purine bases (adenine and guanine) in order to evaluate their antiviral properties. Results and Discussion Synthesis of precursors (+/−)-5 and (+/−)-7 The synthesis began with the preparation of racemic 4-O-TBDMS-2-cyclopentenone (1) which was obtained in two

• -Boc-adenine or 2-amino-6-chloropurine in the presence of diisopropyl azodicarboxylate (DIAD) and PPh3, provided the N9 carbocyclic nucleosides (+/−)-8 and (+/−)-9 as racemic mixtures. No concomitant formation of the N7 regioisomer was observed. The removal of Boc and acetyl groups from (+/−)-8

Enzymatic synthesis and phosphorolysis of 4(2)-thioxo- and 6(5)-azapyrimidine nucleosides by E. coli nucleoside phosphorylases

• Vladimir A. Stepchenko,
• Anatoly I. Miroshnikov,
• Frank Seela and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2016, 12, 2588–2601, doi:10.3762/bjoc.12.254

• -thiouridine (very weak substrate) vs uridine (non-substrate), thymidine (very weak substrate) vs 2-thiothymidine (non-substrate). Shugar and co-workers studied the substrate properties of N-3-regioisomers of adenosine and inosine, N3-(β-D-ribofuranosyl)-adenine (N3-Ado) and -hypoxanthine (N3-Ino

• ). Structures of 2-thiopyrimidine(9–12) and 5-azacytidine (13 and 14) nucleosides. Energy minimized structures of N3-(β-D-ribofuranosyl)adenine (left) and 5-aza-2′-deoxycytidine (right) and in the mid both structures are overlapped by the glycosyl bonds (calculations by ab initio, 3-21G level; Polak–Ribiere

Facile synthesis of a 3-deazaadenosine phosphoramidite for RNA solid-phase synthesis

• Elisabeth Mairhofer,
• Elisabeth Fuchs and
• Ronald Micura

Beilstein J. Org. Chem. 2016, 12, 2556–2562, doi:10.3762/bjoc.12.250

• motives [1][2]. Selected adenines in their active sites have been discussed to participate in acid base catalysis, thereby contributing to accelerate the specific phosphodiester cleavage of these nucleolytic ribozymes. Concerning the twister ribozyme, structural analyses suggest that an adenine N3 atom

• plays a dominant role in catalysis [3][4][5]. Also for the pistol ribozyme, evidence exists that an adenine-N3 in the active site is significant for the cleavage activity, most likely by 5’-O-leaving group stabilization through proton shuttling [6][7]. Another example for a specific role of an adenine

• basicity of these purine nitrogen atoms, because N1 represents the major protonation site, followed by N7 and N3. This order is deduced from the macroscopic pKa values that were measured for adenine, 9-methyladenine, and adenosine [11]. Importantly, there is growing evidence that the pKa values of

DNA functionalization by dynamic chemistry

• Zeynep Kanlidere,
• Oleg Jochim,
• Marta Cal and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2016, 12, 2136–2144, doi:10.3762/bjoc.12.203

• product (Supporting Information File 1, Figure S1, Table S2). A reaction between GCHO and ON1 in the presence of TC was accomplished with complete conversion of ON1 into the guanine incorporated product (ON1+G). The reactions with cytosine (CCHO) as well as adenine (ACHO) aldehydes gave similar yields

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• and was verified by mutagenesis and kinetic studies. In the active site, Glu141 and His129 activate the C3 keto group by protonation. The pro-S hydride of the reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) is then transferred to the C3. The resulting hydroxy group participates in the

• any cofactors, in spite of its flavin adenine dinucleotide (FAD) binding site [98][99]. The reaction mechanisms and biosynthetic enzymes involved in the rearrangement of versicolorin B (106) to demethylsterigmatocystin (107) have also been discussed controversely. Up to four genes (aflM, aflN, aflX

Highly stable and reusable immobilized formate dehydrogenases: Promising biocatalysts for in situ regeneration of NADH

• Barış Binay,
• Dilek Alagöz,
• Deniz Yildirim,
• Ayhan Çelik and
• S. Seyhan Tükel

Beilstein J. Org. Chem. 2016, 12, 271–277, doi:10.3762/bjoc.12.29

• potential candidate for the immobilization of enzymes and the immobilized FDHs, especially FDHIALD, is a robust biocatalyst and it may be used in the combination with other dehydrogenases to regenerate NADH. Experimental Nicotinamide adenine dinucleotide hydrate (NAD+) was purchased from Acros Organics (New

A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• complexation and, indeed, multiple guests could be measured at once [14]. The HPLC method of determining complexation ΔΗ° values was extended by Vincent Kwan to hydrogen bonding host–guest complexes [15]. Molecular tweezers that complex adenine and analysis of binding interactions The idea of incorporating

• ]. The aromatic cleft of molecular tweezer 11 showed no affinity for adenine 8 and the carboxylic acid 10 bound 8 rather weakly (−ΔG° = 3.3 kcal/mol), yet the cleft and acid group cooperate together to give the very stable complex 8·9. One simple interpretation in line with Jencks’ idea is that the

• graduate student at Columbia University, which was quite close in structure to 4, synthesized and studied at Illinois. Chemically bonded stationary phase 5 used for HPLC assay of nitrated aromatics and for quantitative enthalpy determinations. Adenine 8 recognition by carboxylic acid containing tweezer 9

Synthesis of cyclic N¹-pentylinosine phosphate, a new structurally reduced cADPR analogue with calcium-mobilizing activity on PC12 cells

• Ahmed Mahal,
• Stefano D’Errico,
• Nicola Borbone,
• Brunella Pinto,
• Agnese Secondo,
• Valeria Costantino,
• Valentina Tedeschi,
• Giorgia Oliviero,
• Vincenzo Piccialli and
• Gennaro Piccialli

Beilstein J. Org. Chem. 2015, 11, 2689–2695, doi:10.3762/bjoc.11.289

• analogues of the cADPR in which the adenine base was replaced by a hypoxanthine ring [24]. This kind of modification produced the cyclic inosine diphosphate ribose (cIDPR) 2 which proved to be stable in hydrolytic physiological conditions and showed significant Ca2+ mobilizing activity, thus fostering the

Synthesis and evaluation of the biostability and cell compatibility of novel conjugates of nucleobase, peptidic epitope, and saccharide

• Dan Yuan,
• Xuewen Du,
• Junfeng Shi,
• Ning Zhou,
• Abdulgader Ahmed Baoum,
• Khalid Omar Al Footy,
• Khadija Omar Badahdah and
• Bing Xu

Beilstein J. Org. Chem. 2015, 11, 1352–1359, doi:10.3762/bjoc.11.145

• designed the nucleopeptides 5 and 6. In addition, we substituted thymine with adenine to generate nucleopeptides 7 and 8 that contain adenine, the nucleobase is complementary of thymine. Synthesis The NA conjugates 5–8 were obtained according to a facile method of solid-phase peptide synthesis (SPPS) [17

• nanostructure (Figure 1C). This result implies that the base pair interactions between thymine and adenine likely play a critical role for the hydrogelation of the mixture of 5 + 8. In addition, we did gelation tests for 4 + 5 and 4 + 7. Both mixtures are unable to self-assemble to form hydrogels at the same