Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• chemotherapeutic agents used for the treatment of cancer were nucleoside analogues and nucleobases [10]. Azidothymidine (1, AZT) was the first approved drug for the treatment of human immunodeficiency virus (HIV) [11][12]. Subsequently, a large number of sugar modified nucleosides, such as ddC (zalcitabine) [13

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• Academy of Higher Education, Manipal-576104, Karnataka, India 10.3762/bjoc.17.182 Abstract Sugar-modified nucleosides have gained considerable attention in the scientific community, either for use as molecular probes or as therapeutic agents. When the methylene group of the ribose ring is replaced with a

• to establish synthetic approaches toward single desired isomers. The methodologies for modified nucleosides are also known as linear approach and convergent approach [3]. We recognized that there are three major obstacles that have to be cleared: i) efficient preparation of the oxathiolane sugar ring

• undesired isomers. Over the past three decades, several research groups have been working on devising novel methods for installing glycosidic linkages during the synthesis of modified nucleosides. For 1,3-oxathiolane nucleosides, to achieve β-selective glycosylation, a certain key intermediate was employed

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• methodologies and the biological applications of double-headed nucleosides. Keywords: acyclic double-headed nucleosides; bicyclic double-headed nucleosides; furanosyl double-headed nucleosides; modified nucleosides; pyranosyl double-headed nucleosides; Introduction Nucleosides are the constructional subunits

• monomeric units polymerize to construct nucleic acids (DNA or RNA). These macromolecules preserve and express genetic information in all living cells and viruses. Modified nucleosides are a class of organic compounds which are unnatural and have an altered/substituted nucleobase and/or a modified pentose

• sugar [3][4]. The synthetic accessibility of these organic molecules encouraged researchers to prepare sugar-modified nucleosides [5][6] and nucleobase-modified nucleosides [7][8]. Modified nucleoside monomers comprising more than one nucleobase are called double-headed nucleosides [9][10]. A thorough

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• diseases. Oligonucleotides with alterations to their scaffold, prepared with modified nucleosides and solid-phase synthesis, have yielded molecules with interesting biophysical properties that bind to their targets and are tolerated by the cellular machinery to elicit a therapeutic outcome. Structural

• acids (BNA) Locked nucleic acids are a class of modified nucleosides which traditionally involve the incorporation of a methylene bridge between C4' and O2' of the ribose sugar (Figure 7A). This incorporation, as first reported by both Wengel and Obika, locks the nucleoside in the C3'-endo (north

• overall steps [164]. ASOs containing these modified nucleosides have demonstrated promising antitumor activity for lymphoma and lung cancer [165]. Numerous other LNA analogues have been constructed including, but not limited to, 2'-N-guanidino,4'-C-ethylene (GENA) (Figure 7I) [166], sulfonamide-bridged

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• with the 3’-OH group, due its higher acidity [29]. For modified nucleosides, the preference of 2’-O-TBDMS formation in the presence of AgNO3 may not be given [29], and indeed, as already mentioned above, the C8-linker conjugated nucleoside derivative 7 (Scheme 1) shows the opposite behavior: the 3’-O

Anion exchange resins in phosphate form as versatile carriers for the reactions catalyzed by nucleoside phosphorylases

• Julia N. Artsemyeva,
• Ekaterina A. Remeeva,
• Tatiana N. Buravskaya,
• Irina D. Konstantinova,
• Roman S. Esipov,
• Anatoly I. Miroshnikov,
• Natalia M. Litvinko and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2020, 16, 2607–2622, doi:10.3762/bjoc.16.212

• -modified nucleosides were obtained in good yields. In spite of the obvious progress in using the transglycosylation reaction for the synthesis of biologically important nucleosides, the idea of researching and developing an effective method for the enzymatic or chemoenzymatic synthesis of PF-1Pis has again

Extension of the 5-alkynyluridine side chain via C–C-bond formation in modified organometallic nucleosides using the Nicholas reaction

• Renata Kaczmarek,
• Dariusz Korczyński,
• James R. Green and
• Roman Dembinski

Beilstein J. Org. Chem. 2020, 16, 1–8, doi:10.3762/bjoc.16.1

• -nucleosides, preserving the dicobalt hexacarbonyl unit. This methodology allows for access in a divergent fashion to a variety of modified nucleosides with potential biological activity, and was shown to be viable for both 2'-deoxy- and regular uridines. Experimental General and instrumentation. All NMR

Synthesis, biophysical properties, and RNase H activity of 6’-difluoro[4.3.0]bicyclo-DNA

• Sibylle Frei,
• Adam K. Katolik and
• Christian J. Leumann

Beilstein J. Org. Chem. 2019, 15, 79–88, doi:10.3762/bjoc.15.9

• conducted. This experiment revealed that the oligonucleotide containing five modified units was able to elicit the RNase H-mediated cleavage of the complementary RNA strand. Keywords: DNA/RNA affinity; fluorinated cyclopropanes; fluorinated nucleic acids; RNase H activity; sugar modified nucleosides

6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

• Sibylle Frei,
• Andrei Istrate and
• Christian J. Leumann

Beilstein J. Org. Chem. 2018, 14, 3088–3097, doi:10.3762/bjoc.14.288

• modification might be a substrate for RNase H. Keywords: DNA/RNA affinity; fluorinated cyclopropanes; fluorinated nucleic acids; molecular dynamics simulations; sugar modified nucleosides; Introduction A powerful strategy for the treatment of various disorders like cancer, viral and inherited diseases is the

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• modified nucleosides arise from changes in hydrogen bonding motifs, electronic effects, hydrophobic interactions, acid-base properties and chemical reactivity [25][26][27][28][29][30][31][32][33][34][35][36][37]. One such modification is the change in the nature of the glycosidic bond [29][37]. Although

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• synthesis of modified nucleosides, in particular 8-CF3-2’-deoxyguanosine and 8-CF3-inosine in 39 and 73% yields, respectively [58]. The same copper-free method was applied for the trifluoromethylation of a variety of electron-deficient 4-substituted acetanilides or anilines (Scheme 36). In these reaction

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

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

• , ester protection is preferred for Vorbrüggen glycosylations in nucleoside syntheses. Very recently, ortho-alkynylbenzoate was successfully developed by our group as neighboring participation group to synthesize 2’-modified nucleosides [24], which could be removed smoothly in the presence of gold(I

Investigation of the action of poly(ADP-ribose)-synthesising enzymes on NAD⁺ analogues

• Sarah Wallrodt,
• Edward L. Simpson and
• Andreas Marx

Beilstein J. Org. Chem. 2017, 13, 495–501, doi:10.3762/bjoc.13.49

• allows the selective labelling of poly(ADP-ribose) [17]. As reported, the synthesis of alkyne-modified derivatives 1–4 was previously [16][17][23] accomplished by preparing the respective alkyne-modified nucleosides from common precursors and turning them into their corresponding NAD+ analogues in a two

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

• ’-difluorocytidine has been routinely utilized to treat solid tumors [30]. However, 3’-fluorine-modified nucleosides have not been well-studied because of the challenges associated with the synthesis of modified carbohydrate moieties [31][32][33][34][35]. As a result, 3’-fluoro-6-heterocyclic-substituted purine

• inhibitory activity, but other derivatives did not show detectable activity against the tested tumor cell lines. Antiviral and other biological evaluation of these 3’-fluorine modified nucleosides is in progress and will be reported in due course. Conclusion The 6-chloropurine, 2,6-dichloropurine, and 2

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

• of 5.0–40 μM. The synthesized compounds do not show any antiviral activity. Keywords: antitumor activity; click chemistry; 1,3-dipolar cycloaddition; nucleic acids; 2’-oxa-3’-aza-4’a-carbanucleoside analogs; Introduction Synthetic modified nucleosides are of great interest as potential new lead

• with substituted alkynes. The biological assays indicate that these compounds inhibit the cell proliferation of Vero, BS-C-1, HEp-2, MDCK, and HFF cells by 50% (CC50) at concentrations in the range of 5.0–40.0 μM. No antiviral activity at subtoxic concentrations was observed. 2’-Oxa-3’-aza-modified

• nucleosides and 2’-oxa-3’-aza-modified nucleotides. Triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides. α–β Epimerization. Synthesis of triazolyl isoxazolidinyl-nucleosides 13 and 14. Reagents and conditions: a) Tosyl chloride, TEA, CH2Cl2, rt, 24 h; b) NaI, acetone, reflux, 72 h; c) NaN3, CH3CN/H2O (1:10) in the

Versatile synthesis of amino acid functionalized nucleosides via a domino carboxamidation reaction

• Vicky Gheerardijn,
• Jos Van den Begin and
• Annemieke Madder

Beilstein J. Org. Chem. 2014, 10, 2566–2572, doi:10.3762/bjoc.10.268

• . This was illustrated in previous research in our laboratory where introduction of modified nucleosides on the 2’-position in a DNA double helix resulted in a destabilization of the duplex of 5 °C per modified unit [32]. Although this destabilization depends on many different aspects, such as the type

• carboxamidation procedure for the synthesis of modified nucleosides featuring two extra functional groups. Because hydrolysis of the methyl ester and removal of the t-Boc is performed during the standard cleavage of solid support using NH4OH and benzyl and benzoyl protecting groups can be removed by hydrogenation

• [64], only one extra deprotection step is needed after incorporation. After transformation of the modified nucleosides into the corresponding phosphoramidite building blocks 5, 9 and 13 are amenable to incorporation in nucleic acids through standard DNA synthesis methodology. The described protocol

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

• the introduced terminal thiophosphate [18][19], or by chemical conversion of the 5'-terminal primary OH group into an amine or azide to be used for further conjugation with NHS-esters [20] or with alkynes [21]. Alternatively, natural and modified nucleosides can be attached to the 3'-terminus by the

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

• a productive transition state of the base and 12a. The good substrate properties of the phosphate 12a prompted us to test it in the enzymatic synthesis of base-modified nucleosides 9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-aza-7-deazaguanine (4a; purine numbering) and 9-(2-deoxy-2-fluoro-β-D

• the synthesis of base-modified nucleosides 4a,b and 5a,b (vide supra). However, from our experience in the synthesis of various nucleosides, we know that the enzymatic synthesis of purine and pyrimidine 2′-deoxy-β-D-ribofuranosides is usually most effective, though it does not follow from the data of

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

• 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

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

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

• : 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

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

• 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

• diarylethene-modified nucleoside 4 then continues by cleavage of the TMS protecting group of 11 with K2CO3 in MeOH. Finally, the synthesis is concluded by the Sonogashira-type coupling of diarylethene 13 to 5-iodo-2’-deoxyuridine (14) in 65% yield. For the second and third modified nucleosides 5 and 6, the

• % yield. Photochromic properties of diarylethene-modified 2’-deoxyuridines 4–6 The photochromic properties of the modified nucleosides 4–6 were characterized by UV–vis absorption spectroscopy at rt. All irradiations for photoswitching of the nucleosides were performed by using a 75 W Xe arc lamp equipped

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

• starting compounds for preparation of modified nucleosides are azidonucleosides. In general, organic azides are valuable, energy-rich and flexible intermediates, which can react very differently under various reaction conditions. [13] They can react at N1 with electrophiles (carbon electrophiles, protons

• desired modified nucleosides 11a-c and 12a-c in good yields (Table 1). 4-Methyl derivatives of the corresponding coumarin-4-acetic acids were only minor byproducts in these reactions. The isolated yields of polar products were negatively influenced by lengthy separation by flash chromatography. The

• new molecule with promising fluorescent and electrochemical properties. The isolated yields of products depend on the structure of azidonucleoside and carboxylic acids. A detailed study of the kinetics of the Staudinger ligation with nucleoside substrates is in progress. Background Modified