A postsynthetically 2’-“clickable” uridine with arabino configuration and its application for fluorescent labeling and imaging of DNA

• Heidi-Kristin Walter,
• Bettina Olshausen,
• Ute Schepers and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2017, 13, 127–137, doi:10.3762/bjoc.13.16

• , 76344 Eggenstein-Leopoldshafen, Germany 10.3762/bjoc.13.16 Abstract The arabino-configured analog of uridine with a propargyl group at the 2’-position was synthesized and incorporated into DNA by solid-phase chemistry. The fluorescence quantum yields of DNA strands that were postsynthetically modified

• DNA polymerases in primer extension experiments and PCR [4][16]. To develop fluorescently labelled oligonucleotides that undergo energy transfer reactions [17] we recently applied 2’-propargyl-modified uridine 1 as DNA building block (Scheme 1) [15][18][19]. A simple look on the three-dimensional

• developed and synthesized the 2’-propargyl-modified arabino-configured uridine analog 2, incorporated it into DNA by automated phosphoramidite chemistry, “clicked” it to a variety of our recently established, photostable cyanine-styryl dyes and probed the fluorescence and energy transfer properties by

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

• , 6-azathymine and 6-aza-2-thiothymine was studied using dG and E. coli purine nucleoside phosphorylase (PNP) for the in situ generation of 2-deoxy-α-D-ribofuranose-1-phosphate (dRib-1P) followed by its coupling with the bases catalyzed by either E. coli thymidine (TP) or uridine (UP) phosphorylases

• ; recombinant E. coli uridine, thymidine and purine nucleoside phosphorylases; substrate properties; 4(2)-thioxo- and 6(5)-aza-uacil and -thymine; Introduction Nucleosides of 4- and 2-thioxopyrimidines and 6-azapyrimidines attract much attention from the time of pioneering works in the early 1950s on the

• investigate the enzymatic transformations of 2(4)-thioxo- and 6(5)-azapyrimidines and their nucleosides in more detail and to outline (i) the scope and limitations of the enzymatic synthesis of 2'-deoxy-β-D-ribonucleosides catalyzed by the recombinant E. coli uridine (UP; EC 2.4.2.3) and thymidine (TP; EC

Tunable microwave-assisted method for the solvent-free and catalyst-free peracetylation of natural products

• Manuela Oliverio,
• Paola Costanzo,
• Monica Nardi,
• Carla Calandruccio,
• Raffaele Salerno and
• Antonio Procopio

Beilstein J. Org. Chem. 2016, 12, 2222–2233, doi:10.3762/bjoc.12.214

• ester (8), uridine (12) and methyl-α-D-glucopyranoside (11)) and natural antioxidant compounds in their simple (hydroxytyrosol (4), homovanillic alcohol (5), quercetin (13)) or glycosylated forms (oleuropein (14), rutin (17), alpha-hederin (16)). Because of their heterogeneity in terms of

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• natural products. These uridine-derived nucleoside-peptide antibiotics inhibit the bacterial membrane protein translocase I (MraY), a key enzyme in the intracellular part of peptidoglycan biosynthesis. This review describes the structures of naturally occurring muraymycins, their mode of action, synthetic

• replication and folate metabolism [21]. Promising candidates meeting the requirements for new drugs are nucleoside antibiotics, i.e., uridine-derived compounds that address the enzyme translocase I (MraY) as a novel target, thereby interfering with a membrane-associated intracellular step of peptidoglycan

• which have a uridine-derived core structure in common. Their antibiotic potency is based on the inhibition of MraY, thereby blocking a membrane-associated intracellular step of bacterial cell-wall biosynthesis. The structure elucidation was carried out using one- and two-dimensional NMR experiments as

Mycothiol synthesis by an anomerization reaction through endocyclic cleavage

• Shino Manabe and
• Yukishige Ito

Beilstein J. Org. Chem. 2016, 12, 328–333, doi:10.3762/bjoc.12.35

• Gram-negative bacteria. MSH undergoes metal-catalyzed autoxidation more rapidly than glutathione [16]. The biosynthetic pathway of MSH has been well investigated; MSH is synthesized from 1-inositol phosphate and uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) in five steps [15]. It is used by

Towards inhibitors of glycosyltransferases: A novel approach to the synthesis of 3-acetamido-3-deoxy-D-psicofuranose derivatives

• Maroš Bella,
• Miroslav Koóš and
• Chun-Hung Lin

Beilstein J. Org. Chem. 2015, 11, 1547–1552, doi:10.3762/bjoc.11.170

• , the insertion of an N-acetylglucosaminyl moiety (GlcNAc-) into an oligosaccharide chain was identified as the crucial step catalyzed by N-acetylglucosaminyltransferases (GnTs) in the presence of a metal co-factor. In this catalytic reaction, UDP-GlcNAc [uridine 5′-(2-acetamido-2-deoxy-D-glucopyranosyl

Terminal lipophilization of a unique DNA dodecamer by various nucleolipid headgroups: Their incorporation into artificial lipid bilayers and hydrodynamic properties

• Emma Werz and
• Helmut Rosemeyer

Beilstein J. Org. Chem. 2015, 11, 913–929, doi:10.3762/bjoc.11.103

• positions of the pyrimidine β-D-ribonucleosides uridine (1, R = H), 5-methyluridine (2, R = CH3) and 5-fluorouridine (3, R = F) which were lipophilized by different hydrophobic residues. The following formulae (Figure 2) show the six nucleolipids 4a–9a [13][14][15][16][17], which designate that mono

• events (perfusion and incubation time) for the lipo-oligomer 10. As can be seen, the incorporation of the lipo-oligomer 10 carrying an O-2’,3’-undecylidene-modified uridine head group into the artificial lipid bilayer occurs spontaneously after 25 min, corresponding to the maximum brightness. However

• ’-pentatriacontanylidene-modified uridine head group shows a different behavior (Figure 6): the corresponding lipo-oligonucleotide 11 is bound directly after addition into the cis compartment of the sample carrier within the lipid bilayer (5 min). Once bound it exhibits a significantly higher resistance against perfusion

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

• corresponding uridine-derived nucleosyl amino acids, we have found that uracil protection was not advantageous for the aforementioned reaction sequence [48]. We have therefore decided to employ both the 3-(N-BOM)-protected thymidine-5'-aldehyde 10 and also its thymine-unprotected congener 11 in Wittig–Horner

• with methanol), thus providing 3'-O-TBDMS-protected derivatives 15 and 16 in yields of 59% and 66%, respectively. This method turned out to be advantageous compared to 5'-O-desilylation mediated by TFA, which had provided satisfying results in the case of the corresponding uridine derivatives [48]. The

• were applied for the synthesis of uridine-derived nucleosyl amino acids [47][48]. It was therefore possible to direct the stereochemical outcome of the hydrogenation reaction by the choice of either the (S,S)- or the (R,R)-catalyst. As reported previously [38], the hydrogenation of pure 3-(N-BOM

Solution phase synthesis of short oligoribonucleotides on a precipitative tetrapodal support

• Alejandro Gimenez Molina,
• Amit M. Jabgunde,
• Pasi Virta and
• Harri Lönnberg

Beilstein J. Org. Chem. 2014, 10, 2279–2285, doi:10.3762/bjoc.10.237

• derivative 3d partially the dimethylaminomethylene group, yielding 4c' and 4d', respectively. Reintroduction of the same protecting group to 4d' gave the desired 4d in high yield, whereas 4c' was benzoylated to obtain 4c''. In addition, the uridine derivative 3a underwent partial removal of the 3-benzoyl

• immobilization of the 3'-terminal nucleoside to the azido functionalized support, 3-benzoyl-2-O-cyanoethyl-5-(1-methoxy-1-methylethyl)uridine (4a) was transformed to its 3'-O-(4-pentynoyl) derivative 6a. To accomplish this, 4-pentynoic acid was first converted to its anhydride by DCC activation in dioxane and

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

• which no ribozyme analogue has yet been found. This applies for example to the transformation of cytidine to uridine, which is a well-known RNA editing event in modern cellular chemistry [9]. This process is catalyzed by cytidine deaminases (CDA, EC 3.5.4) belonging to a family of enzymes found in pro

• support deamination of cytidine to uridine. For this purpose, a bifunctionalized cytidine derivative (Figure 1) was synthesized. Via its 5'-OH group, the cytidine derivative is linked to a hexaethylene glycol tether bearing a primary amino group. At the C4-position of the base, a short linker connected to

• –streptavidine interaction. All RNA sequences that can catalyze the desired deamination reaction of cytidine to uridine will be cleaved off and thus released into solution. Upon recovery, beneficial variants can be subjected to the next round of selection. Here we describe the synthetic route to the

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

• -leishmanial activity of compounds 30 and 31, as well as their activity against the vaccinia virus or cowpox virus, were evaluated. Several products 30 displayed moderate anti-leishmanial activity in the range of 12–44 µM. The synthesis of the uridine derivative 35 involving the Ugi condensation as the key

• step was successfully accomplished by Tsuchida et al. (Scheme 15) [80]. The isopropylidene-protected 3-(2-formylethyl)uridine 32, 2-(aminomethyl)pyridine 1-oxide, cyclohexenyl isocyanide, and acetic acid were allowed to react under ambient conditions for 24 h to yield the expected product 33. Further

• conventional deprotection and acylation steps afforded the intermediate 34. Upon treatment with 6 N HCl at 80 °C for 2 h the 3-(3-amino-3-carboxypropyl)uridine (35) was obtained in 80% yield. While this nucleoside was found in some transfer RNAs, no details of its application were disclosed. Boehm and

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

• with a representative set of chromophore-modified oligonucleotides and found that the DNA-polymerase-catalyzed nucleotide incorporation opposite to attached chromophores at the 5-position of uridine follows Watson–Crick selectivity [49]. In the meantime, DNA polymerases have been evolved that have an

Coupled chemo(enzymatic) reactions in continuous flow

• Ruslan Yuryev,
• Simon Strompen and
• Andreas Liese

Beilstein J. Org. Chem. 2011, 7, 1449–1467, doi:10.3762/bjoc.7.169

• hexahistidine tags on nickel–agarose beads (“super beads”) [33]. These enzymes catalyze a complex network of sequential and coupled reactions, in which galactose, uridine monophosphate (UMP) and inorganic polyphosphate are converted to uridine diphospate galactose (UDP-Gal) in the presence of catalytic amounts

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

• report herein that sequential ring lithiation/methylation of the simple protected uridine 1 leading to 2 followed by lateral lithiation/alkylation with ω-alkenyl bromides provides a useful regioselective chain-extension procedure and an efficient route to 3. Results and Discussion Most methods for the

• chloroacetone or 2-chloroacetophenone in the presence of LDA (1.2 equiv, THF, −78 °C) afforded 6-(oxiranylmethyl)uridine derivatives 14 exclusively (Figure 3) [29]. With 5-chloro-2-pentanone, the reaction led to a mixture of 5- and 6-substituted uridine regioisomers 15 and 16 in 47% and 28% yield, respectively

• 3-bromocamphor was used as an electrophile. The corresponding C5-alkylated uridine derivative was obtained as the only recovered product, in low yield (23%), besides the unreacted substrate. Having these precedents in mind, we decided to investigate the preparation of 6-ω-alkenyluridines 3 by

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

• derivatives of 2'-deoxyuridine 28, 2'-fluoro-2'-deoxyuridine 29 and uridine 30 (Scheme 4). The authors utilized the known palladium acetate-triphenylphosphine-catalyzed reaction of 5-iodo-2'-deoxyuridine with vinyl acetate for the preparation of 5-vinyl-2'-deoxyuridine (9) [14]. However, attempts to prepare 2

• '-fluoro-2'-deoxyuridine 23 and uridine analogue 24 by this method were unsuccessful. Hence, the 5-vinyl derivatives 9, 23 and 24 were prepared by three-step palladium-catalyzed synthesis of 5-iodo-2'-fluoro-2'-deoxyuridine (15) and 5-iodouridine (16) with ethyl acrylate, followed by subsequent alkaline

• hydrolysis and decarboxylation. Iodination of 5-vinyl analogues 9, 23 and 24 with iodine in the presence of the iodic acid as an oxidizing agent afforded 5-(1-hydroxy-2-iodoethyl)-2'-deoxyuridine (25, 59%), 5-(1-hydroxy-2-iodoethyl)-2'-fluoro-2'-deoxyuridine (26, 72%) and 5-(1-hydroxy-2-iodoethyl)uridine (27

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

• a thiophosphate nucleophile from commonly used bromoacetate ester cross-linking agents. Results: We found cross-linking between uridine-5′-monophosphorothioate and D-glucosamine using N-hydroxybenzotriazole and N-hydroxysuccinimde bromoacetates to be ineffective. In order to gain insight into these

• shortfalls, 2-S-(5′-thiophosphoryluridine)acetic acid esters were prepared using p-nitrophenyl bromoacetate or m-nitrophenyl bromoacetate in combination with uridine-5′-monophosphorothioate. Kinetics of hydrolysis and aminolysis of the resulting p- and m-nitrophenyl 2-S-(5′-thiophosphoryluridine)acetates

• aqueous work-up, the products were 70–99% pure as measured by integration of signals in 1H NMR spectra, and were used without further purification. Uridine-5′-monophosphorothioate 4 was prepared using an adaptation of Whitesides’ procedure for the thiophosphorylation of adenosine [4]. We performed

Bioorthogonal metabolic glycoengineering of human larynx carcinoma (HEp-2) cells targeting sialic acid

• Arne Homann,
• Riaz-ul Qamar,
• Sevnur Serim,
• Petra Dersch and
• Jürgen Seibel

Beilstein J. Org. Chem. 2010, 6, No. 24, doi:10.3762/bjoc.6.24

• and the genetic control of Neu5Ac 1 synthesis by feedback inhibition. The accumulation of Neu5Hex 3 is proposed by incubation of 3 with the target cell line as the synthesis of Neu5Ac 1 is down-regulated [11][13]. UDP: uridine diphosphate; GNE: UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine

Synthesis of coumarin or ferrocene labeled nucleosides via Staudinger ligation

• Ivana Kosiova,
• Andrea Janicova and
• Pavol Kois

Beilstein J. Org. Chem. 2006, 2, No. 23, doi:10.1186/1860-5397-2-23

• . Analogous reaction of 4-ferrocenyl-4-oxobutanoic acid reactive ester with iminophoshorane nucleoside derivative 7 gave 2'-ferrocene labeled uridine (Scheme 3). The yield of pure isolated product 18 was 57% and its structure was confirmed by 1H and 13C NMR, 1H-1H COSY and 13C-1H HSQC analysis. Conclusion We

• labeled nucleosides, (i) PPh3, acetonitrile, (ii) HOBT, DCC, dioxane Hydrolysis of proposed intermediates I(a-c)-IV(a-c) Preparation of ferrocene labeled uridine Isolated yields and spectral characteristics of coumarin labeled nucleosides 11–12 a Supporting Information Supporting Information File 4

The first salen- type ligands derived from 3',5'-diamino- 3',5'-dideoxythymidine and -dideoxyxylothymidine and their corresponding copper(II) complexes

• Daniel Koth,
• Michael Gottschaldt,
• Helmar Görls and
• Karolin Pohle

Beilstein J. Org. Chem. 2006, 2, No. 17, doi:10.1186/1860-5397-2-17

• lot of sugar based complexes have been described already [3][4], so far, the use of the carbohydrate moiety of nucleosides as a binding group in metal complexes has only been known for very few examples. [5][6][7] Previously, we reported the synthesis of a 2',3'-diimino functionalized uridine and its