Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• are among the best methods to prepare C-arylglycosides, C-nucleosides and C-glycosidic oligomers when new artificial pharmacophores are approached [17]. With Suzuki cross-couplings C-glycoside analogues of phloriain with antidiabetic properties [18] or aryl-scaffolded dimers and trimers were

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• nucleosides resulted in the development of a group of compounds referred to as nucleoside analogs (Figure 1). The essential role of nucleoside analogs in medicine is reflected by the fact that currently thirty-six compounds from this class are used throughout the world in the therapy of viral or cancer

• educts contribute the majority of the novel skeleton of the product” [44]. In this review, we understand educts as compounds that contribute carbon atoms to the MCR product [45]. By the analogy to nucleosides included in the DNA/RNA nucleic acids, this review is limited to MCRs involving furanosyl

• nucleosides as (i) reaction components, or (ii) products obtained from non-nucleoside substrates. The cited references are grouped according to the usually recognized types of the MCRs [46]. Review 1. The Mannich reaction The classical Mannich reaction yields β-aminoaldehydes or β-aminoketones and involves

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

• perbenzylated 1-O-methyl-5-deoxyribofuranose. The enzyme adenylate deaminase (EC 3.5.4.6) was successfully applied to the chemoenzymatic synthesis of trachycladines B. Keywords: marine nucleosides; natural products; total synthesis; trachycladines A and B; Vorbrüggen glycosylation; Introduction Marine

• organisms are a main source for the great diversity of naturally occurring nucleosides [1], which play an important role in medical research and pharmaceutical development, especially for the clinical treatment against malignant proliferation and infections by fungi, bacteria and viruses [2][3][4][5][6][7

• ]. The initial discovery of marine nucleosides can be traced back to the identifications of spongothymidine and spongouridine in the early 1950s from the Caribbean sponge Tethyacrypta [8][9], which subsqeuently led to the commercialization of arabinofuranosylcytosine (Ara-C) [10], arabinofuranosyladenine

The chemoenzymatic synthesis of clofarabine and related 2′-deoxyfluoroarabinosyl nucleosides: the electronic and stereochemical factors determining substrate recognition by E. coli nucleoside phosphorylases

• Ilja V. Fateev,
• Konstantin V. Antonov,
• Irina D. Konstantinova,
• Tatyana I. Muravyova,
• Frank Seela,
• Roman S. Esipov,
• Anatoly I. Miroshnikov and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2014, 10, 1657–1669, doi:10.3762/bjoc.10.173

• -chloroadenine nucleosides were studied and compared with the activities of 2-deoxy-2-fluoro-D-arabinose. As expected, D-ribose exhibited the best substrate activity [90% yield of 2-chloroadenosine (8) in 30 min], D-arabinose reached an equilibrium at a concentration of ca. 1:1 of a starting base and the formed

• nucleosides 9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-2-chloroadenine (1; clofarabine) has recently attracted a lot of attention owing to its successful application for the treatment of pediatric acute leukemia [5][6][7][8][9]. As might be expected, a great number of publications are devoted to the synthesis

• -di-O-(tri-isopropylsilyl)-α-D-arabinofuranosyl chloride, the condensation of which with 2,6-dichloropurine gave an 1:3.5 α/β mixture of the relevant nucleosides. This mixture was treated with ammonia to replace the C-6 chlorine with an amino group, separated into individual anomers, and the β-anomer

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• ; stereoselective amine synthesis; triol synthesis; Introduction 7-Deazapurine (pyrrolo[2,3-d]pyrimidine) nucleosides are commonly found in nature playing a variety of roles such as building blocks of nucleic acids and tRNA, metabolites or antimetabolites [1]. Deazapurine ribonucleosides also show interesting

• pharmacological profiles including antibacterial, antiviral and anticancer properties [2][3][4]. Nucleoside Q precursor (PreQ0) 1 is a common precursor in the biosynthesis of queuosine (Q, 2) and archaeosine (G+, 3), two hyper-modified nucleosides present in the tRNA of prokaryote/eukaryote and euryarchaeota

• the subject of extensive study [1] and several syntheses of the PreQ0 base or ribonucleoside [9][10][11][12][13][14][15][16] and queuosine [17] have been reported in the literature. Despite this long-lasting interest, examples of purine-based nucleosides containing a sugar or carbosugar motif at the 4

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

• labile linker between the solid support and the growing oligomer chain (Figure 3) during SPPS in combination with the tert-butyloxycarbonyl (Boc)- and acyl-protected morpholino nucleosides. After completion of the synthesis, the cleavage of the oligomer from the solid support and the deprotection of

• necessity of using monomers 2 (Scheme 1) as first subunits bound to the support through the oxalyl linker. We synthesized Boc-protected aminomethylmorpholino nucleosides 2a,d,e as shown in Scheme 1 starting from aminomethylmorpholino nucleosides 3a,d,e. The synthesis of adenine and uracil containing

• -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

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

• standards, the use of the hyperpolarization approach is extraordinary to elucidate the interactions between hidden transient intermediates of nucleosides and amino acids in conjugates, which mimic biologically relevant processes. The liquid phase synthesis (LPS) in combination with the phosphotriester

• solvent systems (see below) and spots were visualized by UV irradiation, ninhydrin (for amine groups) or cysteine/aqueous sulfuric acid (for nucleosides and tryptophan) solution. Evaporations were performed under reduced pressure at 40 °C. The preparative silica gel column chromatography was performed

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

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

Damage of polyesters by the atmospheric free radical oxidant NO₃^•: a product study involving model systems

• Catrin Goeschen and
• Uta Wille

Beilstein J. Org. Chem. 2013, 9, 1907–1916, doi:10.3762/bjoc.9.225

• the strongest free-radical oxidants known [E(NO3•/NO3−) = 2.3–2.5 V vs NHE] [9], and recent product studies by us revealed that NO3• readily damages aromatic amino acids and pyrimidine nucleosides through an oxidative pathway [10][11][12][13]. Thus, the ease by which model compounds of biologically

• ratio towards the nitrate 4 at expense of the higher oxidized products 5 and 6 (data not shown). The observed side-chain oxidation in 3 by NO3• is similar to the outcome of the reaction of thymidine nucleosides with NO3•, where oxidative transformation of the methyl substituent in the heterocyclic base

• for the reaction of NO3• with alkylaromatic compounds [22][23]. In the absence of any reactants the resulting radical cation 3•+ undergoes deprotonation to give benzyl radical 7, in analogy to the mechanism of the NO3•-induced oxidation of aromatic amino acids and nucleosides [10][11][12][13]. This

Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

• Sándor B. Ötvös,
• Ádám Georgiádes,
• István M. Mándity,
• Lóránd Kiss and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1508–1516, doi:10.3762/bjoc.9.172

• in Figure 1) [8][9]. The 1,2,3-triazole moiety is a constituent part of many modified nucleosides or carbanucleosides with antiviral, anti-HIV or cytostatic activities [10][11][12]. However, the scope of triazole chemistry is not confined to drug discovery. There are an increasing number of

Conformational analysis and intramolecular interactions in monosubstituted phenylboranes and phenylboronic acids

• Josué M. Silla,
• Rodrigo A. Cormanich,
• Roberto Rittner and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2013, 9, 1127–1134, doi:10.3762/bjoc.9.125

• transpeptidases [1][2]. Other important studies incorporate the boronic acid moiety into amino acids and nucleosides as antitumor and antiviral agents [3][4]. Indeed, the great importance of aromatic boronic acids to biological and pharmaceutical purposes has been reported, as well as the interest to introduce a

Methylidynetrisphosphonates: Promising C₁ building block for the design of phosphate mimetics

• Vadim D. Romanenko and
• Valery P. Kukhar

Beilstein J. Org. Chem. 2013, 9, 991–1001, doi:10.3762/bjoc.9.114

• and coordination properties thus providing excellent possibilities for the design of effective phosphate mimetics. Especially successful so far seem to be approaches for the synthesis of trisphosphonate-modified nucleotides and nucleosides, which represent a promising class of potential drugs [8

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

• crystallography. Finally, action of ammonia on benzylated 3-N-(galactosyl)oxadiazolinethione unexpectedly yielded 3-N-(galactosyl)triazolinethione. This represents a new path to the conversion of glycosyloxadiazolinethiones to new glycosyltriazolinethione nucleosides, which was until now unknown. Keywords

• : glycosyloxadiazolinethiones; glycosylsulfanyloxadiazoles; glycosylthiosemicarbazides; thermal rearrangement; X-ray crystallography; Introduction Modified nucleosides are versatile motifs for studying the relationship between the structure and functions of nucleic acids and problems of metabolism, besides their main

• 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

• stage was now set for a two-step modification of the phosphonate moiety. Reaction of 8 with lithium azide in hot DMF, under conditions developed for the monodealkylation of phosphonic acid dialkyl esters of nucleosides [19], provided the novel monoethyl ester 9 in 87% yield following purification by a

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

Recyclable fluorous cinchona alkaloid ester as a chiral promoter for asymmetric fluorination of β-ketoesters

• Wen-Bin Yi,
• Xin Huang,
• Zijuan Zhang,
• Dian-Rong Zhu,
• Chun Cai and
• Wei Zhang

Beilstein J. Org. Chem. 2012, 8, 1233–1240, doi:10.3762/bjoc.8.138

• . Introducing one or a few fluorine atoms to biologically interesting molecules can significantly change the physical, chemical and biological properties [1][2]. The significant amount of publications on fluorinated small molecules, amino acids, carbohydrates, steroids and nucleosides indicates that

The effect of the formyl group position upon asymmetric isomeric diarylethenes bearing a naphthalene moiety

• Renjie Wang,
• Shouzhi Pu,
• Gang Liu and
• Shiqiang Cui

Beilstein J. Org. Chem. 2012, 8, 1018–1026, doi:10.3762/bjoc.8.114

• nucleosides and molecular recognition properties of nucleic acids with the light sensitivity of diarylethenes [34]. Recently, Wu et al. designed and synthesized a novel diarylethene-containing dithiazolethene, which exhibited a gated photochromic reactivity controlled by complexation/dissociation with BF3 [35

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

• photochromic nucleosides. All nucleosides were characterized with respect to their absorption and photochromic properties. Based on these results, the most promising photochromic DNA base modification was incorporated into representative oligonucleotides by using automated phosphoramidite chemistry. The

• photoswitchable components in nucleic acids and are suitable for the control of a variety of different biological functions. The photoinduced cis–trans isomerization of azobenzene nucleosides can reversibly switch between the formation and dissociation of DNA duplexes [14][15][16][17], photoregulate DNA

• [29][30], into oligonucleotides (Scheme 1). Although the spiropyran DNA building blocks 1 and 2 exhibit promising photochromic properties as nucleosides, it is not worth pursuing this synthetic direction further for the following reasons [30]: (i) It is reported that spiropyrans decompose in aqueous

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

• ligand-exchange enantioselectivity of [V·H·amph]+ is determined by the effects of the chiral resorcin[4]arene scaffold upon the transition-state structures involved in the reaction, similarly to the complex of V with catharanthine. Rigid resorcin[4]arenes as chiral selectors of nucleosides. Nucleosides

• nucleosides can be an inspiration for both the design of new drug carriers, characterized by high solubility and selectivity, and a better understanding of the selective uptake of nucleosides by their respective membrane receptors [55]. The selected pyrimidine nucleosides are reported in Figure 8, i.e., 2

• resorcin[4]arene coordinating to B (k2). The 1011k1/k−1 and k−1/k2 ratios are reported in Table 3. The basicity of the nucleosides decreases in the order: dC < CT = Cy < GC, and in the same order the 1011k1/k−1 ratio tends to increase, most probably because the partial positive charge on the host pendants

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

• 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

• performed with fully TBDMS-protected ribofuranose nucleosides to allow better regiochemical control and to prevent nucleophilic attack of the base on the sugar moiety [48]. Conclusion In summary, a straightforward approach to 6-ω-alkenyluridines 3 from readily available protected uridine 1 is proposed

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

• . Synthesis Synthesis of alkoxy-haloalkyl derivatives The most numerous and also the most investigated group of the above mentioned derivatives is a group of alkoxy-haloalkyl compounds derived either from uracil or nucleosides (Figure 2). With regard to the high variability of sugar moiety, the description of

• all the compounds is divided into sections according to the nature of the furanose present. 2'-Deoxyuridine analogues: The earliest article describing 2'-deoxyuridine analogues was focused on uracil analogues modified at position 5 by a fluorine containing moiety [6]. Bases or nucleosides substituted

Systematic investigations on the reduction of 4-aryl-4-oxoesters to 1-aryl-1,4-butanediols with methanolic sodium borohydride

• Subrata Kumar Chaudhuri,
• Manabendra Saha,
• Amit Saha and
• Sanjay Bhar

Beilstein J. Org. Chem. 2010, 6, 748–755, doi:10.3762/bjoc.6.94

• LiAlH4 which also often gives rise to several non-identifiable by-products. Structurally varied 1-aryl-1,4-butanediols are of great synthetic value with immense applications in cationic polymerizations [34], as intermediates for the syntheses of important acyclic antiviral nucleosides [35] and cyclic

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

• Abstract The syntheses of novel hydrazono acyclic nucleosides similar to miconazole scaffolds are described. In this series of acyclic nucleosides, pyrimidine as well as purine and other azole derivatives replaced the imidazole function in miconazole and the ether group was replaced with a hydrazone moiety

• 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

• . Moreover, antitumor and antiviral activities of various hydrazone derivatives of nucleosides have also been reported [16][17][18]. Inspired by the miconazole scaffold and also as an extension of our ongoing research in the design and synthesis of novel acyclic nucleosides [19][20][21][22][23][24][25

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

• nanofibres. Keywords: amides; antiprotozoal agents; coupling; nucleosides; self-assembly; Introduction There are numerous reports on the synthesis and application of symmetrical and unsymmetrical α,ω-nucleobase amide-conjugated systems (Figure 1) [1][2][3][4][5][6]. These molecules are constructed usually

• ,ω-nucleobase bolaamphiphiles (VII), capable of forming extraordinary nanotopologies [6]. In order to synthesise a new group of modified, mainly pyrimidinic nucleosides, we employed a simple and effective synthetic pathway based on the catalytic aminolysis of carboxylic acids. Our synthetic approach

• synthesis of N-Boc monoprotected amine reactant 17 (See Supporting Information File 1). The compounds in this second group were obtained in yields of 31–95%. The synthesis of nucleosides containing aliphatic linkages (19–22) presented no difficulties on work-up. Two different acidic and three different