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

• efficient solid-phase-supported peptide synthesis (SPPS) of morpholinoglycine oligonucleotide (MorGly) mimics has been developed. The proposed strategy includes a novel specially designed labile linker group containing the oxalyl residue and the 2-aminomethylmorpholino nucleoside analogues as first subunits

• compounds 3a,d was published earlier [8]. Thymine containing morpholino nucleoside 3e was obtained similarly to 3d starting from the 5-methyluridine. See Supporting Information File 1 for the synthetic schemes, procedures and physicochemical data for intermediates in the synthesis of monomer 3e. Our next

• plates (Merck, Germany) in the proper solvent systems (see below) and visualized by UV irradiation, ninhydrin (amine groups) or cystein/aqueous sulfuric acid (nucleoside and trityl groups). Preparative silica gel column chromatography, RPC, and cation exchange chromatography were performed using silica

Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

• Oliver Ries,
• Martin Büschleb,
• Markus Granitzka,
• Dietmar Stalke and
• Christian Ducho

Beilstein J. Org. Chem. 2014, 10, 1135–1142, doi:10.3762/bjoc.10.113

• . Within the context of our work regarding the total synthesis of muraymycin nucleoside antibiotics, we have developed a synthetic approach towards (2S,3S)-3-hydroxyleucine building blocks. Application of different protecting group patterns led to building blocks suitable for C- or N-terminal

• ], as monosulfuric acid ester [6] or as potential acylation site for fatty acid side chains such as in A- and B-series muraymycin nucleoside antibiotics (Figure 1) [7][8][9]. In the case of these muraymycin congeners, acylation of the 3-hydroxy position with fatty acid side chains, which are ω

• , followed by concomitant acidic cleavage of the N,O- and O,O-acetal protecting groups leading to building block 22 in 89% yield (Scheme 3). Aldehyde 22 can be used for the connection of the (2S,3S)-3-hydroxyleucine motif of C-series muraymycins (such as muraymycin C1 (1c), Figure 1) to the nucleoside moiety

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• inexpensive phosphites (P(OR)3) have only been applied as phosphine substitutes in one single example: Beal [46] utilized tri-isopropylphosphite in a Mitsunobu condensation of a guanine-derived nucleoside analog with benzylic alcohols providing simplified byproduct separation through improved water solubility

Synthesis of nucleotide–amino acid conjugates designed for photo-CIDNP experiments by a phosphotriester approach

• Tatyana V. Abramova,
• Olga B. Morozova,
• Vladimir N. Silnikov and
• Alexandra V. Yurkovskaya

Beilstein J. Org. Chem. 2013, 9, 2898–2909, doi:10.3762/bjoc.9.326

• model compound conjugates of the amino acid, nucleotide, and dye residues, where key participants (dye, amino acid, and nucleoside) have to be drawn together mimicking the biologically important DNA repair processes. To fulfill the requirements of the photo-induced TR CIDNP experiments, a synthetic

• detection of elusive radicals in biomolecules using model compounds, where key participants of the reaction (dye, amino acid, and nucleoside) are spatially drawn together mimicking the biologically important DNA repair processes. Guanosine is the most easily oxidized nucleoside [12] in photoreactions of

• photoinitiating agents for electron transfer from nucleotides and amino acids [15][16][17][18]. Based on the above mentioned reasons, we have chosen 4-benzoylbenzoic acid, 2’-deoxyguanosine, and L-tryptophan [7][9][13][14][15][16][17][18][19][20] as the dye, nucleoside, and amino acid building blocks

Investigating the continuous synthesis of a nicotinonitrile precursor to nevirapine

• Ashley R. Longstreet,
• Suzanne M. Opalka,
• Brian S. Campbell,
• B. Frank Gupton and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2013, 9, 2570–2578, doi:10.3762/bjoc.9.292

• ; nicotinonitriles; Introduction Nevirapine (3) was the first commercially available non-nucleoside reverse transcriptase inhibitor (NNRTI), and has remained an important medicine in the management of human immunodeficiency virus (HIV) [1][2]. Nevirapine combined with lamivudine (3TC) and azidothymidine (AZT) or

Biosynthesis of rare hexoses using microorganisms and related enzymes

• Zijie Li,
• Yahui Gao,
• Hideki Nakanishi,
• Xiaodong Gao and
• Li Cai

Beilstein J. Org. Chem. 2013, 9, 2434–2445, doi:10.3762/bjoc.9.281

• pharmaceutical and nutrition industry [4]. In recent years, the interest in rare carbohydrates and the nucleosides (e.g. L-nucleoside analogues) derived from them has substantially increased in medicine because these molecules are potential candidates of anticancer and antiviral drugs [4][5][6]. Unfortunately

• oxygen. L-Talose and D-gulose The aldohexoses L-talose and D-gulose (C-3 epimer of D-galactose) are both very expensive owing to their scarcity in nature. L-Talofuranosyladenine, an adenine nucleoside derivative of L-talose, was found to be a slow-reacting substrate for calf intestinal adenosine

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

Diastereoselective synthesis of nitroso acetals from (S,E)-γ-aminated nitroalkenes via multicomponent [4 + 2]/[3 + 2] cycloadditions promoted by LiCl or LiClO₄

• Leandro Lara de Carvalho,
• Robert Alan Burrow and
• Vera Lúcia Patrocinio Pereira

Beilstein J. Org. Chem. 2013, 9, 838–845, doi:10.3762/bjoc.9.96

• diastereoselectively [1][2][3]. In contrast, the use of a chiral pool strategy, wherein the nitroalkene is the chiral source, is still scarce. To the best of our knowledge, only Chattopadhyaya et al. [18] and Cintas et al. [9] utilized chiral nitroalkenes, synthesized from a nucleoside and a carbohydrate, respectively

Facile synthesis of benzothiadiazine 1,1-dioxides, a precursor of RSV inhibitors, by tandem amidation/intramolecular aza-Wittig reaction

• Krishna C. Majumdar and
• Sintu Ganai

Beilstein J. Org. Chem. 2013, 9, 503–509, doi:10.3762/bjoc.9.54

• activity [16][17][18][19][20][21][22], including hypoglycemic (1), anti-HIV (2), HIV-1 specific non-nucleoside reverse transcriptase inhibitor (3), sedative (4), and respiratory syncytial virus (RSV) inhibitory activity (5; Figure 1). A literature search revealed that the 1,2,4-benzothiadiazine 1,1

A new synthetic access to 2-N-(glycosyl)thiosemicarbazides from 3-N-(glycosyl)oxadiazolinethiones and the regioselectivity of the glycosylation of their oxadiazolinethione precursors

• El Sayed H. El Ashry,
• El Sayed H. El Tamany,
• Mohy El Din Abdel Fattah,
• Mohamed R. E. Aly,
• Ahmed T. A. Boraei and
• Axel Duerkop

Beilstein J. Org. Chem. 2013, 9, 135–146, doi:10.3762/bjoc.9.16

• with inhibition constants in the low micromolar range [2]. Coupling of aglycones with relevant glycosyl donors is the common approach involved in the synthesis of most nucleosides. Another strategy for the synthesis of nucleoside analogues is the use of glycosylamines and related N-bonded glycosides [3

An improved synthesis of a fluorophosphonate–polyethylene glycol–biotin probe and its use against competitive substrates

• Hao Xu,
• Hairat Sabit,
• Gordon L. Amidon and
• H. D. Hollis Showalter

Beilstein J. Org. Chem. 2013, 9, 89–96, doi:10.3762/bjoc.9.12

• the labelling efficiency of the FP–PEG–biotin probe 1 synthesized by our new route, we utilized it in the purification of four arbitrarily mixed proteins including bovine serum albumin (BSA), porcine carboxylesterase (pCES), nucleoside phosphorylase (NP), and trypsin (Figure 2A). Thus, the protein

Studies on the substrate specificity of a GDP-mannose pyrophosphorylase from Salmonella enterica

• Lu Zou,
• Ruixiang Blake Zheng and
• Todd L. Lowary

Beilstein J. Org. Chem. 2012, 8, 1219–1226, doi:10.3762/bjoc.8.136

• sugar nucleotides is therefore a topic of continuing interest [6]. The classical method for chemically synthesizing sugar nucleotides involves the preparation of a sugar 1-phosphate derivative followed by its coupling to an activated nucleoside monophosphate to form the key pyrophosphate moiety (Figure

Diarylethene-modified nucleotides for switching optical properties in DNA

• Sebastian Barrois and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2012, 8, 905–914, doi:10.3762/bjoc.8.103

• switching of optical properties in DNA can be achieved selectively at 310 nm (forward) and 450 nm (backward); both wavelengths are outside the normal nucleic acid absorption range. Moreover, this nucleoside was proven to be photochemically stable and allows switching back and forth several times. These

• . Diarylethenes have been applied in a noncovalent chiroptical photoswitchable DNA complex [33] and combined with 7-deazaadenosine to obtain a nucleosidic diarylethene switch [34]. Recently, we reported, very preliminarily, the preparation and optical properties of nucleoside 4 [30]. Herein, we give a full

• account and present the detailed synthesis of diarylethene-modified nucleosides 4, 5 and 6 (Scheme 1), and the characterization of their photochromic behavior. It turned out to be most promising to continue the DNA work with the modified and photochromic nucleoside 4, which was, thus, incorporated into

Enantioselective supramolecular devices in the gas phase. Resorcin[4]arene as a model system

• Caterina Fraschetti,
• Matthias C. Letzel,
• Antonello Filippi,
• Maurizio Speranza and
• Jochen Mattay

Beilstein J. Org. Chem. 2012, 8, 539–550, doi:10.3762/bjoc.8.62

• [VR∙H∙dC]+ complex does not uptake B, whereas its diastereoisomers are able to efficiently capture B and to proceed to the nucleoside displacement. This very sensitive system strongly resembles the electronic concept of a logic gate. Indeed, depending on the relative configuration of the

• supramolecular device and of the neutral gas B, the transported nucleoside can or cannot be released. This effect is outstanding for the [VR/S∙H∙dC]+ aggregates, which, if “stimulated” by a reactant characterized by the correct configuration, can selectively release one enantiomer of a chiral guest and keep the

Azobenzene dye-coupled quadruply hydrogen-bonding modules as colorimetric indicators for supramolecular interactions

• Yagang Zhang and
• Steven C. Zimmerman

Beilstein J. Org. Chem. 2012, 8, 486–495, doi:10.3762/bjoc.8.55

• ]. Indeed, several syntheses of the DAN unit are now available [29][30][31][32][33][34]. The original UG unit contains a labile nucleoside unit, but a DeUG unit [35] and more recently a DeUG module bearing a range of synthetic handles for further elaboration [36] were both reported with more scalable

Selectivity in C-alkylation of dianions of protected 6-methyluridine

• Ngoc Hoa Nguyen,
• Christophe Len,
• Anne-Sophie Castanet and
• Jacques Mortier

Beilstein J. Org. Chem. 2011, 7, 1228–1233, doi:10.3762/bjoc.7.143

• parameters that are critical for the design of new nucleoside drug candidates [4][5][6][7][8]. These cyclic compounds are expected to have a beneficial biological impact especially toward enzymatic repair processes [9]. As part of an ongoing program directed by one of us (C. L.) toward the synthesis and

• construction of C-substituted nucleosides are based on ring lithiation of nucleoside derivatives followed by their reaction with appropriate electrophiles. Thus, sequential lithiation of 2',3'-O-isopropylideneuridine (6) with LDA in THF (Figure 1) and electrophilic quenching with n-bromobutane was reported to

• organolithiums [14], and indeed, 7 failed to react, in our experiments, with 4-bromo-but-1-ene to give 9. We then turned our attention to the metalation of the 5'-O-TBDMS protected nucleoside 10 (Figure 2). Treatment with LDA (5 equiv) in THF at −70 °C followed by addition of D2O provided 12 in 82% yield

Synthesis, reactivity and biological activity of 5-alkoxymethyluracil analogues

• Lucie Brulikova and
• Jan Hlavac

Beilstein J. Org. Chem. 2011, 7, 678–698, doi:10.3762/bjoc.7.80

• , cytotoxic and antibacterial, is also reported. Keywords: 5-alkoxymethyluracil; biological activity; nucleosides; Review Introduction Modifications of nucleic acid components play a significant role in the field of nucleic acids research. In particular, nucleoside analogues find broad therapeutic

• nucleoside 1, Bergstrom and co-workers reported a presumed mechanism for its formation (Scheme 1) [8]. In addition, they also focused their research on isopropyloxy analogue 2. Reaction of 3,3,3-trifluoropropene with 5-chloromercuri-2'-deoxyuridine (4) in methanol gave two major products (E)-5-(3,3,3

• localization agents, Iwashina and co-workers investigated the radiolabelled 5-(1-methoxy-2-iodoethyl) nucleoside 31 (Figure 4) [15] which was obtained by radio-iodination of 5-(1-methoxy-2-iodoethyl)-2'-deoxyuridine (28) via isotope exchange by the pivalic acid melt method. In addition to the above mentioned 5

Oxalyl retro-peptide gelators. Synthesis, gelation properties and stereochemical effects

• Janja Makarević,
• Milan Jokić,
• Leo Frkanec,
• Vesna Čaplar,
• Nataša Šijaković Vujičić and
• Mladen Žinić

Beilstein J. Org. Chem. 2010, 6, 945–959, doi:10.3762/bjoc.6.106

• Janja Makarevic Milan Jokic Leo Frkanec Vesna Caplar Natasa Sijakovic Vujicic Mladen Zinic Laboratory for Supramolecular and Nucleoside Chemistry, Ruđer Bošković Institute, P.O.B. 180, HR-10002 Zagreb, Croatia 10.3762/bjoc.6.106 Abstract In this work we report on gelation properties, self

Synthesis of 5-(6-hydroxy-7H-purine-8-ylthio)- 2-(N-hydroxyformamido)pentanoic acid

• Yanmei Zhang,
• Greg Elliot,
• Adrian Saldanha,
• Igor Tsigelny,
• Dennis Carson and
• Wolf Wrasidlo

Beilstein J. Org. Chem. 2010, 6, 742–747, doi:10.3762/bjoc.6.93

• a nucleoside. A prototype compound was designed and docked into the catalytic domain of the AdSS enzyme bridging the region between the magnesium center of the protein to the nucleoside region. The synthesis involves coupling a brominated peptide fragment capable of complexing magnesium to a

• thiolated nucleoside to obtain the hybrid model compound. Keywords: adenylosuccinate synthetase (AdSS); thiolated nucleoside; Introduction During cell proliferation, adenine nucleotides for nucleic acid synthesis are generated through a de novo biosynthetic route, which requires the key enzyme

Kinetic studies and predictions on the hydrolysis and aminolysis of esters of 2-S-phosphorylacetates

• Milena Trmčić and
• David R. W. Hodgson

Beilstein J. Org. Chem. 2010, 6, 732–741, doi:10.3762/bjoc.6.87

• use of bromoacetate-based cross-linking agents with thiophosphate nucleophiles 3, where our aim was to generate nucleoside-pyrophosphate mimics as potential glycosyl transferase inhibitors under aqueous conditions. Initially, we focus on the use of the bromoacetic acid esters of N-hydroxybenzotriazole

A novel and efficient method to prepare 2-aryltetrahydrofuran-2-ylphosphonic acids

• Vsevolod V. Komissarov,
• Anatoly M. Kritzyn and
• Jouko J. Vepsäläinen

Beilstein J. Org. Chem. 2010, 6, No. 63, doi:10.3762/bjoc.6.63

• [1][2][3][4]. As a part of our ongoing project, it seemed important to synthesize compounds with phosphonate and phenyl groups at one end of the hydrocarbon chain and a nucleic base residue at the other end. Previously, it was shown that compounds with similar structures inhibit purine nucleoside

Synthesis of some novel hydrazono acyclic nucleoside analogues

• Mohammad N. Soltani Rad,
• Ali Khalafi-Nezhad and
• Somayeh Behrouz

Beilstein J. Org. Chem. 2010, 6, No. 49, doi:10.3762/bjoc.6.49

• using phenylhydrazine. To interpret the dominant formation of (E)-hydrazone derivatives rather than (Z)-isomers, PM3 semiempirical quantum mechanic calculations were carried out which indicated that the (E)-isomers had the lower heats of formation. Keywords: acyclic nucleoside; chemotherapeutic agent

• antineoplastic (e.g. bisantrene [4][10]), contain a hydrazone moiety in their structure. Furthermore, various structurally related miconazole bioactive hydrazones are known as antimicrobial and antifungal agents [11][12]. The significance of nucleoside chemistry in drug discovery is well-known and fully

• established in medicinal chemistry [13][14][15][16]. Acyclic nucleosides constitute a special class of nucleoside analogues which have attracted great interest due to their broad-spectrum chemotherapeutic activities against cancer and infections caused by viruses, microbes and other pathogenic microorganisms

The C–F bond as a conformational tool in organic and biological chemistry

• Luke Hunter

Beilstein J. Org. Chem. 2010, 6, No. 38, doi:10.3762/bjoc.6.38

• amount of research into fluorinated nucleoside analogues as potential treatments for cancer and viral infection [21][22]. Fluorine is an obvious choice for incorporating into sugar-modified nucleoside analogues, since fluorine can be considered a reasonable mimic of either a hydrogen atom or a hydroxyl

Symmetrical and unsymmetrical α,ω-nucleobase amide-conjugated systems

• Sławomir Boncel,
• Maciej Mączka,
• Krzysztof K. K. Koziol,
• Radosław Motyka and
• Krzysztof Z. Walczak

Beilstein J. Org. Chem. 2010, 6, No. 34, doi:10.3762/bjoc.6.34

• ]. Moreover, α,ω-nucleobase amide-conjugated molecules possess the tendency to form meta-stable complexes with DNA and thus can perturb the cell replication. For example, amide-linked heterodimer synthons consisting of acyclic nucleoside units and 5′-amino-2′,5′-dideoxythymidine are PNA/DNA chimeras (V) [4

• of 1ea shown as thermal ellipsoids at 50% probability [17][18]. DMT-MM in its presumably more stable conformation [20]. TEM images of symmetrical α,ω-nucleobase amide-conjugated systems: A – two splitting nucleoside nanofibres growing out from crystalline phase (11), the rectangular area (A) shows

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

• José L. Jiménez Blanco,
• Fernando Ortega-Caballero,
• Carmen Ortiz Mellet and
• José M. García Fernández

Beilstein J. Org. Chem. 2010, 6, No. 20, doi:10.3762/bjoc.6.20

• derivatives with tendency to adopt specific compact conformations (foldamers). Linear naturally-occurring SAA homo-oligomers SAAs occur extensively in nature as subunits of oligosaccharides in cell walls such as N-acetylneuraminic 1 and muramic acids 2, as well as in some nucleoside antibiotics (e.g

• positively charged isothiouronium inter-nucleoside linkages into otherwise negatively charged DNA (Figure 17) [83][84]. The binding of these artificial DNAs (DNmt or DNT) to its complementary DNA strand occurs as with the unmodified DNA·DNA duplex but with enhanced nuclease resistance. In order to design