1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• context, 1,4-dithianes can thus also be considered as synthetic equivalents of cyclohexanes. Oxidative decoration of the carbon atoms in the dithiane ring can also be achieved via Pummerer-type chemistry, as illustrated by Pallumbo’s racemic synthesis of the dihydrodithiin-based nucleoside analog 135 via

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• excellent route for the efficient and cost-effective preparation of different building blocks including nucleoside derivatives and ʟ-pipecolic acid. High efficiency was achieved with simple trapping columns downstream of the biocatalytic process, to separate the pure products from the mixture and

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• nitration. A further strength of our route is divergency, additionally enabling the synthesis of 1-deazahypoxanthine (c1I base). Keywords: deazapurine; heterocycles; imidazopyridines; nucleoside; nucleotides; pyrrolopyrimidines; RNA atomic mutagenesis; Introduction Deazapurines (imidazopyridines and

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling

• Elenilson F. da Silva,
• Krist Helen Antunes Fernandes,
• Denise Diedrich,
• Jessica Gotardi,
• Marcia Silvana Freire Franco,
• Carlos Henrique Tomich de Paula da Silva,
• Ana Paula Duarte de Souza and
• Simone Cristina Baggio Gnoatto

Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161

• , University of São Paulo, Ribeirão Preto, SP 14040-020, Brazil 10.3762/bjoc.18.161 Abstract Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infections in infants. Currently, ribavirin, a nucleoside analog containing a 1,2,4-triazole-3-carboxamide moiety, is a first-line

• with COVID-19 precautions; however, they state that less RSV cases now could reduce immunity and they fear there will be a rebound in infections after the pandemic [4][5][6][7]. As a therapeutic resource, ribavirin, a nucleoside analog prodrug containing a 1,2,4-triazole-3-carboxamide moiety (RBV

Make or break: the thermodynamic equilibrium of polyphosphate kinase-catalysed reactions

• Michael Keppler,
• Sandra Moser,
• Henning J. Jessen,
• Christoph Held and
• Jennifer N. Andexer

Beilstein J. Org. Chem. 2022, 18, 1278–1288, doi:10.3762/bjoc.18.134

• side reactivity of PPK2 enzymes [22]. An alternative explanation might be the PPK equilibrium: most PPKs accept a broad range of nucleoside substrates, therefore some 2-Cl-dATP produced could be a substrate for a PPK2 catalysed 2-Cl-dATP/2-Cl-dADP equilibrium. Conclusion PPK2, and also PPK1 enzymes are

• `-monophosphate (5F-UMP). The phosphorylation of the NMP is catalysed by the ATP dependent nucleoside monophosphate kinase yielding a 5F-UDP and ADP. 5F-UDP is then phosphorylated by pyruvate kinase under consumption of phosphoenol pyruvate [42]. c) Ranking of different phosphate donors that can be used for ATP

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• using CPD as a precursor for high value-added fine chemicals such as a homocitric acid lactone was published by our group [19]. Since then we have developed synthetic pathways for lycoperdic acid [20] and nucleoside analogues [21] starting from CPD. The organocatalytic methods for the synthesis of

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

• -glucofuranose following chemoenzymatic and chemical routes in 34–35% and 24–25% overall yields, respectively. The quantitative and diastereoselective acetylation of primary hydroxy over two secondary hydroxy groups present in the key nucleoside precursor was mediated with Lipozyme® TL IM in 2

• acetylation; Introduction In the last few decades, modification of nucleoside/nucleotide analogues has been a field of keen interest to researchers due to their therapeutic properties for treatment of cancer, viral and microbial infections [1][2][3][4][5][6][7][8][9]. The very first cytotoxic

• 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

• sulfur atom at the 3’-position, these compounds have proved to be structurally potent nucleoside analogues, and the best example is BCH-189. The majority of methods traditionally involves the chemical modification of nucleoside structures. It requires the creation of artificial sugars, which is

• -oxathiolane ring with different nucleobases in a way that only one isomer is produced in a stereoselective manner via N-glycosylation. An emphasis has been placed on the C–N-glycosidic bond constructed during the formation of the nucleoside analogue. The third focus is on the separation of enantiomers of 1,3

• -oxathiolane nucleosides via resolution methods. The chemical as well as enzymatic procedures are reviewed and segregated in this review for effective synthesis of 1,3-oxathiolane nucleoside analogues. Keywords: chiral auxiliaries; enzymes; Lewis acids; N-glycosylation; 1,3-oxathiolane sugar and nucleosides

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• [46]. A similar type of reaction methodology was employed for the formation of a bicyclic nucleoside analog. 4'-C-vinylribofuranoside derivative 21 on treatment with Hg(TFA)2 followed by reduction with NaBH4 leads to the formation of bicyclic nucleoside derivative 22 (Scheme 10) [49]. Pyrrolidine and

• . Synthesis of β-ᴅ-arabinose derivative 18. Hg(OAc)2-mediated synthesis of tetrahydrofuran derivatives. Synthesis of Hg(TFA)2-mediated bicyclic nucleoside derivative. Synthesis of pyrrolidine and piperidine derivatives. HgCl2-mediated synthesis of diastereomeric pyrrolidine derivatives. HgCl2-mediated

Synthesis of O⁶-alkylated preQ₁ derivatives

• Laurin Flemmich,
• Sarah Moreno and
• Ronald Micura

Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147

• in the biosynthetic pathway of the hypermodified tRNA nucleoside queuosine (Q) (Scheme 1) [5]. The core structure of the nucleobase is 7-aminomethyl-7-deazaguanine, a pyrrolo[2,3-d]pyrimidine also termed prequeuosine base (preQ1) [6][7]. In many bacteria, preQ1 binds to specific mRNA domains and

• )), 150.7 (C(4)), 120.0 (C(8)), 116.3 (q, JCF = 295.0 Hz, CF3COO−), 107.5 & 96.2 ((C(5) & C(7)), 53.7 (H3CO), 34.8 (CH2CC(7)) ppm; ESIMS (m/z): [M + H – NH3]+ calcd, 177.0771; found, 177.0767; [M + H]+ calcd, 194.1036; found, 194.1032. Chemical structures of queuine (Q base) and the hypermodified nucleoside

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

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• (poly)amine groups via the nucleobase on ASOs, thereby improving the RNA-binding affinity [26]. This strategy can be employed either on the nucleoside level, which requires many different nucleotide building blocks to be synthesized or via the so-called post-synthetic modification strategy of ONs. The

• -iodo-modified nucleobase/nucleoside followed, if desired, by reduction [44] to give a more flexible group, or the alkyne group can be retained, depending on the modification needed [45][46][47]. This method has been extensively used to study various modifications, and some of them can be seen in Table

• between the modified nucleobase and the corresponding guanidine, which resulted in an increase in Tm of 16 °C, i.e., in the same range as obtained with the original G-clamp (Table 3A) [59]. Generally, conversions of nucleoside phosphoramidite synthons have been explored only rarely. However, the

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• ]. Based on an initial optimization study, manganese(I) pentacarbonyl bromide was deemed as the optimal catalyst, enabling a robust racemization-free allylation process. In addition to tryptophan-containing peptides, diazepam and nucleoside analogues were found to be viable allylation substrates, affording

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

• , Bose Institute, P1/12 CIT Scheme VIIM, Kolkata-700 054, India 10.3762/bjoc.17.98 Abstract Double-headed nucleoside monomers have immense applications for studying secondary nucleic acid structures. They are also well-known as antimicrobial agents. This review article accounts for the synthetic

• 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

• terminal carbons only. Double-headed nucleosides are synthetically derived nucleoside scaffolds that are known to impact significantly secondary structures in nucleic acids [29]. Some oligonucleotides containing a particular double-headed nucleotide monomer have been found to form a three-way junction

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• -nucleoside reverse transcriptase inhibitor (NNRTI) doravirine (49) in flow (Scheme 5) [100]. The aldol reaction of an aromatic ester 44 with a vinylogous ester 45 was achieved in a continuous manner, yielding the hydroxyl adduct, 46, in 85% yield within just a 15 second residence time. Here, a slightly

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

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

• synthesize the nucleoside dimer phosphoramidite with the appropriate amide linkage, which can then be introduced into the strand by solid-phase synthesis. These dimers are synthesized by using an amide coupling reagent to condense a 3'-carboxylic acid nucleoside with a 5'-amine nucleoside, where the

• obtained through condensation with N,N-dicyclohexylcarbodiimide (DCC) giving rise to homopolymeric tetramers of either G-GNA or T-GNA [97]. In 1996, Acevedo and Andrews were the first to demonstrate the synthesis of GNA nucleoside phosphoramidite derivatives as well as the ability of the phosphoramidite

• aluminum 2-methoxyethoxide, which attacks and inserts at the 2'-position, opening the ring and producing the nucleoside with the correct stereochemistry (Scheme 5) [117]. Conveniently, this 2'-O-MOE uridine can be converted to the cytidine derivative by 4-nitrophenylation, 3',5'-trimethylsilylation and

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• temperatures to be completed. Among the widely studied 1,2,3-triazolyl nucleoside conjugates [57][58], the synthesis of 2-triazolylpurine derivatives containing a designed substituent at C6 has been little discussed. 6-N-Substituted purines have been the most studied [11][59][60][61][62], but 6-S- [14][63] or

• ) were inert in SNAr reactions with 2,6-bistriazolylpurines and their attempted reactions resulted in an unidentifiable mixture of byproducts. The following experiments were performed on 2,6-bistriazolylpurine nucleoside 2b in MeOH, EtOH and PrOH used as solvents and nucleophiles in the presence of NaH

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• 14 resulted in the formation of alcohol 22, which was then reacted with nucleoside analogs via a Mitsunobu reaction to generate the racemic difluorinated carbocyclic homonucleoside analogs 23 and 24 in good yields. (Triphenylphosphonio)difluoroacetate (PDFA, Ph3P+CF2CO2−) as a difluorocarbene source

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• . Keywords: Arbuzov reaction; 2,6-bistriazolylpurines; nucleophilic aromatic substitution; purinylphosphonates; Introduction Acyclic nucleoside phosphonates (ANPs) are an important compound class due to their biological activity profile [1][2][3][4][5][6]. Compounds bearing a phosphonate moiety in their N9

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• biological applications. Review Nucleoside triphosphates detection Nucleoside triphosphates play crucial roles in several biological processes including energy transduction, cellular respiration, enzyme catalysis, and signaling [35][36][37][38]. They are the most targeted anionic species because of their

• ubiquitous presence in biological systems. Schmuck and co-workers reported a tweezer type peptide-based probe 1 for fluorescence detection of nucleoside triphosphates in aqueous media (Figure 2) [39]. The probe 1 consists of an environment-sensitive amino-naphthalimide fluorophore having two symmetric

• , UMP, TBAP, MMP or other anions (SO42−, NO3−, HCO3−, CH3COO−) does not show any enhancement of fluorescence enabling the probe as selective for nucleoside triphosphates. The probe 1 is not toxic and has been demonstrated by fluorescence imaging of ATP in HeLa cells (Figure 2A, inset). Nucleic acid

Incorporation of a metal-mediated base pair into an ATP aptamer – using silver(I) ions to modulate aptamer function

• Marius H. Heddinga and
• Jens Müller

Beilstein J. Org. Chem. 2020, 16, 2870–2879, doi:10.3762/bjoc.16.236

• versatility. The metal-mediated base pair chosen for this study is based on the artificial imidazole 2’-deoxyribonucleoside (Im). This nucleoside is well known to form highly stabilizing Ag(I)-mediated Im–Ag(I)–Im base pairs (Figure 1) [30][31][32][33] and has already been proposed for a use in various

• phosphoramidite-protected imidazole nucleoside as required for automated DNA solid-phase synthesis was synthesized as previously reported [30]. The oligonucleotides were synthesized on a DNA/RNA synthesizer H-8 (K&A Laborgeräte) using standard protocols for automated solid-phase synthesis (coupling time: 1000 s

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

• being preferentially formed. Optimization of the protection scheme lead to a new and economic route to the desired C8-alkynylated building block and its incorporation in RNA. Keywords: nucleoside chemistry; protecting groups; RNA synthesis; Sonogashira reaction; Introduction Oligoribonucleotides

• for 5’- or 3’-terminal attachment of a desired functionality, nucleoside derivatives that, upon site-specific incorporation at a pre-determined position of RNA, can be used for post-synthetic conjugation, are required. A number of chemistries are available to specifically attach a molecular entity to

• halide to iodine, taking into account that direct iodination of purines has been claimed being troublesome [26], although not impossible [27]. For C8-iodination of adenosine, first the hydroxy groups at the sugar moiety were protected with tert-butyldimethylsilyl (TBDMS) groups. The silylated nucleoside

Asymmetric Mannich reactions of (S)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimines with yne nucleophiles

• Ziyi Li,
• Li Wang,
• Yunqi Huang,
• Haibo Mei,
• Hiroyuki Konno,
• Hiroki Moriwaki,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2020, 16, 2671–2678, doi:10.3762/bjoc.16.217

• contains the trifluoromethylpropargylamine moiety and has been developed as the inhibitor against non-nucleoside reverse transcriptase for the treatment of human immunodeficiency virus [27] (Figure 1). Thus, the development of synthetic methods for the preparation of these compounds, featuring

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

• ; purine nucleoside phosphorylases; recombinant E. coli uridine; thymidine; Introduction Diverse variants of enzymatic syntheses of nucleosides using nucleoside phosphorylases as biocatalysts have been repeatedly described in original studies and discussed in a number of recent reviews (see, e.g., [1][2

• ][3][4][5][6][7][8][9][10][11][12][13][14][15]). In the late forties and early fifties of the last century, α-ᴅ-pentofuranose-1-phosphates (PF-1Pis) were isolated from the phosphorolysis of natural nucleosides catalyzed by nucleoside phosphorylases and their structures and enzymatic reactions with

• heterocyclic bases were studied in detail [16][17][18][19][20]. The transglycosylation reaction, that is the transfer of a carbohydrate fragment from a nucleoside donor to another heterocyclic base acceptor, was discovered by Kalckar in 1945 [16] (for reviews of pioneering works, see [17][18]). In a brief