From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• living cells these pathways associate interconversions between purines and pyrimidines [34][35]. Furthermore, the nitrogen-rich intermediate 5-amino-6-(D-ribitylamino)uracil comprises building blocks that are commonly found under prebiotic conditions. Once phosphorylated (as discussed previously, via

First total synthesis of kipukasin A

• Chuang Li,
• Haixin Ding,
• Zhizhong Ruan,
• Yirong Zhou and
• Qiang Xiao

Beilstein J. Org. Chem. 2017, 13, 855–862, doi:10.3762/bjoc.13.86

• China Sea and the Sea of Okhotsk, respectively. Kipukasins are uridine derivatives with unique structural characteristics, which include: (1) a uracil moiety with or without an N-3 methyl group; (2) a 6-methyl-2,4-hydroxy (or methoxy)-benzoyl group at C-2’ or C-3’ position; (3) with or without an acetyl

• ). Kipukasin A could be constructed by Vorbrüggen glycosylation [22][23] of a properly protected glycosyl donor 3 with uracil (4). Neighboring group participation of the 2’-O-acetyl group stereoselectively facilitate the β-glycosidic bond formation. Thus, the choice of a suitable protecting group at 5-OH

• ) [36]. With glycosylation donor 16 in hand, we proceeded to investigate the crucial Vorbrüggen glycosylation with uracil (4). To our delight, in a similar manner as our described in [17], it proved to be efficient to give nucleoside 17 with exclusive β-configuration in 89% yield. At last, using our

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

• 50% acetonitrile in water)). DNA concentrations were measured by their absorbance in water at 260 nm on a ND-1000 spectrometer from NanoDrop in the nucleic acid mode. Synthesis of 4. 1-Deoxy-1-(uracil-1-yl)-β-D-arabinofuranose (3, 1.00 g; 4.10 mmol) was dried under reduced pressure for 1 h and was

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

• nucleoside obtained in the synthesis. Notably, phosphorolysis of (i) 2'-deoxyuridine (Ud) by UP proceeds at somewhat lower rate, but also reaches an equilibrium point at a similar ratio of uracil-Ud within one hour and then remains practically unchanged, and (ii) thymidine (Td) occurs at a lower rate than Ud

• ) and the role of some amino acid residues of the catalytic site was characterized by the single-site mutagenesis [41]. It was suggested that the uracil binding site includes Gln166, the carboxamide group of which forms two strong hydrogen bonds 3N(H)···(O=)C(R)-NH2···(O=)C-2. Moreover, the carbonyl

• group of the Glu166 side-chain forms an additional hydrogen bond with a water molecule, which, in turn, takes a part in hydrogen bonding to the 4C(=O) oxo function of uracil and to the adjacent guanidinium group of Arg223 [40]. In addition, the side-chain of Arg168 is directly hydrogen-bonded to the 4C

A detailed view on 1,8-cineol biosynthesis by Streptomyces clavuligerus

• Jan Rinkel,
• Patrick Rabe,
• Laura zur Horst and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 2317–2324, doi:10.3762/bjoc.12.225

• cerevisiae FY834 together with linearised vector pYE-Express [32] (EcoRI and HindIII digestion) using the LiOAc/SS carrier DNA protocol [39]. Transformed cells were plated on SM-URA medium (20 g glucose, 1.7 g yeast nitrogen base, 5 g ammonium sulphate, 0.77 g nutritional supplement minus uracil, 24 g agar

Organic chemistry meets polymers, nanoscience, therapeutics and diagnostics

• Vincent M. Rotello

Beilstein J. Org. Chem. 2016, 12, 1638–1646, doi:10.3762/bjoc.12.161

• research really became interesting when we started mixing multivalent complementary polymers together. When we mixed together diaminopyridine and uracil polymers together in chloroform we generated a turbid solution. Under the microscope we found that the turbidity surprisingly arose from vesicular

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

• griseoflavus subsp. thuringiensis [29][30][31]) and corynetoxins (isolated in 1981 from Corynebacterium rathayi [32]). These classes have merely the uracil nucleoside core structure in common with the muraymycins and the terminally branched lipophilic side chain resembles the acyl moiety in muraymycins of

• group B. Capuramycin, a nucleoside antibiotic isolated in 1986 from Streptomyces griseus, shares the uracil-derived nucleoside moiety with the muraymycins [33][34]. The antibiotic FR-900493, which is structurally closely related to muraymycins, was isolated from Bacillus cereus and characterised in 1990

• E. faecalis, but also against some Gram-negative E. coli strains [49]. Tunicamycin, capuramycin and FR-900493 only show antimicrobial activity against Gram-positive strains. For mureidomycin C (R5 = Gly, AA2 = AA5 = m-Tyr, AA4 = Met, B = uracil, see Figure 2) as a representative compound, no

Versatile synthesis and biological evaluation of novel 3’-fluorinated purine nucleosides

• Hang Ren,
• Haoyun An,
• Paul J. Hatala,
• William C. Stevens Jr,
• Jingchao Tao and
• Baicheng He

Beilstein J. Org. Chem. 2015, 11, 2509–2520, doi:10.3762/bjoc.11.272

• ]. Design and synthesis of purine-based nucleosides are still needed to enable new therapies for the treatment of drug-resistant tumors and viruses. One of the first antimetabolite drugs rationally designed from biochemical data was 5-fluorouracil. A hydrogen atom on uracil was replaced with a fluorine atom

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

• .11.146 Abstract An intramolecular dehydrogenative C–H activation enabled an efficient synthesis of an uracil-annulated β-carbolinone ring system. The reaction is simple, efficient and high yielding (85–92%). Keywords: β-carbolinones; cyclization; dehydrogenative C–H activation; Pd(OAc)2; uracil

• 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

• -fluorouracil [20] and other uracil-based molecules [21][22][23] such as 3’-azido-3’-deoxythymidine (AZT), 2’,3’-dideoxycytidine (DDC), (E)-5-[2-(bromovinyl)-2’-deoxyuridine] (BVDU), are active against cancer and the HI virus [24][25][26][27][28][29][30][31]. Diverse approaches towards the synthesis of β

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

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

• as Mannich bases) can serve as starting materials in the syntheses of a variety of compounds. The employment of a nucleoside as the hydrogen active component has been one of the most common variants of the Mannich reaction. Treatment of uracil (or 2-thiouracil) nucleosides 1 with aq formaldehyde and

• non-nucleoside substrates (Schemes 7–9). Filichev et al. used pyrrolidine 16, paraformaldehyde and uracil for the preparation of the Mannich base 17, which is considered as an 1'-aza-analog of pseudouridine (Scheme 7) [66]. Information on application of compound 17 was not given. By employing

• substrate afforded nucleosides 30 bearing a N-acyl α-amino acid amide moiety at the uracil C-5 carbon atom (Scheme 14) [79]. The variant of the reaction with trimethylsilyl azide (TMS-N3) in place of the carboxylic acid gave the tetrazole-substituted nucleosides 31 [79]. Products 30 and 31 were obtained as

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

• Table 3 for dRibo-1P. Obviously, the effectiveness of nucleoside synthesis is controlled by several factors, and the role of each of these factors depends on the substrate structure. The most unexpected finding is that E. coli UP and TP are not able to catalyze the condensation of uracil and thymine

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

• properties. PNA fluorescent probes bearing pyrene units as “universal base” were described [31][32], and recently, pyrrolidinyl-PNA bearing a uracil-linker pyrene unit showed good fluorescence response and mismatch recognition [33]; though terminal pyrene units were shown to stabilize triplexes formed by

• oligonucleotide probes [34], the effect of single- or multiple pyrene units on PNA in the formation of triplex structures has still to be addressed. We have recently reported the modification of uracil at C5 by hydroxymethylation, followed by substitution with chloride and then with azide, which can be used for

• , electronic or steric, which affect both self-aggregation of the PNA and their interactions with complementary DNA strand. Substitution at the C-5 position of the uracil ring allows positioning of the substituent in the direction of the major groove of the double helix, thus reducing the destabilization

Synthesis, characterization and DNA interaction studies of new triptycene derivatives

• Sourav Chakraborty,
• Snehasish Mondal,
• Rina Kumari,
• Sourav Bhowmick,
• Prolay Das and
• Neeladri Das

Beilstein J. Org. Chem. 2014, 10, 1290–1298, doi:10.3762/bjoc.10.130

• generated when a purine (A/G) or a pyrimidine (C/T) base is stripped off from the DNA strand and this is considered as the most common type of DNA damage lesions. We generated one abasic site in a 48-base pair long oligomer duplex by treating the DNA (Figure 3) with Uracil DNA Glycosylase (UDG) enzyme

• , which excises one uracil residue present in the middle of the oligomer duplex (Figure 3). The oligomer duplexes after UDG treatment were incubated with 200 µM of the compound (1–8) for 24 hours in 10 µL reaction mixture. We found that none of the compounds were able to generate single strand breaks at

• : pUC19 plasmid, Uracil DNA Glycosylase (UDG) enzyme, APE1 enzyme, BamHI, and HindIII restriction endonucleases were purchased from New England Biolabs (USA). HPLC-purified monouracil-containing synthetic deoxyoligomers were purchased from Sigma-Aldrich and deoxyoligomer concentrations were adjusted as

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

• dependence of the thermal stability of complementary complexes formed by the MorGly oligomers on the heterocyclic base composition (uracil or adenine) of the modified chain. It was shown while studying their tandem complexes that the impact of cooperative interactions at oligomer junctions on the thermal

• 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

• 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

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• as the major products. F. Minisci and coworkers also obtained similar results when using a catalytic iron(III) salt in the presence of tert-butyl peroxide as oxidant. T. Yamakawa et al. applied this Fenton-based generation of perfluoroalkyl radicals for the trifluoromethylation of uracil derivatives

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

• preparation of substituted pyridines. Many antiviral agents show a close structural resemblance to the nucleotides uracil, thymine and cytosine. Lamivudine (3.1) or zidovudine (3.2) are typical examples of pyrimidines/pyrimidones bound to a ribose-analogue (Figure 9) [83]. These molecules function by

• terminating biosynthesis of nucleic acids eventually interrupting the division of virally infected cells. Most commonly the pyrimidine/pyrimidone substructure has been introduced as a preassembled unit. Thymine (3.3), cytosine (3.4) and uracil (3.5) are all industrially accessed on large scale utilising

• various robust routes (Scheme 31) [84][85]. Most of these transformations use condensation reactions between urea (3.6) and a bis-electrophile to generate the desired structures. For instance, ester 3.7 furnishes uracil (3.5), which in turn can be converted into cytosine (3.4) by selective amination with

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 monochromator for wavelength-selective excitation. The absorption of nucleoside 4 in the pure synthetic form (and presumably open form) shows absorption peaks in the UV range at 242 nm and 310 nm (Figure 1A). It is assumed that the band at 242 nm overlays with the absorption of the uracil moiety

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• responsible for uracil ring formation, although biochemical evidence is currently missing. The final hydroxylation step towards cylindrospermopsin has been shown to be catalyzed by CyrI, a 2-oxoglutarate-dependent iron oxygenase [31]. Interestingly, two epimers were described for the corresponding hydroxyl

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

• specific and much less toxic for organisms. One of those groups of investigated derivatives is a group of uracil analogues modified at the 5 position by an ether or ester moiety. Since a vast number of C-5 modified pyrimidine analogues are known, this review is focused on a group of selected compounds with

• . 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

Heavy atom effects in the Paternò–Büchi reaction of pyrimidine derivatives with 4,4’-disubstituted benzophenones

• Feng-Feng Kong,
• Jian-Bo Wang and
• Qin-Hua Song

Beilstein J. Org. Chem. 2011, 7, 113–118, doi:10.3762/bjoc.7.16

• less efficient Paternò–Büchi reaction. Experimental Materials 1,3-Dimethylthymine (DMT) and 1,3-dimethyluracil (DMU) were was prepared from thymine and uracil, respectively. 4,4’-Dimethoxybenzophenone, 4,4’-dichlorobenzophenone, 4,4’-dibromobenzophenone and 4,4’-dicyanobenzophenone were prepared

Synthesis of a novel analogue of DPP-4 inhibitor Alogliptin: Introduction of a spirocyclic moiety on the piperidine ring

• Arumugam Kodimuthali,
• Padala Lakshmi Prasunamba and
• Manojit Pal

Beilstein J. Org. Chem. 2010, 6, No. 71, doi:10.3762/bjoc.6.71

• compound C indicates that the key step would involve the condensation of two key intermediates, i.e., the piperidinyl derivative 9 and the appropriately substituted 6-chloro uracil derivative 11 (Figure 2). The intermediate 9 in turn could be synthesized via functional group manipulations of the spiro

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

• via amide bond(s) from two subunits containing nucleobases or their analogues (B1, B2) bearing various linkages (A1, A2). We have previously reported compounds containing 5-substituted uracil-1-yl subunits bound via short (I, II) or extra-short (III) amide-linkages [1]. These compounds exhibited

• against it within the group tested. Very recently, Accetta et al. reported remarkable symmetrical amide-conjugated bis-α,ω-uracil based systems (IV). These compounds exhibited antiproliferative and erythroid differentiation induction properties towards human chronic myelogenous leukaemia K562 cells [3

• groups were obtained by acidic hydrolysis of N-1 Michael adducts of uracils or N-9 Michael adducts of 6-chloropurine with methyl acrylate (Scheme 1A) [1]. Uracil derivatives were obtained via the fully regioselective one-step procedure as previously reported [11][12]. To construct systems containing

Synthesis of some novel annulated pyrido[2,3-d]pyrimidines via stereoselective intramolecular hetero Diels–Alder reactions of 1-oxa-1,3-butadienes

• Mohit L. Deb and
• Pulak J. Bhuyan

Beilstein J. Org. Chem. 2010, 6, No. 11, doi:10.3762/bjoc.6.11

• Diels–Alder reactions involving 1-oxa-1,3-butadienes. Keywords: β-halo aldehydes; hetero Diels–Alder reaction; 1-oxa-1,3-butadiene; pyrido[2,3-d]pyrimidines; uracil; Introduction The importance of uracil and its annulated derivatives is well recognized by synthetic as well as biological chemists [1][2

• ], antihypertensive [13], bronchiodilator [15] and vasodilator [16] properties. Additionally, some compounds of this type exhibit antialergic [17], antimalarial [18], analgesic [19][20] and antifungal [21] activity. Consequently, much effort has been directed towards the synthetic manipulation of uracil for the

• complex annulated pyrido[2,3-d]pyrimidines by intramolecular hetero Diels–Alder reactions involving 1-oxa-1,3-butadienes (Scheme 1). The key intermediate, the 2-chloro-3-formyl uracil derivative 1 (β-halo aldehyde), was prepared by the reaction of N,N-dimethyl barbituric acid with Vielsmeier reagent (DMF

N-1 regioselective Michael- type addition of 5-substituted uracils to (2-hydroxyethyl) acrylate

• Sławomir Boncel,
• Dominika Osyda and
• Krzysztof Z. Walczak

Beilstein J. Org. Chem. 2007, 3, No. 40, doi:10.1186/1860-5397-3-40

• -hydroxyethyl) acrylate is presented. The reactions were performed in polar aprotic solvents and with avoidance of polymerization of acrylic substrate. The obtained adducts may serve as versatile substrates for further functionalization, e.g. into (3-uracil-1-yl)propanoic acids or transformations, with

• against numerous DNA-viruses.[5] One of the most convenient methods of uracil ring N-alkylation is the Michael-type addition. Other general ways of alkylation are: nucleophilic substitution of halogenoalkyl substrates by activated uracil rings (in the N-anionic or O-persililated derivatives);[6][7

• ] Mitsunobu reaction;[8] or reactions that operate through ANRORC-mechanisms that require the presence of strongly electron-withdrawing groups.[9] Recently, we have described an N1- and N3-regioselective Michael-type addition of 5-substituted uracil derivatives to methyl acrylate and acrylonitrile.[10