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

NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A–T phosphoramidite building blocks

• Boris Schmidtgall,
• Claudia Höbartner and
• Christian Ducho

Beilstein J. Org. Chem. 2015, 11, 50–60, doi:10.3762/bjoc.11.8

• phosphoramidites with X representing pyrimidine or purine nucleobases appears to be feasible. This will enable the preparation of NAA-modified oligonucleotides with significant variations in the base sequence. We are currently finishing the synthesis of a comprehensive set of corresponding X–T phosphoramidites

• with fully zwitterionic backbone structures and also on the interaction of NAA-modified oligonucleotides with proteins such as nucleases and polymerases. Design concept of nucleosyl amino acid (NAA)-modified oligonucleotides 5 formally derived from structures 1–4 (B1, B2 = nucleobases); previously

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• such as the nucleobases: protected cytosine, guanine 87, adenine, and thymine to afford azanucleoside products such as 88 (Scheme 20). The use of the Shono-type electrooxidation in peptide and peptidomimetic chemistry The preparation of a bridged tricyclic analogue to induce an α-helix conformation in

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• cases a switch of the binding site to the minor groove was reported. In an effort to influence DNA sequence-selective recognition by small molecules (MW <1000), our group prepared a series of phenanthridine derivatives with one or two nucleobases covalently attached at the 3 and/or 8 positions of the

• nucleobases (5'-dGMP) in respect to less efficient binding of sulfur-containing nucleophiles present in resistance processes within the cell. Phenanthridine covalently bound to DNA and RNA The phenanthridine aromatic moiety curvature nicely fits the shape of an average DNA and RNA basepair, while the length

• magnitude lower affinity toward poly(A) in comparison to PHEN-Me and PHEN-H+, which could be attributed to the steric hindrance of EB at C6 and N5 positions to the optimal orientation of phenanthridinium within the intercalative binding site between adjacent nucleobases. As expected, bis-phenanthridine

Synthesis of novel conjugates of a saccharide, amino acids, nucleobase and the evaluation of their cell compatibility

• Dan Yuan,
• Xuewen Du,
• Junfeng Shi,
• Ning Zhou,
• Abdulgader Ahmed Baoum and
• Bing Xu

Beilstein J. Org. Chem. 2014, 10, 2406–2413, doi:10.3762/bjoc.10.250

• evolution, nature selects saccharides, peptides, and nucleobases as the fundamental building blocks for the creation of biomacromolecules, which lay the molecular foundations of life. This simple fact and the self-assembly of small molecules in water have inspired us to explore the conjugates of those three

Autonomous assembly of synthetic oligonucleotides built from an expanded DNA alphabet. Total synthesis of a gene encoding kanamycin resistance

• Kristen K. Merritt,
• Kevin M. Bradley,
• Daniel Hutter,
• Mariko F. Matsuura,
• Diane J. Rowold and
• Steven A. Benner

Beilstein J. Org. Chem. 2014, 10, 2348–2360, doi:10.3762/bjoc.10.245

• fragments of synthetic single-stranded DNA. This strategy uses an artificially expanded genetic information system (AEGIS) that adds nucleotides to the four (G, A, C, and T) found in standard DNA by shuffling hydrogen-bonding units on the nucleobases, all while retaining the overall Watson–Crick base

• reliably self-assemble upon simple mixing. Even with explicit design, the number of fragments that can be self-assembled appears to be not much larger. This is because of properties intrinsic in the structure of the nucleobases themselves. First, even if rule-based Watson–Crick pairing were the only

• -bonding units displayed by the nucleobases, allowing them to pair orthogonally within the geometry of the Watson–Crick pair (Figure 2). With higher information density in AEGIS, more fragments should self-assemble with fewer off-target hybridization, fewer hairpins, and fewer close mismatches that slow

Specific DNA duplex formation at an artificial lipid bilayer: fluorescence microscopy after Sybr Green I staining

• Emma Werz and
• Helmut Rosemeyer

Beilstein J. Org. Chem. 2014, 10, 2307–2321, doi:10.3762/bjoc.10.240

• containing 6 nucleobases. Experimental setup. Schematic drawing of the laser scanning microscope, the optical transparent microfluidic bilayer slide, and the lipid bilayer with the incorporated double-tailed lipo-oligonucleotides as well as of Sybr Green I, forming a membrane - bound nucleic acid duplex–dye

Reversibly locked thionucleobase pairs in DNA to study base flipping enzymes

• Christine Beuck and
• Elmar Weinhold

Beilstein J. Org. Chem. 2014, 10, 2293–2306, doi:10.3762/bjoc.10.239

• opposing adenine, resulting in ring opening and formation of an ethylene cross-linked base pair [29][30]. Other aziridine-substituted nucleobases have been incorporated enzymatically by a DNA polymerase, but elongation past the modified nucleoside has not been reported [31]. Another approach uses

• nucleobases in which an exocyclic functionality has been substituted by a vinyl group. Upon hybridization with a complimentary, unmodified strand, the vinyl group is attacked by the nucleophilic exo- or endocyclic nitrogen of the partnering base, forming a cross-linked base pair [32][33][34]. While the cross

• using a commercially available cyanoethyl protected phosphoamidite for dG6S and dU4S or by postsynthetic modification of convertible nucleoside precursors for dI6S and dU4S [51]. The ideal geometry of a Watson–Crick base pair within B-DNA is a coplanar orientation of the two nucleobases, stacked between

Molecular recognition of AT-DNA sequences by the induced CD pattern of dibenzotetraaza[14]annulene (DBTAA)–adenine derivatives

• Marijana Radić Stojković,
• Marko Škugor,
• Łukasz Dudek,
• Jarosław Grolik,
• Julita Eilmes and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2175–2185, doi:10.3762/bjoc.10.225

• determined as the concentration of nucleobases. Spectrophotometric titrations were performed at pH 7.0 (I = 0.05 mol dm−3, buffer sodium cacodylate) by adding portions of polynucleotide solution into the solution of the studied compound for UV–vis. CD experiments were carried out by adding portions of

Synthesis and optical properties of pyrrolidinyl peptide nucleic acid carrying a clicked Nile red label

• Nattawut Yotapan,
• Chayan Charoenpakdee,
• Pawinee Wathanathavorn,
• Boonsong Ditmangklo,
• Hans-Achim Wagenknecht and
• Tirayut Vilaivan

Beilstein J. Org. Chem. 2014, 10, 2166–2174, doi:10.3762/bjoc.10.224

• Nile red label by neighboring G than by other nucleobases. A is almost non-quenching as shown by the high quantum yield of 11merAA-Nr (ΦF = 0.15), which is comparable to the high quantum yield of the free Nile red label (ΦF = 0.14). On the other hand, the presence of two flanking G in 11merGG-Nr

Second generation silver(I)-mediated imidazole base pairs

• Susanne Hensel,
• Nicole Megger,
• Kristina Schweizer and
• Jens Müller

Beilstein J. Org. Chem. 2014, 10, 2139–2144, doi:10.3762/bjoc.10.221

• functional moieties have been introduced into various nucleic acid building blocks, including, for example, modified nucleobases and modified sugar entities. A recent addition is the application of ligand systems as nucleobases surrogates [5][6][7][8][9]. In the presence of suitable transition metal ions, so

• -called metal-mediated base pairs between two complementary ligand-derived artificial nucleobases can be formed. Accordingly, metal-based functionality can be introduced site-specifically into nucleic acids. Various applications have been reported for such metal-modified nucleic acids [5], including

• necessarily require the presence of artificial ligands. In contrast, natural nucleobases have also been successfully applied in the generation of metal-mediated base pairs such as thyminate–Hg(II)–thyminate or cytosine–Ag(I)–cytosine [23][24][25]. It has even been shown that polymerases are capable of

Synthesis of phosphoramidites of isoGNA, an isomer of glycerol nucleic acid

• Keunsoo Kim,
• Venkateshwarlu Punna,
• Phaneendrasai Karri and
• Ramanarayanan Krishnamurthy

Beilstein J. Org. Chem. 2014, 10, 2131–2138, doi:10.3762/bjoc.10.220

• that the base-pairing properties were unpredictably different from other closely related acyclic nucleic acids [8]. This indicated that the nature of the backbone exerts a strong influence on the disposition of the nucleobases, and there seems to be no straightforward correlation between the nature of

• for the introduction of the canonical nucleobases by a SN2 displacement reaction. At this point, we chose the Mitsunobu reaction (Scheme 1), which has been widely employed [16]. The reaction with the N3-benzoyl protected thymine delivered 5 in good yield. However, the reaction with N6-benzoyladenine

• protecting group approach. We silylated 1 to afford 8 whose ketal was deprotected followed by tritylation to give the derivative 10, which is expected to be suited for the introduction of nucleobases by an SN2 reaction (Scheme 2). Once again, the Mitsunobu reaction with thymine proceeded smoothly. However

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

• , nucleosides and nucleobases play an important role in all biological systems. Therefore, it is not surprising that many of their analogs possess interesting biological properties. Potent antiviral drugs based on phosphonate nucleotides 1a–c [1][2], 2a–d and 3a–d (Figure 1) have been reported. Prodrugs of

• 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

• the compounds exist as zwitterions with a hydrogen bond between the negatively charged phosphonate moiety and the positively charged pyrrolidine nitrogen atom in the range of pD 3–9. The pD titration experiments have also revealed the deuteration/dedeuteration of adenine and thymine nucleobases. In

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

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

• RNA catalysts that support an aldol reaction between an aldehyde and a ketone, relevant to the synthesis of sugars [6], or the linkage of ribose to nucleobases to generate nucleotides [7]. Such ribozymes are seen as important functional entities underscoring the RNA world theory, where ribonucleic

OligArch: A software tool to allow artificially expanded genetic information systems (AEGIS) to guide the autonomous self-assembly of long DNA constructs from multiple DNA single strands

• Kevin M. Bradley and
• Steven A. Benner

Beilstein J. Org. Chem. 2014, 10, 1826–1833, doi:10.3762/bjoc.10.192

• genetic information system (AEGIS) [3][9]. AEGIS adds nucleotide building blocks to the four found in standard DNA (G, A, C, and T) by shuffling hydrogen-bonding units on the nucleobases, all while retaining the overall Watson–Crick nucleobase pairing geometry (Figure 2). These extra nucleotides bind to

• ” self-assembly by greatly increasing the number of possible unique fragments and maximize uniqueness of fragment ends. Of course, a large DNA construct built with AEGIS nucleobases would, after it is assembled, still contain AEGIS components. For those who want an entirely natural end product, this is

• array. In designating potential substitutions, each of three categories of sequence regions have distinct rules: Protein-coding regions: AEGIS nucleobases can be substituted only at the third site in codons where any nucleobase in the third position produces the same amino acid (Leu, Val, Ser, Pro, Thr

Concise total synthesis of two marine natural nucleosides: trachycladines A and B

• Haixin Ding,
• Wei Li,
• Zhizhong Ruan,
• Ruchun Yang,
• Zhijie Mao,
• Qiang Xiao and
• Jun Wu

Beilstein J. Org. Chem. 2014, 10, 1681–1685, doi:10.3762/bjoc.10.176

• ), nucleoside 3 could be synthesized by using 1,2,3,5-tetra-O-benzoyl-2-C-methyl-D-ribofuranose (5) as a carbohydrate acceptor by a Vorbrüggen glycosylation with the corresponding silylated nucleobases and a Lewis acid as a catalyst. As the key intermediate for the preparation of the anti-HCV nucleoside

Influence of perylenediimide–pyrene supramolecular interactions on the stability of DNA-based hybrids: Importance of electrostatic complementarity

• Christian B. Winiger,
• Simon M. Langenegger,
• Oleg Khorev and
• Robert Häner

Beilstein J. Org. Chem. 2014, 10, 1589–1595, doi:10.3762/bjoc.10.164

• sciences. They play a crucial role in the stacking of nucleobases, thus stabilising the DNA double helix. The following paper describes a series of chimeric DNA–polycyclic aromatic hydrocarbon (PAH) hybrids. The PAH building blocks are electron-rich pyrene and electron-poor perylenediimide (PDI), and were

• linked by negatively charged phosphodiester groups [29]. The importance of aromatic and hydrophobic factors for duplex stability was demonstrated by replacing the natural nucleobases by size expanded analogs [30][31][32][33][34][35]. A classic example of polymeric donor–acceptor complexes are the

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

• synthetic oligonucleotides (Thermo-Fisher Scientific, HPLC-grade) were prepared in double-distilled water, and the PNA concentration was calculated by UV absorbance with the following extinction coefficients (ε260 [M–1cm–1]) for the nucleobases: T 8600, T* 14938 (pyrene-modified monomer, see Supporting

• into the major groove; (b) pyrene-modified uracil derivative used in PNA monomer in the present study; (c) sequences of PNA and DNA used. T indicates pyrene modified nucleobases; bold letters indicate the position of W1282X point mutation. Fluorescence spectra at 347 nm excitation, recorded at 20 °C of

Solid-phase-supported synthesis of morpholinoglycine oligonucleotide mimics

• Tatyana V. Abramova,
• Sergey S. Belov,
• Yulia V. Tarasenko and
• Vladimir N. Silnikov

Beilstein J. Org. Chem. 2014, 10, 1151–1158, doi:10.3762/bjoc.10.115

• of the uracil nucleobases in the MorGly oligomers by thymines with better stacking properties may solve this problem. The synthesis of the thymine containing morpholino monomer 1e was necessary to prove this hypothesis. The promising properties of the MorGly oligomers as potential antisense agents

• nucleobases can be performed simultaneously by treatment with aqueous ammonia as in the solid phase synthesis of native oligonucleotides (ODN) [21]. The oxalyl-mediated attachment of the growing chain to the solid support is usual in the synthesis of base sensitive ODN derivatives [22]. Figure 3 indicates the

• -containing residue to the morpholine nitrogen in monomers 5a,d,e resulted in the appearance of duplicate signals of the nucleobases and morpholine protons in the NMR spectra (see Experimental) similar to morpholinooxalyl nucleosides [8]. After completion of the loading, the unreacted amino groups were capped

Self-assembly of 2,3-dihydroxycholestane steroids into supramolecular organogels as a soft template for the in-situ generation of silicate nanomaterials

• Valeria C. Edelsztein,
• Andrea S. Mac Cormack,
• Matías Ciarlantini and
• Pablo H. Di Chenna

Beilstein J. Org. Chem. 2013, 9, 1826–1836, doi:10.3762/bjoc.9.213

• stimuli such as light, ultrasound or chemical stimuli [8][9][10][11][12]. A wide variety of structurally diverse molecules have the ability to form physical gels (e.g., saccharides, peptides, ureas, nucleobases, steroids, dendrimers, etc. [13]). Although a great effort has been made to investigate the

Enhancement of efficiency in organic photovoltaic devices containing self-complementary hydrogen-bonding domains

• Rohan J. Kumar,
• Jegadesan Subbiah and
• Andrew B. Holmes

Beilstein J. Org. Chem. 2013, 9, 1102–1110, doi:10.3762/bjoc.9.122

• systems and dimerized nucleobases; however, in these cases an upfield change in chemical shift is generally observed, [5][30] in contrast to the downfield movement in chemical shift observed for the vinyl proton in compound 2. Non-specific van der Waals interactions are typically weaker than hydrogen

Synthesis of trifunctional cyclo-β-tripeptide templates

• Frank Stein,
• Tahir Mehmood,
• Tilman Plass,
• Javid H. Zaidi and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2012, 8, 1576–1583, doi:10.3762/bjoc.8.180

• such as nucleobases on the template provides a specific hydrogen-bonding network orthogonal to the peptide ring aggregation, which will be of value for aggregate formation and molecular architectures defined by a three-dimensional network of hydrogen bonds. Selective release of the first amino group

• -penetrating peptide, which can be further functionalized with any biologically active molecule bearing an alkyne. Potentially, this generates a fluorescent and cell-permeable drug applicable for in vivo experiments and other biochemical assays. In addition, different nucleobases were linked to the central

Carbasugar analogues of galactofuranosides: α-O-linked derivatives

• Jens Frigell and
• Ian Cumpstey

Beilstein J. Org. Chem. 2010, 6, 1127–1131, doi:10.3762/bjoc.6.129

• carbocyclic ring as the β-talo epoxide 4, were opened by nitrogen nucleophiles (nucleobases [18] or azide [19][20]) with generally good regioselectivity for attack at C1. The only precedent for attack at such carbapentafuranose epoxides with an oxygen nucleophile would appear to be the acid-mediated attack of