N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• of β-16a with 3-acetoxy-5-chloroindole. Anomerically pure indirubin-N-glucoside β-18a, indirubin-N-riboside β-19a, indirubin-N-galactoside β-20a, and indirubin-N-mannoside β-21a were prepared in good yields starting from the corresponding sugars and anilines [12][13]. In case of the indoxyl moiety

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

• of the University of Auckland, Level 2, 3A Symonds Street, Auckland 1142, New Zealand 10.3762/bjoc.20.96 Abstract Nucleoside and polynucleotide cytidine deaminases (CDAs), such as CDA and APOBEC3, share a similar mechanism of cytosine to uracil conversion. In 1984, phosphapyrimidine riboside was

• inhibition of APOBEC3A was observed for modified DNAs. Although this shows that the negative charge is poorly accommodated in the active site of CDA and APOBEC3, the synthetic route reported here provides opportunities for the synthesis of other derivatives of phosphapyrimidine riboside for potential

• been synthesised in the past and evaluated as inhibitors targeting the active site of CDA. THU (Ia) [45][48], zebularine (Z, IIa) [47][49][50] and 5-fluorozebularine (FZ, IIb) [47][51] as well as diazepinone riboside (IIIa) [42][43][44][52] were among the most potent compounds (Figure 1B). THU (Ia

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

• 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

• amounts of inosine and phosphate as starting material it was found that only 10 per cent of the riboside undergoes phosphorolysis at pH 6.5” [16]. Presently, the observation made by Kalckar is one of the hot issues from a viewpoint of the development of efficient enzymatic synthesis of nucleosides

• nucleoside. The possibility of using the filtrate obtained in the 1st way as a source of PF-1Pis was tested by the enzymatic synthesis of nelarabinе and kinetin riboside (KR). The choice of these two nucleosides was primarily determined by their biological activities: nelarabine was approved by the Food and

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• Mikhail V. Makarov Marie E. Migaud Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Ave., Mobile, AL 36604, USA 10.3762/bjoc.15.36 Abstract The β-anomeric form of nicotinamide riboside (NR+) is a precursor for nicotinamide adenine dinucleotide (NAD+), a redox cofactor

• modifications which have been undertaken on the nicotinoyl riboside scaffold. Keywords: anomers; glycosylation; isotopologues; isotopomeres; nicotinamide riboside; Review 1. Introduction 1-(β-D-Ribofuranosyl)nicotinamide (also referred to as nicotinamide riboside, NR+) is one of the multiple precursors of

• . 2. Synthesis of β-nicotinamide riboside Most synthetic routes to nicotinamide riboside salt forms (NR+X−) may be subdivided into two main categories (Figure 2). One is via a reaction between nicotinamide (Nam) or its analogues or derivatives A and a peracylated (halo)-D-ribofuranose B resulting in

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

• using LAG (Scheme 9) [45]. Yields were slightly enhanced following presilylation of the bases in solution prior to ball milling and under these conditions, the corresponding protected 6-chloropurine riboside could also be accessed. Multiple products were formed from N2-iso-butyrylguanine and

• mills [46][47]. Reaction scales up to 40 g were described and the conditions developed enabled exclusive formation of the β-anomer of nicotinamide riboside (NR) in the absence of toxic bromide salts. Preparation and reactions of nucleotides and their analogues Phosphorylation of NR on gram-scales using

• in a MBM. Thiolate displacement reactions of nucleoside derivatives in a MBM. Selenocyanate displacement reactions of nucleoside derivatives in a MBM. Nucleobase glycosidation reactions and subsequent deacetylation performed in a MBM. Regioselective phosphorylation of nicotinamide riboside in a MBM

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

• give the desired cyclopentane ring (23) [73]. The biological data of these compounds has yet to be reported. Wang et al. synthesized a series of pyridine and pyrimidine C-nucleosides (24–26) that mimic the riboside of favipiravir in their effort to develop novel anti-influenza compounds (Figure 10A

• exhibited potent activity against the H1N1 influenza strain (A/WSN/33) in cell based assays [74]. The pyrimidine compound 26 was synthesized using an identical approach and is not shown here. The activity of 24 and 25 as nucleosides was comparable to favipiravir and its riboside. Furthermore, they found

• for structure–activity relationship [71][72]. Synthesis of 1',2'-cyclopentyl C-nucleoside [73]. Functional groups at C1' and C2' were installed and employed for ring cyclization. Anti-influenza C-nucleosides mimicking favipiravir riboside [74]. A. Structure of favipiravir and its riboside, which

Synthesis of ribavirin 2’-Me-C-nucleoside analogues

• Fanny Cosson,
• Aline Faroux,
• Jean-Pierre Baltaze,
• Jonathan Farjon,
• Régis Guillot,
• Jacques Uziel and
• Nadège Lubin-Germain

Beilstein J. Org. Chem. 2017, 13, 755–761, doi:10.3762/bjoc.13.74

• the Huisgen cycloaddition reaction onto the C-alkynyl riboside intermediately obtained [14]. Herein we describe the synthesis of two new carbonated analogues 2 and 3 of RBV modified at the 2’-position (Figure 1). In fact, a quaternization in 2’-position of various nucleosides led to a higher efficacy

• commercially available 2-C-methyl-1,2,3,5-tetra-O-benzoyl-β-D-ribofuranose (4) as shown in Scheme 1. Debenzoylation of 4 followed by selective protection led to derivative 5, which was submitted to the indium-mediated alkynylation reaction affording the alkynyl riboside 6 with the same β-anomeric selectivity

• differentiate the 2’ position. After the indium-mediated alkynylation, the obtained alkynyl riboside 8 was submitted to a Huisgen cycloaddition reaction with benzyl azide, under the same conditions as in the previous case, affording the mixture of regioisomeric triazoles 9a and 9b in a 37:63 ratio [14] (Scheme

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

• publications are available on the enzymatic synthesis of these nucleosides. W. H. Prusoff reported on the first efficient transformation of 6-azathymine into its 2'-deoxy-D-riboside in phosphate buffer (50 mM, pH 8.0; 37 °C) in the presence of thymidine as a pentofuranose donor and washed cells or cell-free

• preparation of trans-N-deoxyribosylase from Lactobacillus helveticus NCIB 6557 [30] had been described [31]. As for an enzymatic synthesis of thioxopyrimidine nucleosides, Kalckar [32] as well as Friedkin and co-workers [33][34] disclosed the formation of 2-thiouracil riboside and 2'-deoxyriboside using 2

Facile synthesis of a 3-deazaadenosine phosphoramidite for RNA solid-phase synthesis

• Elisabeth Mairhofer,
• Elisabeth Fuchs and
• Ronald Micura

Beilstein J. Org. Chem. 2016, 12, 2556–2562, doi:10.3762/bjoc.12.250

• ], started from inosine leading to c3A after 8 steps via a 5-amino-4-imidazolecarboxamide (AICA) riboside derivative with 8% overall yield. Another 4 steps followed to achieve a properly protected building block for RNA solid-phase synthesis [16]. With a total of 12 steps, the approach is not very attractive

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

• analogs of natural products nebularine and 6-methylpurine riboside were constructed via our convergent synthetic strategy. Synthesized nucleosides were tested against HT116 (colon cancer) and 143B (osteosarcoma cancer) tumor cell lines. We have demonstrated 3’-fluorine purine nucleoside analogues display

• ’-fluoro-adenosine 1 in 93% yield. We targeted 9-(3-deoxy-3-fluoro-β-D-ribofuranosyl)purine (1) in particular because it is the 3’-fluorine analogue of nebularine, a naturally occurring antibacterial and antineoplastic agent [42][43]. 3’-Fluoro-6-methylpurine riboside 4, a 6-β-D-MPR mimic 6-Methylpurine-β

• -D-riboside (6-β-D-MPR) is an isolated antibiotic agent that possesses potent antifungal, antiviral, and antitumor activities [44]. In order to explore the effect of fluorine on the biological activity of this pharmacophore, we synthesized 6-methylpurine-3’-deoxy-3’-fluoro-β-D-riboside (4) (Scheme 2

Synthesis of D-fructose-derived spirocyclic 2-substituted-2-oxazoline ribosides

• Madhuri Vangala and
• Ganesh P. Shinde

Beilstein J. Org. Chem. 2015, 11, 2289–2296, doi:10.3762/bjoc.11.249

• spirooxazolines are stable and were obtained in good yield with high stereoselectivity due to the conformational rigidity imparted by the 3,4-isopropylidene group. Keywords: fructose; oxazoline; riboside; Ritter reaction; spiro; Introduction 2-Oxazolines represent a unique class of 5-membered heterocyclic

• as a single diastereomer in good yield. In the absence of the nucleophile, the oxacarbenium-ion intermediate of protected D-psicofuranose derivatives underwent spiroketalization to give di-D-fructose dianhydrides. Given the established, pharmacological applications of riboside derivatives, these

• stable, conformationally constrained riboside spirooxazolines open up the possible application in the development of new drug molecules. In addition, these highly functionalized glycooxazolines can be used to make covalently cross-linked polymers for application in nanomedicine and material science. Some

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

• ',3'-bis-O-(tert-butyldimethylsilyl)-1-[4-(N'-biotinyl-3,6-dioxaoctane-1,8-diamine)pyrimidine-2(1H)-onyl]-β-D-riboside (12). I: 2.6 equiv ZnBr2, DCM, 1 d, rt, Ar, 82%; II: 1.1 equiv EDAC·HCl, 1.1 equiv biotin, DMF, 0 °C → rt, overnight, 65%; III: THF/TFA/H2O (4:1:1, v/v/v), 0 °C, 5 h, 94%. Formation

Investigation of acetyl migrations in furanosides

• O. P. Chevallier and
• M. E. Migaud

Beilstein J. Org. Chem. 2006, 2, No. 14, doi:10.1186/1860-5397-2-14

• O. P. Chevallier M. E. Migaud School of Chemistry and Chemical Engineering, Queen's University, David Keir Building, Stranmillis Road, Belfast, BT9 5AG, Northern Ireland, UK 10.1186/1860-5397-2-14 Abstract Standard reaction conditions for the desilylation of acetylated furanoside (riboside

• characterisations have been limited.[9][10][11] Whilst attempting the synthesis of 1-O-acetyl, 2,3-isopropylidene riboside 1a from the 5-O-silylated precursor 1 (Scheme 1) using mild desilylating conditions, three compounds were isolated, evidently products of acyl migration processes. In order to synthesise

• experimental data). Riboside 1 was synthesised from ribose in 47% overall yield via a chemoselective silylation of the C-5 primary hydroxyl group of 2,3-O-isopropylidene ribose (Scheme 2). The acetylated xyloside 2 and riboside 3 were both synthesised from xylose in 46% and 45% overall yield, respectively. The