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

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

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

• give the desired cyclopentane ring (23) [73]. The biological data of these compounds has yet to be reported. Wang et al. synthesized a series of pyridine and pyrimidine C-nucleosides (24–26) that mimic the riboside of favipiravir in their effort to develop novel anti-influenza compounds (Figure 10A

• exhibited potent activity against the H1N1 influenza strain (A/WSN/33) in cell based assays [74]. The pyrimidine compound 26 was synthesized using an identical approach and is not shown here. The activity of 24 and 25 as nucleosides was comparable to favipiravir and its riboside. Furthermore, they found

AuBr₃-catalyzed azidation of per-O-acetylated and per-O-benzoylated sugars

• Jayashree Rajput,
• Srinivas Hotha and
• Madhuri Vangala

Beilstein J. Org. Chem. 2018, 14, 682–687, doi:10.3762/bjoc.14.56

• purine and pyrimidine nucleoside synthesis using per-O-acyl/per-O-benzoyl furanosyl and pyranosyl o-hexynylbenzoates [23]. Subsequently, Hotha and co-workers utilized propargyl 1,2-orthoesters and alkynyl glycosyl carbonate donors for the synthesis of pyrimidine nucleosides [24][25]. In addition, N

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• the methyl group at the 5-position of the pyrimidine ring, shielded the leaving group-bearing phosphate from incoming water from some angles of attack. For OAt esters of ribonucleotides, we also measured the rates of hydrolysis at 0 °C and −20 °C, and the detailed data can be found in Supplementary

Recent advances on organic blue thermally activated delayed fluorescence (TADF) emitters for organic light-emitting diodes (OLEDs)

• Thanh-Tuân Bui,
• Fabrice Goubard,
• Malika Ibrahim-Ouali,
• Didier Gigmes and
• Frédéric Dumur

Beilstein J. Org. Chem. 2018, 14, 282–308, doi:10.3762/bjoc.14.18

• -TADF white OLEDs with 16% EQE could be fabricated [30]. 4. Triazine–pyrimidine based emitters Among possible electron acceptors, another structure has been extensively regarded as an adequate electron acceptor for the design of blue TADF emitters and this structure is the triazine unit. When combined

• -based devices is among the best so far reported for blue OLEDs. Attesting the interest of the community for this new acceptor, other authors developed quasi-simultaneously a structure–performance relationship with T24, T25 and T27–T28 (see Figure 8) [58]. The choice of pyrimidine as the electron

• acceptor was notably justified by authors due to the easier synthesis of the central core and a versatile peripheral substitution. Additionally, compared to triazine, the LUMO level of pyrimidine is slightly destabilized, facilitating the access to wide bandgap materials. In this work, a more intriguing

Fluorogenic PNA probes

• Tirayut Vilaivan

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

• pyrimidine rich sequences. Therefore, the performance of light-up probes is rather sequence-dependent, although it could be marginally improved by increasing the temperature. Rapid and specific detection of PCR products by light-up PNA probes in a simple mix-and-read fluorescence assay [160] or by real-time

• PCR [161][162] have been demonstrated in the context of pyrimidine rich sequences. A pair of pseudo-complementary PNA probes terminally labeled with TO allowed the detection of specific DNA sequences in long dsDNA and plasmids without requiring prior denaturation [163]. Although non-selective binding

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• enaminone intermediate 39 which underwent condensation and cyclization within C-4 of 5-aminopyrazole and the carbonyl group of the enaminone to generate pyrazolo[3,4-b]pyridine derivatives 40. However, the formation of pyrazolo[1,5-a]pyrimidine 41, a structural isomer of 40 was obtained when 1-NH-5

• -b]pyridine-spiroindolinone nucleus 59 with a high degree of regioselectivity without formation of the regioisomeric pyrazolo[1,5-a]pyrimidine 60 involving three-component reaction of 5-aminopyrazole 16, isatin 54 and cyclic β-diketones 58 in aqueous ethanol with p-TSA as catalyst (Scheme 13

• = tert-butyl) the reaction results in the formation of pyrazolo[1,5-a]pyrimidine derivative 90 as an additional product. The authors proposed that the bulky group had significantly slowed down the rate of electrophilic aromatic substitution at C-4 on 1H-pyrazol-5-amine due to which the aza-Michael

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

• probe BFdG, 3-MI, 2PyG, as well as the emissive RNA analogue thG [23][26][27][28]. Some notable pyrimidine analogues include our tricyclic analogues tC and tCO [29][30][31], pyrrolo-dC [32] and its derivatives [33] as well as thU, thC [23] and DMAC [34]. Apart from tC, tCO, qAN1 and thG, FBAs have not

• found to be general for a large set of 4-hydroxy-5-(o-aminoarylthio)pyrimidines [39]. The mechanism was thought to proceed via protonation of a pyrimidine ring nitrogen which activates it to nucleophilic attack by an unprotonated anilino nitrogen on the positive C4 of the pyrimidine ring which carries

• that consists of the 2-aminothieno[3,4-d]pyrimidine G-mimic deoxyribonucleoside (thdG) (see Figure 2) [23], developed by the Tor lab, as an energy donor and 1,3-diaza-2-oxophenothiazine (tC), developed by our lab, as an energy acceptor [57]. This G–C analogue FRET pair also displays the general

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• , pyrimidine, thiophene, etc. the Maiti group reported an alternative approach toward α-trifluoromethyl ketones starting from (hetero)arylacetylenes 7 and also aliphatic terminal alkynes 8 (Scheme 5) [24]. The trifluoromethyl radical was generated from CF3SO2Na as indicated earlier, oxygen from air was the

Metal-mediated base pairs in parallel-stranded DNA

• Jens Müller

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

• in the context of this review is the pyrimidine:purine:pyrimidine triplex, where each base triple formally comprises a regular Watson–Crick base pair and an additional pyrimidine residue hydrogen-bonded to the central purine moiety via its Hoogsteen edge. Conceptually, this Hoogsteen-bonded part of

• glycosidic bond conformations [46]. It needs to be noted that these correlations are derived from base pairs and triples comprising canonical purine and pyrimidine nucleobases only. In particular, it is assumed that both Hoogsteen and reversed Hoogsteen pairing involve the Hoogsteen edge of one purine

• residue and the Watson–Crick edge of the complementary pyrimidine or purine moiety. Artificial base pairs involving two purine entities facing each other via their respective Hoogsteen edge (vide infra, Scheme 8b) need to be treated differently, as this additional structural change leads to a change from

Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones

• Sergii V. Melnykov,
• Andrii S. Pataman,
• Yurii V. Dmytriv,
• Svitlana V. Shishkina,
• Mykhailo V. Vovk and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259

• preparation of acid 3 homologues (with a methylene linker between the carboxylic group and the pyrimidine ring) and their isomers resulting from two alternative regioselective pathways for the decarboxylative nucleophilic addition of malonic acid and its mono(thio)esters. Results and Discussion We first

• (1a) to substituted pyrimidones 2b–e carried out in the presence of TEA in toluene for 8 h has shown that a substituent at position 1 of the pyrimidine ring can significantly influence the progress of the reaction (Table 4). Thus, N1-alkyl-substituted compounds 2b–e exhibited a lower reactivity

• be increased by introduction of the ester functionality at position 5 as well as allyl, various benzyl or phenyl substituents at position 1 of the pyrimidine core. Notably, esters 6 and thioesters 8 are remarkable for their potential application as smooth amine acylating agents. It has been shown

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

• constants for the structure determinations of N-alkylated nitrogen-containing heterocycles in solution. This method was tested on the N-adamantylated products in a series of azolo-1,2,4-triazines and 1,2,4-triazolo[1,5-a]pyrimidine. The syntheses of adamantylated azolo-azines were based on the interactions

• -triazolo[1,5-a]pyrimidine [30], 1,2,4-triazolo[5,1-c][1,2,4]triazinone [31] and tetrazolo[1,5-b][1,2,4]triazinone [32] can be obtained by the fusion of an azine ring to an azole fragment. This method can be used for the selective incorporation of 15N atoms in different azolo-azines. Recently, we tested

• complicated the subsequent NMR analysis. Meanwhile, the application of [2,3-15N2]-5-aminotetrazole 7-15N2 provided the single double-labelled products in the tetrazolo[1,5-a]pyrimidine series [33]. Thus, in the current work, [2,3-15N2]-5-aminotetrazole 7-15N2 (98% enrichment for each of the labelled 15N atoms

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

• theory (DFT) for energetic and molecular orbital (MO) calculations. Keywords: 5-aminotetrazol; azide–tetrazole equilibrium; 2-azidopyrimidine; β-enaminones; tetrazolo[1,5-a]pyrimidine; trifluoromethylatedtetrazolo[1,5-a]pyrimidines; Introduction Tetrazolo[1,5-a]pyrimidines have attracted attention in

• using ultrasound irradiation promoted shorter reaction times, high regioselectivity, and excellent yields, when compared with conventional thermal heating [30]. Presently, we demonstrate an eco-friendly synthesis of 5- and 7-substituted tetrazolo[1,5-a]pyrimidine isomers, in good to excellent yields

• the β-enaminone precursor and (iii) elucidate the azide–tetrazole equilibrium when the compound is in solid form or dissolved in distinct solvents. The tetrazolo[1,5-a]pyrimidine synthesis was conducted from a cyclocondensation reaction of the type [CCC + NCN], in which the CCC block is a series of β

Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• demonstrate the regiochemistry of the reaction. These cascade reactions proceed first through a Michael addition of the primary amine on the enone, followed by an intramolecular cyclization by the pyridine/pyrimidine nucleus. Unfortunately, no crystal structure could be obtained for the imidazopyrimidines and

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• scale-up process, where the key reaction, a Zeigler coupling, of an early trifluoromethylimidazole intermediate 100 with commercially available 2-chloro-5-fluoropyrimidine afforded 101 (a compound with partially saturated pyrimidine framework). An aerobic oxidative dehydrogenation of 101 in the presence

• of molecular oxygen and with catalytic copper acetate (Cu(OAc)2) generated the desired pyrimidine 102 which was converted to the final products in a few more steps. This is one of the noteworthy examples where oxidative dehydrogenation has been utilized for the synthesis of a key intermediate of an

New electroactive asymmetrical chalcones and therefrom derived 2-amino- / 2-(1H-pyrrol-1-yl)pyrimidines, containing an N-[ω-(4-methoxyphenoxy)alkyl]carbazole fragment: synthesis, optical and electrochemical properties

• Daria G. Selivanova,
• Alexei A. Gorbunov,
• Olga A. Mayorova,
• Alexander N. Vasyanin,
• Igor V. Lunegov,
• Elena V. Shklyaeva and
• Georgii G. Abashev

Beilstein J. Org. Chem. 2017, 13, 1583–1595, doi:10.3762/bjoc.13.158

• ; electrochemical oxidation; pyrimidine; solvatochromism; Introduction Nowadays a great number of research projects concerning the synthesis of organic conjugated systems with a wide scope of their applications, primarily as materials for organic electronic devices such as light-emitting diodes, field-effect

• structure of side chains [10]. In this paper we describe a synthetic approach to some new D–π–A–D conjugated systems which include 9-[ω-(4-methoxyphenoxy)alkyl]carbazole as a donor fragment (D) and prop-2-enone and pyrimidine units as electron acceptor moieties (A). The optical and electrochemical

• linked with a central pyrimidine core and another one is linked by a rigid thiophene cycle as a π-conjugated bridge. We have applied a usual synthetic protocol which includes eight successive steps: O-alkylation of 4-methoxyphenol (1), N-alkylation of carbazole (2), formylation or acetylation of a

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

• synthesis of modified pyrimidine nucleosides using E. coli NPs [26]. 2.2 Synthetic strategies The classical protecting-group-free (pre-2000) synthetic strategies are dated back to well over 100 years with the discovery of the Fischer glycosylation (Scheme 6) [27][28]. Methanol can be glycosylated with D

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• convincing way [31]. Other coenzymes, possibly generated by such a swinging-arm thioester-dependent catalysis, may have been precursors of nucleotides, the essential building blocks of nucleic acids. As a matter of fact, extant biosynthesis of nucleotides (built on purine and pyrimidine carbon–nitrogen

• aromatic heterocycles) is based on the incorporation of amino acids in the core of nucleotide precursors. Pyrimidine nucleotide biosynthesis uses aspartate and combines together ubiquitous molecules, water, carbon dioxide, ammonium and phosphate (forming carbamoyl phosphate, also a precursor of arginine

Nucleophilic displacement reactions of 5′-derivatised nucleosides in a vibration ball mill

• Olga Eguaogie,
• Patrick F. Conlon,
• Francesco Ravalico,
• Jamie S. T. Sweet,
• Thomas B. Elder,
• Louis P. Conway,
• Marc E. Lennon,
• David R. W. Hodgson and
• Joseph S. Vyle

Beilstein J. Org. Chem. 2017, 13, 87–92, doi:10.3762/bjoc.13.11

• reactions require the use of high-boiling, dipolar aprotic solvents and anionic nucleophiles under anhydrous conditions at elevated temperatures (up to 150 °C). Competing intramolecular cyclisation reactions between both purine and pyrimidine nucleobases and (especially) the 5′-position of the (deoxy

• were observed with IdT (1d) and IdG (1e) although maximal conversion of IdG was achieved within one hour in the absence of added liquid (the reaction was inhibited in the presence of DMF). During these studies, LAG of both purine and pyrimidine substrates in the presence of ethyl acetate or hexane was

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

• comparison with the natural pyrimidine nucleosides in order to understand the impact of such modifications as monomers or constituents of oligonucleotides [8][9][10][11][12][13][14]. Thioxopyrimidine nucleosides as such, as well as building blocks of artificial oligonucleotides demonstrate promising

• antiviral activity in various experiments [15][16][17][18][19][20][21][22]. Regarding the chemical synthesis of this class of pyrimidine nucleosides various approaches were published (see, e.g., [8][9][10][11][14][15][16][23][24]; reviewed by Vorbrüggen and Ruh-Pohlenz [25]). On the contrary, only few

• 2.4.2.4) phosphorylases [36], and (ii) the role of structural features and electronic properties of the pyrimidine bases and nucleosides in the recognition by E. coli nucleoside phosphorylases. Results and Discussion Thioxo- and 6-aza-pyrimidines used in the transglycosylation reaction with recombinant E

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• dihydropyridine, hydantoin, imidazole, indole, isoquinoline, isoxazole, oxazole, 4H-pyran, pyrazine, pyridazine, pyridine, pyridinone, pyrimidine, pyrimidone, pyrrole, 3H-quinazolin-4-one, quinoline, 1H-quinolin-4-one, and thiophene. For heterocycles that are composed of a fused aromatic ring, such as

Methylpalladium complexes with pyrimidine-functionalized N-heterocyclic carbene ligands

• Dirk Meyer and
• Thomas Strassner

Beilstein J. Org. Chem. 2016, 12, 1557–1565, doi:10.3762/bjoc.12.150

• Dirk Meyer Thomas Strassner Physikalische Organische Chemie, TU Dresden, Bergstraße 66, 01062 Dresden, Germany 10.3762/bjoc.12.150 Abstract A series of methylpalladium(II) complexes with pyrimidine-NHC ligands carrying different aryl- and alkyl substituents R ([((pym)^(NHC-R))PdII(CH3)X] with X

• -NHC ligand [33]. To study the differences between both systems we synthesized palladium [34] and platinum [35] “hybrid complexes” with ligands combining both structural elements the pyrimidine as well as the NHC fragment. We also used density functional theory (DFT) calculations to investigate the

• different donor character. The experimentally determined geometrical parameters are in good agreement with the computed results. Interestingly, complexes 9, 10 and 12 show only one discrete doublet for the m-pyrimidine proton signals in the 1H NMR spectrum in DMSO-d6 indicating that the pyrimidine ring

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• alkoxyallene [46][47]. As mentioned above β-ketoenamide 3i is a good precursor for 2,2´-bipyridine derivative 4i, but Scheme 4 also reveals that this intermediate could be converted into the expected pyrimidine derivative 7 by treatment with ammonium acetate [48][49][50] or into pyrimidine N-oxide 8 by

• methoxylation of compound 3a we unexpectedly observed the formation of the 5-acetyl-substituted oxazole derivative 6. However, precursor 3i was smoothly available from acetylacetone 1a. It could smoothly be transformed into the desired bipyridine derivative 4i, but also into the related pyrimidine and

• pyrimidine N-oxide derivatives 7 and 8. Altogether, we could confirm that our approach to functionalized pyridine derivatives by cyclocondensation of β-ketoenamides is also a very versatile and flexible method for the synthesis of unsymmetrically substituted bipyridine derivatives or related heterocyclic

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• -metathesis of a challenging homoallylic urea substrate, which proceeds in good yields in the presence of an organic phosphoric acid. Keywords: cross-metathesis; natural products; pyrimidines; Tsuji–Trost reaction; synthetic methods; Introduction Chiral pyrimidine motifs constitute prevalent structural

• allylic substitution reaction of a joint precursor 5. Subsequently this strategy is successfully applied to the synthesis of the authentic pyrimidine cores 3 and 4 of manzacidin A (1) and ent-manzacidin C (2). Results and Discussion General synthetic concept As part of our ongoing efforts to the design of