The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• neighbouring group participation for the formation of the acetoxonium ion intermediate was more favourable in the locked systems like o-substituted benzoyl groups instead of aliphatic protections. Many protecting groups have been developed for the protection of the amine functionality of nucleosides like 2

• -(benzoyloxymethyl)benzoyl [89] and 2-[(tert-butyldiphenylsilyloxy)methyl]benzoyl [90] among others. Sekine and co-workers developed the 2-(azidomethyl)benzoyl (AZMB) group for protecting the hydroxy groups and the exo-amino functionality of the nucleosides [91]. Despite their disarming nature, Iadonisi et al

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• bioinformatic analysis. Their updated PRISM 4 pipeline outperformed antiSMASH5 and was able to predict the chemical structures of a wide variety of secondary metabolites [90]. Notably, the repertoire of PRISM 4 spans beyond NRPs and PKs and includes alkaloids, terpenoids, aminoglycosides, nucleosides, etc

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• nucleophilicity. In their second work about this topic, Prasad et al. synthesized 5-(3”-alkyl/arylamino-1”-azaindolizin-2”-yl)-2’-deoxyuridines 31 as new base-modified fluorescent nucleosides with high Stokes’ shift, potentially useful for investigating nucleic acid structure and functions. The authors

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• synthesized and tested for antimicrobial activity. However, no clear trend was found between the ester length and bioactivity. In addition to the paraben derivatives, three known nucleosides, 4´,5´-didehydro-5´-deoxyinosine (18), 2´-O-methyladenosine (19), and 5´-methylthioinosine (20) were also identified

• structures of sulfated polysaccharides κ-, ι-, and λ-carrageenans. Chemical structures of 4HBA (1) and parabens (2–14) isolated from Microbulbifer strains, and synthetic analogus (15–17). Chemical structures of nucleosides 18–20 isolated from Microbulbifer strains. Chemical structures of alkaloids 21–24

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• scaffold, compounds Va–c (Figure 1B), in which the N3 atom present in the nucleobase of IV is replaced by CH2. We assumed that this change should not significantly affect the inhibitory potential but rather increase the stability of the target nucleosides in water and allow chemical incorporation into

• ssDNA. Results and Discussion Synthesis of nucleosides It is more straightforward to start the synthesis of a modified nucleoside from the assembly of a nucleobase that can be coupled to the sugar afterwards using the Hilbert–Johnson reaction or a silyl variation of it as described in the literature [65

• phosphinic acid 7 was further protected with benzyl alcohol by a procedure adopted from reference [67] using TBTU and Et3N in refluxing dichloroethane. Compound 8 was obtained in 65% yield after silica gel column chromatography. To synthesise a nucleobase for nucleosides Va and Vb, we first obtained

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• reports of Karban et al. (Scheme 2) [19]. We envisaged that these hexose-derived building blocks with a 2,5-anhydro bond such as 5 could be useful materials for the construction of C-nucleosides such as formycin A (Figure 1) [22][23][24]. The preparation of C-glycosides usually involves the creation of

Additive-controlled chemoselective inter-/intramolecular hydroamination via electrochemical PCET process

• Kazuhiro Okamoto,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2024, 20, 264–271, doi:10.3762/bjoc.20.27

• avoided [9]. The initial aim of this study was the electrochemical generation of an amidyl radical as a HAT source for the synthesis of 1’-C functionalized nucleosides via the generation of an anomeric radical species from uridine derivative 1 (Figure 1, bottom) [10]. Although the HAT reaction failed

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

• nucleosides thereof [10][11][12], mostly associated with the inhibition of adenosine deaminase (ADA) [11] and as adenosine receptor antagonists [10]. Another important field of applications for deaza-modified nucleobases is their use in atom-specific mutagenesis experiments. For example, site specific 1-, 3

• -, and 7-deazapurine mutations of RNA have been fundamental to shed light on their structure, catalysis, and function [13][14][15]. However, difficulties in these fields arise from the lack of efficient synthetic protocols for various deaza-nucleosides and nucleobases. This is particularly true for the

• intermediates. Here, we present a new tactic for the syntheses of 1-deazaguanine and 1-deazahypoxanthine stimulated by a recently published route of our research group for the corresponding nucleosides [16][17], employing the same key reaction, namely the copper-catalyzed coupling of an aryl iodide with benzyl

Ferrocenoyl-adenines: substituent effects on regioselective acylation

• Mateja Toma,
• Gabrijel Zubčić,
• Jasmina Lapić,
• Senka Djaković,
• Davor Šakić and
• Valerije Vrček

Beilstein J. Org. Chem. 2022, 18, 1270–1277, doi:10.3762/bjoc.18.133

• the acylation of purines from a regioselective to a regiospecific mode. Keywords: DFT; ferrocene; nucleophilicity; purine; steric effect; Introduction Nucleosides in which the sugar part is replaced with an organometallic moiety have attracted remarkable interest [1][2][3]. One important class are

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

• chemoenzymatic method was found to be superior over the chemical method in respect of the number of synthetic steps and overall yield of the final product. Keywords: bicyclic AZT analogues; bridged homoarabinofuranosylpyrimidine nucleosides; chemical pathway; Lipozyme® TL IM; regioselective enzymatic

• 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

• azido-carbobicyclic nucleosides 2 and 3, where compound 2 showed activity similar to that of AZT while compound 3 was devoid of any type of activity (Figure 1). Nielsen et al. [22] synthesized the conformationally restricted nucleoside 4, which was devoid of any anti-HIV activity. Further, Zhang et al

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

• accompanied by coupling nucleobases via N-glycosylation. However, over the last three decades, efforts were made for the synthesis of 1,3-oxathiolane nucleosides by selective N-glycosylation of carbohydrate precursors at C-1, and this approach has emerged as a strong alternative that allows simple

• modification. This review aims to provide a comprehensive overview on the reported methods in the literature to access 1,3-oxathiolane nucleosides. The first focus of this review is the construction of the 1,3-oxathiolane ring from different starting materials. The second focus involves the coupling of the 1,3

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

• first reacted with either of the three diaminoalcohol groups, before subsequent phosphitylation with the DMT-protected nucleosides [115]. After incorporation into ONs, conversion to monomers 78–81 was accomplished as shown in Table 8. Although monomer 78 showed good yield in both phosphoramidite

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• ], electron-rich alkenes (entry 3) [65][66], alkyl sulfides (entry 4) [65][67], 1,3-dicarbonyl compounds [65][68], phosphonate esters (entry 5) [65], steroidal silyl enol ethers and enol acetates (entry 6) [65], pyrimidine bases and nucleosides (entry 7) [67][69], phenylalkynes (entry 8) [70], anthraquinones

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

• of deoxyribonucleic acids (DNA) or ribonucleic acids (RNA), which contain either a purine or pyrimidine nucleobase and a furanosyl moiety of pentose sugars, 2′-deoxyribose or ribose [1][2]. Nucleotides are constituted by addition of a phosphate group at the 5′-position of the nucleosides and these

• 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

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

• modifications reported by chemists along with the synthesis of 2'-deoxy-2'-fluoro-nucleosides (FRNA) [24]. The negatively charged phosphodiester linkages in the backbones of DNA and RNA are of fundamental importance for reactivity, stability, conformation and hydration [25][26]. The sugar moieties in DNA and

• )-modified oligonucleotides was first described in 1991 by the Caruthers group [84]. Typically, each 2'-deoxynucleoside 3'-phosphorothioamidite is prepared by phosphitylating the protected nucleosides with tris(pyrrolidino)phosphine under tetrazole catalysis, followed by immediate treatment with

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

• ring at the C6 position of purine to act as leaving group. Keywords: 2,6-bistriazolyl purines; nucleophilic aromatic substitution; purine nucleosides; triazoles; Introduction Modified purine derivatives are an important class of compounds which possess a wide spectrum of biological activities [1][2

• compounds 5a–d. Synthetic pathways for the synthesis of 6-substituted 2-triazolylpurine derivatives IV. Synthesis of 2,6-bistriazolylpurine derivatives 2a–c. Synthesis of 6-alkyloxy-2-triazolylpurine derivatives 3a–f. Synthesis of 6-alkyloxy-2-triazolylpurine nucleosides 3g–j. 2,6-Bistriazolylpurine

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

• targets of biological interest was provided by Csuk and Eversmann [32] who performed the synthesis of difluorinated nucleosides (Scheme 11). The difluorocyclopropane derivative 14 was prepared using sodium chlorodifluoroacetate (12) as a source of the carbene (Scheme 11). The subsequent deacetylation of

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

• activity against Mycobacterium tuberculosis and also as agonists and antagonists of adenosine receptors [18]. In 2013, we developed an efficient approach for the synthesis of ribo- and arabino-2,6-bistriazolylpurine nucleosides and showed that the triazolyl ring in the C6 position of purine acts as a good

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

• for unnatural nucleosides). All natural nucleosides (A, T, G, and C), the fluorescein phosphoramidite as well as the DABCYL-CPGs were obtained from Glen Research. The oligonucleotides were deprotected and cleaved from the support by incubation in AMA solution (1:1, 40% methylamine and aqueous ammonia

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

• , functionalized phosphoramidite building blocks of all four nucleosides are highly desired. The number of commercially available RNA phosphoramidites that carry a suitable functionality for post-synthetic attachment of dyes, reporter groups or other conjugates is still rather limited. In particular, monomer

• building blocks of the purine nucleosides with functionalities suitable for post-synthetic conjugation at the nucleobase are basically missing, and also in the pyrimidine series, the few existing derivatives of uridine do not offer much variety. Motivated by this lack of functional building blocks, we have

• 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

• substrates of the phosphorolysis of uridine, thymidine, and 1-(β-ᴅ-arabinofuranosyl)uracil (Ara-U) catalyzed by recombinant E. coli uridine (UP) and thymidine (TP) phosphorylases. α-ᴅ-Pentofuranose-1-phosphates (PF-1Pis) obtained by phosphorolysis were used in the enzymatic synthesis of nucleosides. It was

• PF-1Pis can be used in three routes: (1) preparation of barium salts of PF-1Pis, (2) synthesis of nucleosides by reacting the crude PF-1Pi with an heterocyclic base, and (3) synthesis of nucleosides by reacting the ionically bound PF-1Pi to the resin with an heterocyclic base. These three approaches

• were tested in the synthesis of nelarabine, kinetin riboside, and cladribine with good to excellent yields (52–93%). Keywords: anion exchange resins; N6-benzyladenosine; cladribine; enzymatic glycosylation; kinetin riboside; nelarabine; α-ᴅ-pentofuranose-1-phosphates; phosphorolysis of nucleosides

The B & B approach: Ball-milling conjugation of dextran with phenylboronic acid (PBA)-functionalized BODIPY

• Patrizia Andreozzi,
• Lorenza Tamberi,
• Elisamaria Tasca,
• Gina Elena Giacomazzo,
• Marta Martinez,
• Mirko Severi,
• Marco Marradi,
• Stefano Cicchi,
• Sergio Moya,
• Giacomo Biagiotti and
• Barbara Richichi

Beilstein J. Org. Chem. 2020, 16, 2272–2281, doi:10.3762/bjoc.16.188

• range of biomolecules: amino acids [8], peptides [9], glycosides [10], nucleosides/nucleotides [11], and lipids [12]. Also, protein-based nano-bio-conjugates [13] have been prepared by ball milling, retaining the native properties of the proteins after mechanochemical synthesis. Boronic acids and their

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• N-heterocyclic compounds such as phenanthridine, carbazole, and dibenzo[b,d]azepine. Simultaneously, Guo’s group published the arylation of nucleosides bearing a purine moiety. The transformation was regioselective and tolerated various substituents at the N9 position of the purine, including sugar

• features when working with biological systems. Thus, a variety of functionalized purines nucleosides that are potentially of great importance in medicinal chemistry were obtained in good yields. In contrast to C(sp2)–H bonds, C(sp3)–H bond activation is much more challenging. Inspired by the potential of

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• of anal gland secretions of the stoat [1] and the ferret [2]. Some pharmaceutical and biological thietane-containing compounds include thiaanalogue thietanose nucleosides 1 and 2 [3][4], and the spiroannulated glyco-thietane nucleoside 3 [5] of the antiviral (anti-HIV and HSV) drug oxetanocin A, the

• 1966 [32]. They treated 3,5-dichloropentan-2-ol (9) with K2S to produce 1-(thietan-2-yl)ethan-1-ol (10) in 65% yield (Scheme 1). In 2007, Nishizono and co-workers used 2,2-bis(bromomethyl)propane-1,3-diol (11) as starting material to prepare thietanose nucleosides 2 and 14. They first carried out a

• double displacement with sodium sulfide to obtain thietane-3,3-diyldimethanol (13), which was further converted into two different thietanose nucleosides 2 and 14 [33] (Scheme 2). In the synthesis of sesquiterpene thioalkaloids, the method also was utilized. A double-aldol condensation of methyl