Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• react with oxidative agents, it was expected to form a cationic intermediate as in the case of allylsilanes described above. A direct coupling of glycals with nucleobases is challenging, since it is formally a C–N bond-forming reaction with cleaving of the inactive C–H bond at the γ-position. Actually

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• charged moieties attached to nucleobases or the ribose sugar. Some selected examples 1–6 of resulting nucleic acid structures are provided in Figure 2 [30][31][32][33][34][35][36][37]. Oligonucleotides of this type are at least partially zwitterionic, but overall densely charged. With respect to the

• nucleobases. Remarkably, neither cytidinyl nor 7-deazaguanyl DNG oligomers furnish triplexes, but bind their complementary DNA counterstrand in a 1:1 ratio [65][66]. Furthermore, it was shown that an increase in ionic strength shields the oppositely charged backbones, thus destabilizing both DNG-DNA duplexes

• modifications based on additionally attached positively charged moieties, but retaining an intact phosphate diester backbone (B1, B2 = nucleobases) [30][31][32][33][34][35][36][37]. Oligonucleotide analogues with artificial cationic backbone linkages discussed in this review: aminoalkylated phosphoramidates 7

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

• MBM. Synthesis of pyrophosphorothiolate-linked dinucleoside cap analogues in a MBM to effect hydrolytic desilylation and phosphate coupling. Co-crystal grinding of alkylated nucleobases in an amalgam mill (N.B. no frequency was recorded in the experimental description). Preparation of DNA-SWNT complex

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

• of the nucleobases at the terminus with the templating base were readily identified. Dissociation constants were determined by fitting the chemical shifts of terminal nucleotides in the 1H NMR, measured at different nucleotide concentrations. With the DNA hairpins and unactivated deoxynucleotides

• experimental data for either of the four nucleobases and the two different backbone chemistries. Figure 9a and 9b show representative plots of theoretical yields and data points from RNA-based assays at different monomer concentrations. It can be discerned that 7.2 mM monomer concentration does not suffice to

• magnetic beads (Figure 10) [32]. The assays allowed for near-quantitative incorporation of any of the four nucleobases opposite their complementary base in the template, but the reactions on the RNA-based system are quite slow. For aminoterminal DNA, a methodology was developed by us that allows repeated

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• is incompatible with the standard deprotection treatment under basic conditions (generally aqueous ammonia) used to cleave other common base-labile acyl protection groups from nucleobases and release ON from the solid support. Furthermore, as the aqueous solubility of fully modified SATE

• use of photolabile protecting groups [38] of allyloxycarbonyl groups deprotected by Pd(0) [39] and of fluoride-labile groups [40] in place of the standard acyl protection of nucleobases has made possible the acquisition of short sequences of heteropolymer pro-oligonucleotides. However, none of these

• phosphotriester groups on ribonucleic neutral (RNN) phosphoramidite building blocks containing 2’-modifications (2’-F, 2’-OMe) to avoid 2’-OH nucleophilic attack on the phosphotriester linkage. Moreover, they used extremely mild basic diisopropylamine in methanol to deprotect nucleobases containing phenoxyacetyl

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

• ]. A key issue in all these methodologies is that the 5'- or the 3'-O-protecting group is selectively cleaved, whereas all other protecting groups (at the nucleobases, the phosphorous and the 5'- or alternatively 3'-OH group) remain intact. Basically, this aim has been achieved, although in particular

• dimers and extension to the trimer in either 5'- or 3'-direction. Removal of the 3'-O-protecting group under conditions that leave all other protecting groups at 5'-OH, nucleobases and internucleotide phosphates intact. Release of trinucleotide blocks from the solid support by cleavage of an oxalyl

Fluorogenic PNA probes

• Tirayut Vilaivan

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

• discussed under the topic of PNA probes carrying fluorescent nucleobases (vide infra). Dual-labeled PNA molecular beacons have been extensively used on their own or in combination with fluorescence melting curve analyses for genotyping [71][72][73] and analyses of genetic mutations, including single

• interactions, it is mainly governed by hydrophobic interactions and hydrogen bonding between nucleobases and the GO surface [132]. Duplex DNA interacts less strongly with GO since the pairing nucleobases are buried inside the duplex in dsDNA. This phenomenon, together with the ability of GO to act as an

• base via a rigid linker that disfavors such intercalation [175][176]. PNA probes carrying fluorescent nucleobases There are three major strategies to introduce fluorescent nucleobases into oligonucleotides or PNA probes. These are (i) the extension of conjugation in the natural nucleobase, (ii

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

• 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

• pyrimidines, only the C5 and C6 positions are available for modifications without directly perturbing the base-pairing properties. The subtle differences between the nucleobases within a class could lead one to believe that the chemistry developed for modifications of adenine would translate easily to guanine

• stable compared to other common fluorescent base analogues [15][16]. The absorption maxima of tC and tCO in DNA are found at approximately 395 and 365 nm (Figure 3) [30][31], respectively, and, thus, are well separated from the absorption of the natural nucleobases. The emission of tC and tCO in duplex

Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial

• Tamara Šmidlehner,
• Ivo Piantanida and
• Gennaro Pescitelli

Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5

• adequately prepared and characterized. For that reason, a short description of the most important issues in sample preparation is summarized in chapters 2.2 and 2.3. 2.1. Relation between DNA or RNA secondary structure and polarization spectroscopy Nucleobases are achiral but nucleoside and nucleotide

Metal-mediated base pairs in parallel-stranded DNA

• Jens Müller

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

• metal-based functionality. In metal-mediated base pairs, the hydrogen bonds between complementary nucleobases are replaced by coordinate bonds to one or two transition metal ions located in the helical core. In recent years, the concept of metal-mediated base pairing has found a significant extension by

• metal-mediated base pair, the complementary nucleobases are pairing via coordinate bonds rather than hydrogen bonds (Figure 1). Metal-mediated base pairs can be obtained from natural nucleobases such as cytosine or thymine [5]. In addition, many artificial nucleobases have been developed for an

• 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

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

• compounds. The conjugates bearing a carbonyl function represent weak emitters as compared to compounds with a hydroxy function in the linker. The self-assembly properties of pyrene nucleobases were investigated in respect to their binding to single and double strand oligonucleotides in water and in buffer

• . Confocal microscopy confirmed that 5 predominantly stains mitochondria but it also accumulates in the nucleoli of the cells. Keywords: confocal microscopy; luminescence; nucleobases; oligonucleotide binding; pyrene; X-ray; Introduction Pyrene is a planar, polycyclic aromatic hydrocarbon which shows well

• 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

Chemical systems, chemical contiguity and the emergence of life

• Terrence P. Kee and
• Pierre-Alain Monnard

Beilstein J. Org. Chem. 2017, 13, 1551–1563, doi:10.3762/bjoc.13.155

• , and finally iv) systems could have conditioned the proliferation of functional systems. Chemical selection The investigation of synthetic pathways to biochemically relevant molecules has clearly underlined the need for some form of selection. Indeed, molecules of interest (nucleobases [57], sugars [58

• chemicals with fatty acid vesicles demonstrates that chemical systems, even simple ones, could have spawned such a selection by conditioning the interactions between their molecular constituents. For instance, canonical nucleobases interact more extensively with the vesicles structures than some of their

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

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

• the nucleobases are usually protected with acyl groups and the 5´-OH of the monomeric building block with a 4,4’-dimethoxytrityl group (DMTr), or sometimes with its monomethoxytrityl analog (MMTr) [4][5]. To achieve coupling, phosphoramidites are activated with azoles [6], such as tetrazole [7], its

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

• acceptor, with the product of the reaction termed glycoside. Examples of acceptor molecules in nature are other saccharides to form oligosaccharides, nucleobases to form nucleosides, and amino acid side chains to form glycoproteins. The donor is the electrophile in the reaction and, therefore, when

Conjecture and hypothesis: The importance of reality checks

• David Deamer

Beilstein J. Org. Chem. 2017, 13, 620–624, doi:10.3762/bjoc.13.60

• then become testable hypotheses. Here is a proposed list of conditions that seem to be essential prerequisites if cellular life is to originate in one of the two alternative conditions: There must be a source of organic compounds relevant to biological processes, such as amino acids, nucleobases

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

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

• nucleobases can be significantly shifted within a well-structured RNA fold [12][13][14][15]. To address RNA phenomena of that kind, comparative atomic mutagenesis is an indispensable means, and with respect to ribozymes, can deliver important insights into the RNA catalyzed chemical reactions and underlying

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

• oligonucleotides. The amino group containing phosphoramidite was used together with complementary single-strand DNA templates that influenced the Watson–Crick base-pairing equilibrium in the mixture with a set of aldehyde modified nucleobases. A significant fraction of all possible base-pair mismatches was

• presynthesized oligomers with abasic sites on the backbone for the addition of individual monomeric nucleobases and consider the synthesis of new oligonucleotide analogues possessing different backbone topologies [41]. Ghadiri et al. employed this approach for an enzyme-free synthesis of an oligonucleotide

• analogue with a peptide backbone carrying nucleobases on its amino acid side chains [42] while Bradley et al. used the backbone of a peptide nucleic acid (PNA) with abasic sites which gives a reactive secondary amine for reversible attachment of aldehyde modified nucleobases [43]. Moreover, the DNA

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• the alkyne employed. Herein, we report the results of the synthesis and in vitro biological evaluation on the purified human recombinant cN-II of a series of beta-hydroxyphosphonate ribonucleosides including as nucleobases 4-substituted-1,2,3-triazoles (Figure 1). Results and Discussion Chemistry The

Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic–ribosome complex supervised by experiment and electronic structure methods

• Jörg Grunenberg and
• Giuseppe Licari

Beilstein J. Org. Chem. 2016, 12, 415–428, doi:10.3762/bjoc.12.45

• involved in the molecular recognition process. Our simulation could reproduce this high flexibility of the morpholine moiety, too (see Figure 6). Turning to the conformational changes in the receptor, they seem to be localized at the nucleobases G2540 and U2620 as well at the CCA-N-Phe unit. The

• force constant of 0.12 N/cm. This observation confirms the ester-type oxygen in the oxazolidinone ring as a hydrogen-bond acceptor. 4) Most important, the hydrogen bond between the G2540 nucleobase and the morpholine ring of linezolid is completely absent in the host/R-lzd complex. The nucleobases are

• modifications were introduced in candidates 17 and 18. Those candidates might lead to a better stacking interaction between the fluorophenyl moiety and the heteroaromatic crevice (A-site cleft). In addition, a larger aromatic system could lead to a closer contact between the B ring and the nucleobases A2486 and

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

• complexing more structurally challenging organic guests such as nucleobases. We quickly discovered that in chloroform solution, 4 and its analogs could bind nitrated aromatic compounds, such as 2,4,7-trinitrofluorenone. Nitrated polycyclic aromatics and polynitrated fluorenones were known pollutants so Kurt

Pd(OAc)₂-catalyzed dehydrogenative C–H activation: An expedient synthesis of uracil-annulated β-carbolinones

• Biplab Mondal,
• Somjit Hazra,
• Tarun K. Panda and
• Brindaban Roy

Beilstein J. Org. Chem. 2015, 11, 1360–1366, doi:10.3762/bjoc.11.146

• control agents for receptor research on bioenzyme inhibitors, such as the inhibition of HLE (human leukocyte elastase) [15][16][17][18]. Uracil, on the other hand, is one of the four nucleobases of RNA. It holds immense importance from a pharmaceutical and biological point of view [19]. For example, 5

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

• ; peptidic epitope; saccharide; Introduction This article describes the synthesis and evaluation of a new class of molecular conjugates that consist of a nucleobase, a peptidic epitope, and a saccharide. Nucleobases, amino acids, and saccharides are part of the unified building blocks of life [1] because

C-5’-Triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides: Synthesis and biological evaluation

• Roberto Romeo,
• Caterina Carnovale,
• Salvatore V. Giofrè,
• Maria A. Chiacchio,
• Adriana Garozzo,
• Emanuele Amata,
• Giovanni Romeo and
• Ugo Chiacchio

Beilstein J. Org. Chem. 2015, 11, 328–334, doi:10.3762/bjoc.11.38

• natural nucleobases with unnaturally-substituted heteroaromatics or homoaromatic systems, or the modification of the phosphate P(O)–O–C bond with the non–hydrolyzable phosphonate P(O)–C linkage [17][18]. In this context, nucleoside analogues, where different carbon or heterocyclic systems replace the

TEMPO-derived spin labels linked to the nucleobases adenine and cytosine for probing local structural perturbations in DNA by EPR spectroscopy

• Dnyaneshwar B. Gophane and
• Snorri Th. Sigurdsson

Beilstein J. Org. Chem. 2015, 11, 219–227, doi:10.3762/bjoc.11.24

• ][41][42], non-native base-pairing properties of nucleobases [43][44][45][46] and their dynamics [42][47][48]. Fluorescence spectroscopy, using environmentally sensitive fluorescent nucleosides has been used for detection of local structural perturbations [49][50][51][52][53][54][55][56][57], including