Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• (CCD), aldehyde dehydrogenase (ALDH), uridine diphosphate glucosyltransferase (UGT). Structure of crocin and crocetin derivatives. A, SG, G, GB, and GT represent the common substituents of the crocin skeleton shown in Figure 1. Heterologous production of crocetin (1) and crocins. Acknowledgments We

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

• radical acceptor moieties. Therefore, we investigated the origin of this selectivity under electrochemical conditions. Results and Discussion Anodic oxidation of uridine derivative 1 was performed in a CH2Cl2/Bu4NPF6 (0.1 M) electrolyte system using a carbon felt (CF) anode and a Pt cathode in the

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

• linear cascade to produce the desired NTP. Figure 3b shows the reaction sequence from 5-fluorouridine-5’-monophosphate to the triphosphate in an enzymatic synthesis of an unnatural uridine nucleotide [42]. In these type of setup, the yield of the overall reaction is strongly determined by the position of

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

• ][40][41]. The structures of some of the uridine derivatives are shown in Table 1. In general, the attachment of amine-functionalized groups on the pyrimidine C-5 position positively affects both the thermal stability and the nuclease resistance of the resulting amine-modified ONs. A tris-aminated

• at the C-5 position of a 2’-OMe-uridine monomer, positioning the group in the major groove of the formed duplex, had a significant stabilizing effect on RNA binding (Table 2A, 18) [62]. Another method for introducing spermine at the N4 position involved the reaction of spermine and 4-N-p

• research. This has been explored utilizing the reactivity between primary amines and the aldehyde moiety of a 2’-O-(2-oxoethyl)uridine nucleotide, incorporated centrally in an 11-mer TFO, to form a Schiff base (monomers 41–45) [80]. All aminoalkylated moieties improved the triplex stability. Notably, a

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• complementarity as well. An elegant solution to this problem has been to use 2,6-diaminopurine (D) instead of adenosine and 2-thiouridine (s2U) instead of uridine as modified nucleobases in PNAs designed for double duplex invasion [129][130]. D and s2U form more stable Watson–Crick base pairs with T and A

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

• . The convergent synthesis of the double-headed nucleosides was achieved from uridine, which was first converted to the 3′,5′-(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl)-protected (TIPDS) ketonucleoside 1 following a standard procedure [40]. The subsequent Corey–Chaykovsky epoxidation [41] of 2

• ]. Nielsen and co-workers [42] additionally synthesized 2′-(N-benzoylcytosin-1-yl)methylarabinofuranosyl-N-benzoylcytosine (7) from uridine using a similar methodology. Thus, the nucleophilic epoxide ring opening in spironucleoside 2 with uracil in DMF in a N1-regioselective manner afforded the TIPDS

• ]. Nielsen and co-workers [43] synthesized 2′-(4-(thymin-1-ylmethyl)-1,2,3-triazole-1-yl)- and 2′-(4-(N6-benzoyladenine-9-ylmethyl)-1,2,3-triazole-1-yl)-substituted double-headed nucleosides of 2′-deoxy-5′-O-(4,4′-dimethoxytrityl)uridine (14 and 15) from the nucleoside azide 12 which in turn was obtained by

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

• ) (TIPDS) protected uridine, protection of N3 was needed in order to prevent methylation at this position (Scheme 4). The N3-benzoylated derivative could then be treated with methyl iodide in the presence of silver oxide in order to methylate the 2'-OH. A similar strategy was employed to synthesize 3',5'-O

• 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

• ribonucleotide had a high resemblance to the unmodified uridine, allowing it to be used as a probe for RNA structure determination through 19F NMR [211]. This modification led to RNA which was stable and predominantly in the C3'-endo (north) conformation [211], similar to the 2',4'-diF-RNA previously reported by

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

• Yongdong Su,
• Maitsetseg Bayarjargal,
• Tracy K. Hale and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2021, 17, 749–761, doi:10.3762/bjoc.17.65

• -phase DNA or RNA synthesis, the introduction of SaRNA monomers into an RNA backbone involved a 14-step preparation of the phosphoramidite for the SaRNA-TT dinucleotide. Similarly, the incorporation of BCNS groups on a DNA backbone requires the synthesis of thymidine and 2’-OMe-uridine phosphoramidites

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• the aforementioned issues, Virta and co-workers have explored the application of trifluoromethyl analogues of guanosine, cytidine and uridine based in 2’-O-[(4-trifluoromethyltriazol-1-yl)methyl] reporter groups as 19F NMR probes for the detection of RNA secondary structures (Figure 14). As shown by

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

• 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

• synthesized a number of pyrimidine and purine derivatives carrying amino linkers of different length and flexibility [13][20]. Linker-modified uridine derivatives, upon conversion into phosphoramidite building blocks, were incorporated in RNA and used for a systematic study of distance determination of

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

• found that phosphorolysis of uridine, thymidine, and Ara-U in the presence of Dowex® 1X8 (phosphate; Dowex-nPi) proceeded smoothly in the presence of magnesium cations in water at 20–50 °C for 54–96 h giving rise to quantitative formation of the corresponding pyrimidine bases and PF-1Pis. The resulting

• ; 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

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• enzymes require an activated sugar donor uridine diphosphate (UDP)-Galf, which is synthesized from UDP-galactopyranose (UDP-Galp) by the enzyme UDP-Galp mutase [9] (Supporting Information File 1, Figure S1). The recently published GlfT2 X-ray structure with a UDP donor part [10] was used in the reaction

• hydroxy group with the aspartate D256 has also been seen. The SO2 unit attached to alkyl/aryl substituents have been found in two main binding modes. In one binding mode the alkyl/aryl part is bound towards the uridine binding pocket of the UDP-Galf. The second binding mode was found in the place where

• structures do not include the uridine mimicking part which can increase the binding affinity significantly. Attaching of this part is a topic of further synthesis and second-generation compound library preparation. We believe that our further efforts, both in synthetic and computational fields, will point to

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• and the glycosyl transfer have not been fully explored yet. Previously, Kline and co-workers reported on the synthesis of acetylated 4-azido-arabinose phosphate and uridine diphosphate (UDP) derivatives. In addition, a 4-aminophosphoamidate UDP derivative was also obtained [8]. Whereas these compounds

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

• functionalization by way of propargyl dicobalt cation chemistry. Nucleoside modifications are considerably challenging due to the presence of reactive functional groups. Since numerous uridine C-5 modifications play an important role in biochemistry, we considered exploration of pertinent methods development

• , triethylamine, in DMF, and at room temperature – to avoid cycloisomerization to furopyrimidines (Scheme 1). The modified pyrimidine nucleoside scaffolds, propargyl acetate-substituted 2'-deoxyuridine (R = Ac, 2) and propargyl methyl ether-substituted uridine (R = Me, 3), were obtained in 87% and 61% yield

• ions’ masses. The solutions of uridine complexes 4 and 5 in dichloromethane were subjected to Nicholas reactions with a variety of diverse nucleophiles in the presence of BF3·OEt2. Representatives of the major classes of C-based nucleophiles in Nicholas reaction chemistry were selected, including

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• were obtained in moderate yields [104]. Aiming at an improved procedure to synthesize nucleosides with glycosylation of the nucleobase, De Napoli et al. used the Bu3P-ADDP system to connect inosine and uridine derivatives with D-ribofurano and D-glucopyrano moieties [105]. Hocek’s group in 2015

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• antibiotics, among others, such 'high-carbon' nucleosides are uridine-derived amino acid structures ('glycyluridine', GlyU) [78][79][80], which are aminoribosylated at the 5'-hydroxy group. As part of our ongoing research program on muraymycin nucleoside antibiotics (e.g., muraymycin A1 (44)) and their

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• presence of excess nucleoside (1.1 equiv), the corresponding 5′-trityl ethers of uridine, adenosine or thymidine were isolated in yields up to 86%. Reactions of guanosine or cytidine under these conditions gave rise to mixtures of products from which the corresponding tritylated products could not be

• isolated. Subsequently, Patil and Kartha described the gram-scale preparation of 5′-tritylated uridine derivatives in a planetary ball mill (using a steel vessel and balls) in the absence of TBAB [40]. Following extended grinding (600 rpm for 15 hours) of the nucleoside in the presence of excess DABCO and

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• fission of the intermediate to a 2´,3´-cyclic phosphate, leading to pH-independent cleavage, is much slower (Scheme 1). The rate of this reaction (black line in Figure 6) is only 2% of the interconversion rate of 2´,5´- and 3´,5´-diesters [44]. Studies with various uridine 3´-alkylphosphates have, however

• ). Combined QM/MM simulations have lent support for this interpretation [47]. With triester analogs, such as uridine 3´-diethyl phosphate, the latter intramolecular proton transfer is not possible and the ratio kcl/kis is much smaller than with the diester analog, around 10−5 [50]. Since the barrier for the

• phosphorane that decomposes to 2´,3´-cyclic phosphate by departure of the 5´-linked nucleoside as an alkoxide ion (Scheme 3). The stability of the dianionic phosphorane has been studied by experimental and computational methods. As mentioned above, the βlg value of the reaction of uridine 3´-alkyl phosphates

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

• exhibits anti-influenza activity. C-nucleoside variants of favipiravir riboside and their base pairing with uridine and cytosine. B. Synthesis of C-nucleoside variants of favirpiravir starting from D-ribonolactone. Alternative method for synthesis of 2'-substituted C-nucleosides [75]. A. Synthesis of C2

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• varied from 53 h to 63 h for ribonucleotides [34]. Our results were thus comparable to the ones obtained by Ruzicka and Frey who studied the hydrolysis of 5'-phosphorimidazolates of uridine at different pH values [41] and found a half-life toward hydrolysis of about 60 h in the absence of Mg2+ and at

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• siRNA–mRNA hybrid, disturbing the cleavage of mRNA by the RISC. Subsequently, Deiters used the same approach with photo 6-nitropiperonyloxymethyl (NPOM)-photocaged siRNAs synthesized from phosphoramidites of the caged uridine and guanosine ribonucleotides (Scheme 20B) [83]. As previously demonstrated

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• trypanosomatid cap4 structure, characterized by 2′-O-methylation of the first four nucleotides and additional methylation at the first adenosine and the fourth uridine, was reported in 2004 by the group of Darzynkiewicz. The preparation was achieved by reacting an imidazole activated m7GDP with the 5

Effect of uridine protecting groups on the diastereoselectivity of uridine-derived aldehyde 5’-alkynylation

• Raja Ben Othman,
• Mickaël J. Fer,
• Laurent Le Corre,
• Sandrine Calvet-Vitale and
• Christine Gravier-Pelletier

Beilstein J. Org. Chem. 2017, 13, 1533–1541, doi:10.3762/bjoc.13.153

• -Paris), 45 rue des Saints Pères, 75270 Paris 06, France 10.3762/bjoc.13.153 Abstract The 5’-alkynylation of uridine-derived aldehydes is described. The addition of alkynyl Grignard reagents on the carbonyl group is significantly influenced by the 2’,3’-di-O-protecting groups (R1): O-alkyl groups led to

• ; nucleoside; protecting groups; uridine; Introduction Nucleoside and nucleotide derivatives or analogues are biologically active compounds of major interest [1][2]. Their widespread applications span from therapeutic agents, such as antibacterial [3][4][5], antiviral [6] or antitumor [7][8] drugs, to

• organometallic reagents onto nucleoside aldehyde (Table 1), we decided to investigate the influence of the protecting groups of the uridine aldehyde on the stereochemical outcome of the nucleophilic addition of a Grignard reagent and we wish to report herein the results of our study. Results and Discussion We

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

• saccharides. The interest in hexofuranoses is based on the arabinogalactan-rich membrane of Mycobacterium tuberculosis and other harmful microorganisms which consists of primarily Araf and Galf subunits [44]. One key step in the biosynthesis of these hexofuranoses is the isomerization of uridine 5′-diphospho

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

• direct approach for the synthesis of kipukasin A was the regioselective modification of commercially available uridine (Figure 2, path a). After carefully assessment, we realized that it would require several steps of protection and deprotection. Especially under alkaline conditions, 2’,3