cas 7473-45-2, Methyl beta-D-ribofuranoside

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Highly stereoselective glycosidation of ribose solubilized in apolar organic media via host-guest complexation
Ribose complexed with resorcinol-dodecanal cyclotetramer via hydrogen bonding in CCl4 undergoes highly stereoselective glycosidation with methanol to give methyl β-ribofuranoside under mild and neutral conditions.
Tanaka, Yasutaka,Khare, Chinmai,Yonezawa, Masaki,Aoyama, Yasuhiro
p. 6193 - 6196
(1990)
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Furanosic forms of sugars: Conformational equilibrium of methyl β-d-ribofuranoside
The investigation of an isolated ribofuranose unit in the gas phase reveals the intrinsic conformational landscape of the biologically active sugar form. We report the rotational spectra of two conformers of methyl β-d-ribofuranoside in a supersonic jet expansion. Both conformers adopt a near twisted (3T2) ring conformation with the methoxy and hydroxymethyl substituents involved in various intramolecular hydrogen bonds.
écija, Patricia,Uriarte, Iciar,Spada, Lorenzo,Davis, Benjamin G.,Caminati, Walther,Basterretxea, Francisco J.,Lesarri, Alberto,Cocinero, Emilio J.
p. 6241 - 6244
(2016)
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Stereoselective Synthesis of Ribofuranoid exo-Glycals by One-Pot Julia Olefination Using Ribofuranosyl Sulfones
One-pot Julia olefination using ribofuranosyl sulfones is described. The α-anomers of the ribofuranosyl sulfones were synthesized with complete α-selectivity via the glycosylation of heteroarylthiols using ribofuranosyl iodides as glycosyl donors and the subsequent oxidation of the resulting heteroaryl 1-thioribofuranosides with magnesium monoperphthalate (MMPP). The Julia olefination of the α-ribofuranosyl sulfones with aldehydes proceeded smoothly in one pot to afford the thermodynamically less stable (E)-exo-glycals with modest-to-excellent stereoselectivity (up to E/Z = 94:6) under the optimized conditions. The E selectivity was especially high for aromatic aldehydes. In contrast, the (Z)-exo-glycal was obtained as the main product with low stereoselectivity when the corresponding β-ribofuranosyl sulfone was used (E/Z = 41:59). The remarkable impact of the anomeric configuration of the ribofuranosyl sulfones on the stereoselectivity of the Julia olefination has been rationalized using density functional theory (DFT) calculations. The protected ribose moiety of the resulting exo-glycals induced completely α-selective cyclopropanation on the exocyclic carbon-carbon double bond via the Simmons-Smith-Furukawa reaction. The 2-cyanoethyl group was found to be useful for the protection of the exo-glycals, as it could be removed without affecting the exocyclic C=C bond.
Oka, Natsuhisa,Mori, Ayumi,Suzuki, Kanna,Ando, Kaori
p. 657 - 673
(2020/12/23)

MODIFIED OLIGOMERIC COMPOUNDS AND USES THEREOF
The present disclosure provides oligomeric compounds comprising a modified oligonucleotide having at least one stereo-non-standard nucleoside. An oligomeric compound comprising a modified oligonucleotide consisting of 12-30 linked nucleosides, wherein at least one nucleoside of the modified oligonucleotide is a stereo-non-standard nucleoside; and wherein the oligomeric compound is selected from among an RNAi compound, a modified CRISPR compound, and an artificial mRNA compound.
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Page/Page column 119-121

(2021/02/19)

Novel saccharide bio-based cyclic phosphorus/phosphonate as well as preparation method and application thereof
The invention discloses novel saccharide bio-based cyclic phosphorus/phosphonate as well as a preparation method and application thereof, and belongs to the field of compounds. The cyclic phosphorus/phosphonate is prepared by the following steps: reacting D-xylose with acetyl chloride to obtain an intermediate product, and then reacting with dichlorophosphate or phosphonic dichloride under the action of an acid-binding agent to obtain a target product. The preparation method is high in yield, simple in process, low in raw material cost and small in environmental pollution, and the prepared cyclic phosphorus/phosphonate flame retardant is outstanding in flame retardance and easy to industrialize.
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Paragraph 0039; 0041-0042

(2021/09/04)

BIOMARKER PANEL TARGETED TO DISEASES DUE TO MULTIFACTORIAL ONTOLOGY OF GLYCOCALYX DISRUPTION
The present disclosure provides biomarkers useful as companion diagnostics for detecting glycocalyx-based disease that is amenable to treatment using compounds designed for improving the condition of the glycocalyx and/or reducing inflammation and/or oxidative damage, as well as related compositions, kits, and methods.
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Paragraph 0292; 0306

(2021/04/02)

Synthesis of 1,2,3-triazolyl nucleoside analogues and their antiviral activity
Abstract: Based on the fact that a search for influenza antivirals among nucleoside analogues has drawn very little attention of chemists, the present study reports the synthesis of a series of 1,2,3-triazolyl nucleoside analogues in which a pyrimidine fragment is attached to the ribofuranosyl-1,2,3-triazol-4-yl moiety by a polymethylene linker of variable length. Target compounds were prepared by the Cu alkyne-azide cycloaddition (CuAAC) reaction. Derivatives of uracil, 6-methyluracil, 3,6-dimethyluracil, thymine and quinazolin-2,4-dione with ω-alkyne substituent at the N1 (or N5) atom and azido 2,3,5-tri-O-acetyl-D-β-ribofuranoside were used as components of the CuAAC reaction. All compounds synthesized were evaluated for antiviral activity against influenza virus A/PR/8/34/(H1N1) and coxsackievirus B3. The best values of IC50 (inhibiting concentration) and SI (selectivity index) were demonstrated by the lead compound 4i in which the 1,2,3-triazolylribofuranosyl fragment is attached to the N1 atom of the quinazoline-2,4-dione moiety via a butylene linker (IC50 = 30?μM, SI = 24) and compound 8n in which the 1,2,3-triazolylribofuranosyl fragment is attached directly to the N5 atom of the 6-methyluracil moiety (IC50 = 15?μM, SI = 5). According to theoretical calculations, the antiviral activity of the 1,2,3-triazolyl nucleoside analogues 4i and 8n against H1N1 (A/PR/8/34) influenza virus can be explained by their influence on the functioning of the polymerase acidic protein (PA) of RNA-dependent RNA polymerase (RdRP). Graphic abstract: [Figure not available: see fulltext.]
Andreeva, Olga V.,Garifullin, Bulat F.,Zarubaev, Vladimir V.,Slita, Alexander V.,Yesaulkova, Iana L.,Saifina, Liliya F.,Shulaeva, Marina M.,Belenok, Maya G.,Semenov, Vyacheslav E.,Kataev, Vladimir E.
p. 473 - 490
(2020/09/22)

ANTIVIRAL NUCLEOSIDES AND DERIVATIVES THEREOF
Disclosed herein are nucleoside compounds and derivatives thereof, pharmaceutical compositions containing same, and their methods of synthesis. The compounds are useful in treating orthomyxovirus infections, such as influenza infections.
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Page/Page column 44

(2020/08/22)

Synthesis of remdesivir key intermediate 2, 3, 5-tribenzyloxy-D-ribotide-1, 4-lactone
The invention relates to synthesis of a remdesivir key intermediate 2, 3, 5-tribenzyloxy-D-ribotide-1, 4-lactone. The invention discloses a synthesis method of 2, 3, 5-tribenzyloxy-D-ribotide-1, 4-lactone, and belongs to the field of organic synthesis. The method includes: taking D-ribose as an initial raw material, in methanol, using concentrated sulfuric acid as a catalyst, synthesizing a methoxy compound 2, then fully stirring the substances in a saturated sodium hydroxide solution, adding tetrahydrofuran and n-butylammonium hydrogen sulfate, and then adding benzyl bromide to synthesize a compound 3, dissolving the compound 3 in tetrahydrofuran and then performing catalysis with concentrated sulfuric acid, and performing reflux stirring overnight treatment to obtain a compound 4, dissolving the compound 4 into dichloromethane and water, adding sodium bicarbonate and TEMPO, slowly adding sodium hypochlorite at 0DEG C, raising the temperature to room temperature, and conducting stirring overnight treatment to obtain a compound 5. The method has the characteristics of easily available raw materials and low production cost, each process step is simple and easy to treat, the yield ofthe whole route reaches 43% or above, industrial production is easy to realize, and a basis is provided for industrialization of remdesivir and subsequent derivatives thereof.
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Paragraph 0018-0021

(2020/07/21)

Manno- epi-cyclophellitols Enable Activity-Based Protein Profiling of Human α-Mannosidases and Discovery of New Golgi Mannosidase II Inhibitors
Golgi mannosidase II (GMII) catalyzes the sequential hydrolysis of two mannosyl residues from GlcNAcMan5GlcNAc2 to produce GlcNAcMan3GlcNAc2, the precursor for all complex N-glycans, including the branched N-glycans associated with cancer. Inhibitors of GMII are potential cancer therapeutics, but their usefulness is limited by off-target effects, which produce α-mannosidosis-like symptoms. Despite many structural and mechanistic studies of GMII, we still lack a potent and selective inhibitor of this enzyme. Here, we synthesized manno-epi-cyclophellitol epoxide and aziridines and demonstrate their covalent modification and time-dependent inhibition of GMII. Application of fluorescent manno-epi-cyclophellitol aziridine derivatives enabled activity-based protein profiling of α-mannosidases from both human cell lysate and mouse tissue extracts. Synthesized probes also facilitated a fluorescence polarization-based screen for dGMII inhibitors. We identified seven previously unknown inhibitors of GMII from a library of over 350 iminosugars and investigated their binding modalities through X-ray crystallography. Our results reveal previously unobserved inhibitor binding modes and promising scaffolds for the generation of selective GMII inhibitors.
Aerts, Johannes M. F. G.,Armstrong, Zachary,Beenakker, Thomas J. M.,Boot, Rolf G.,Codée, Jeroen D. C.,Davies, Gideon J.,De Boer, Casper,Debets, Marjoke F.,Florea, Bogdan I.,Geurink, Paul P.,Hissink, Colin,Johnson, Rachel,Kuo, Chi-Lin,Lahav, Dani?l,Liu, Bing,Ovaa, Huib,Overkleeft, Herman S.,Van Der Marel, Gijsbert M.,Van Der Stelt, Mario,Van Rijssel, Erwin R.,Wong, Chung-Sing,Wu, Liang
supporting information
p. 13021 - 13029
(2020/09/01)

Substituted pyrazole compound, preparation method, pharmaceutical composition and applications thereof
The invention discloses a substituted pyrazole compound represented by a formula I, and a preparation method, a pharmaceutical composition and applications thereof, wherein the compound has characteristics of good stability, excellent solubility, low cytotoxicity and remarkable neuroprotective effect, can effectively prevent and treat nerve cell injury, and is an ideal medicinal compound for preventing or treating cerebral stroke, cerebral embolism, cerebral stroke sequelae, cerebral stroke dyskinesia, mitochondrial encephalomyopathy and amyotrophic lateral sclerosis of spinal cord.
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Paragraph 0378-0382

(2020/03/12)

2-Hydroxyimino-6-aza-pyrimidine nucleosides: Synthesis, DFT calculations, and antiviral evaluations
The global public health concerns and economic impact caused by emerging outbreaks of RNA viruses call for the search for new direct acting antiviral agents. Herein, we describe the synthesis, DFT calculations, and antiviral evaluation of a series of novel 2-hydroxyimino-6-aza-pyrimidine ribonucleosides. DFT//B3LYP/6-311+G?? calculations of the tautomeric distributions of the 2-hydroxyimino nucleosides 7, 8, and 9 in aqueous environments indicate a predominance of the canonical 2-(E)-hydroxyimino structure, where the hydroxyl group points away from the sugar moiety. The conformer distributions of the latter geometrical isomers of 7, 8, and 9 support the formation of five membered rings via hydrogen bonding between the (E)-C2N-O-H moiety and N3-H of 7 and 8 and between (E)-C2N-O-H and N3 of 9, creating purine shaped nucleosides with the glycosidic linkage at the pyrimidine ring. The newly synthesized nucleosides were screened against an RNA viral panel, of which moderate antiviral activity was observed against Zika virus (ZIKV) and human respiratory syncytial virus (HRSV). 6-Aza-2-hydroxyimino-5-methyluridine derivative 18 showed activity against ZIKV (EC50 3.2 μM), while its peracetylated derivative 19 showed activity against HRSV (EC50 5.2 μM). The corresponding 4-thiono-2-hydroxyimino derivative 8 showed activity against HRSV (EC50 6.1 μM) and against ZIKA (EC50 2.4 μM). This study shows that the 6-aza-2-hydroxyimino-5-methyluracil derived nucleosides can be further optimized to provide potent antiviral agents. This journal is
Abou-Elkhair, Reham A. I.,Wasfy, Abdalla A.,Mao, Song,Du, Jinxi,Eladl, Sobhy,Metwally, Kamel,Hassan, Abdalla E. A.,Sheng, Jia
p. 19650 - 19662
(2020/12/05)

Glycosides and Glycoconjugates of the Diterpenoid Isosteviol with a 1,2,3-Triazolyl Moiety: Synthesis and Cytotoxicity Evaluation
Several glycoconjugates of the diterpenoid isosteviol (16-oxo-ent-beyeran-19-oic acid) with a 1,2,3-triazolyl moiety were synthesized, and their cytotoxicity was evaluated against some human cancer and normal cell lines. Most of the synthesized compounds demonstrated weak inhibitory activities against the M-HeLa and MCF-7 human cancer cell lines. Three lead compounds, 54, 56 and 57, exhibited high selective cytotoxic activity against M-HeLa cells (IC50 = 1.7-1.9 μM) that corresponded to the activity of the anticancer drug doxorubicin (IC50 = 3.0 μM). Moreover, the lead compounds were not cytotoxic with respect to a Chang liver human normal cell line (IC50 > 100 μM), whereas doxorubicin was cytotoxic to this cell line (IC50 = 3.0 μM). It was found that cytotoxic activity of the lead compounds is due to induction of apoptosis proceeding along the mitochondrial pathway. The present findings suggest that 1,2,3-triazolyl-ring-containing glycoconjugates of isosteviol are a promising scaffold for the design of novel anticancer agents.
Andreeva, Olga V.,Garifullin, Bulat F.,Sharipova, Radmila R.,Strobykina, Irina Yu.,Sapunova, Anastasiya S.,Voloshina, Alexandra D.,Belenok, Mayya G.,Dobrynin, Alexey B.,Khabibulina, Leysan R.,Kataev, Vladimir E.
p. 2367 - 2380
(2020/08/28)

Method for preparing 1-O-acetyl-2, 3, 5-tri-O-benzoyl-1-beta-D-ribofuranose
The invention relates to the field of organic synthesis, in particular to a method for preparing 1-O-acetyl-2, 3, 5-tri-O-benzoyl-1-beta-D-ribofuranose, which comprises the following steps: mixing D-ribose with methanol and a catalyst, heating to react, neutralizing, and concentrating to obtain a methyl esterification intermediate III; mixing the methyl esterification intermediate III with an organic solvent, 4-dimethylaminopyridine and an acid-binding agent, cooling, dropwise adding benzoyl chloride for reaction, washing with water for layering, and drying to obtain a benzoylated intermediateII; finally, mixing the benzoylated intermediate II with an organic solvent and acetic anhydride, then adding a catalyst, stirring, carrying out heat preservation reaction for 10-20 hours at the temperature of 0-70 DEG C, and after the reaction is qualified, cooling, crystallizing and centrifuging to obtain a crude product; finally, performing recrystallization and centrifugal drying to obtain the 1-O-acetyl-2, 3, 5-tri-O-benzoyl-1-beta-D-ribofuranose, and obtaining the 1-O-acetyl-2, 3, 5-tri-O-benzoyl-1-beta-D-ribofuranose. The method has the advantages of short reaction steps, high chemicaland optical purity, simple operation, easily available raw materials, low cost, small amount of three wastes, environmental friendliness and the like, and is suitable for industrial production.
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Paragraph 0028-0029; 0033-0034; 0038-0039; 0043-0044

(2020/08/18)

Methyl glycosides via Fischer glycosylation: translation from batch microwave to continuous flow processing
Abstract: A continuous flow procedure for the synthesis of methyl glycosides (Fischer glycosylation) of various monosaccharides using a heterogenous catalyst has been developed. In-depth analysis of the isomeric composition was undertaken and high consistency with corresponding results observed under microwave heating was obtained. Even in cases where addition of water was needed to achieve homogeneity—a prerequisite for the flow experiments—no detrimental effect on the conversion was found. The scalability was demonstrated on a model case (mannose) and as part of the target-oriented synthesis of d-glycero-d-manno heptose, both performed on multigram scale.
Aronow, Jonas,Stanetty, Christian,Baxendale, Ian R.,Mihovilovic, Marko D.
p. 11 - 19
(2018/11/27)

A novel and environmental friendly synthetic route for hydroxypyrrolidines using zeolites
A critical step in the synthesis of the hydroxypyrrolidines, 1,4-dideoxy-1,4-imino-L-lyxitol and 1,4-dideoxy-1,4-imino-D-lyxitol, from the corresponding D-sugars is the synthesis of O-methyl 2,3-O-isopropylidenepentofuranoses. Instead of applying homogeneous catalysis process with conventional inorganic acid catalysts like HCl and HClO4, it was found that heterogeneous catalysis using zeolites could be used for the one-pot synthesis of O-methyl 2,3-O-isopropylidenepentofuranoses directly from D-sugars, MeOH and acetone at mild condition. The best catalyst was H-beta zeolite containing a Si/Al molar ratio of 150, where a yield of >83% was obtained. The overall yields of the five-step procedure to 1,4-dideoxy-1,4-imino-L-lyxitol and 1,4-dideoxy-1,4-imino-D-lyxitol were 57% and 50%, respectively. This synthetic procedure has several advantages such as competitive overall yield, reduced number of steps, and mild reaction conditions. Furthermore, the zeolite catalyst can be easily recovered from the reaction mixture and reused with no loss of activity.
Fan,Chuah,Jaenicke, Stephan
p. 103 - 114
(2018/12/13)

Synthesis, Reactivity, and Stereoselectivity of 4-Thiofuranosides
Thiosugars, sugars that have their endocyclic oxygen substituted for a sulfur atom, have been used as stable bioisosteres of naturally occurring glycans because the thiosugar glycosydic linkage is supposed to be stabilized toward chemical and enzymatic hydrolysis. We have performed an in-depth investigation into the stability and reactivity of furanosyl thiacarbenium ions, by assessing all four diastereoisomeric thiofuranosides experimentally and computationally. We show that all furanosyl thiacarbenium ions react in a 1,2-cis-selective manner with triethylsilane, reminiscent of their oxo counterparts. The computed conformational space occupied by the thiacarbenium ions is strikingly similar to that of the corresponding furanosyl oxycarbenium ions, indicating that the stereoelectronic substituent effects governing the stability of furanosyl oxocarbenium ions and thiacarbenium ions are very similar. While the thio-ribo-furanose appears to be less reactive than its oxo counterpart, the thio-ara-, lyxo-, and xylo-furanosides appear to be more reactive than their oxygen equivalents. These differences are accounted for using the conformational preference of the donors and the carbocation intermediates. The lower reactivity of the thio-ribo furanosides in (Lewis) acid-mediated reactions and the similarity of the thia- and oxocarbenium ions make thio-ribo-furanosides excellent stabilized analogues of the naturally occurring ribo-furanose sugars.
Madern, Jerre M.,Hansen, Thomas,Van Rijssel, Erwin R.,Kistemaker, Hans A.V.,Van Der Vorm, Stefan,Overkleeft, Herman S.,Van Der Marel, Gijsbert A.,Filippov, Dmitri V.,Codée, Jeroen D.C.
p. 1218 - 1227
(2019/01/25)

3-Trifluoromethylpyrazolones derived nucleosides: Synthesis and antiviral evaluation
Dengue (DENV) viral infection is a global public health problem that infrequently develops life threatening diseases such as dengue hemorrhagic fever (DFS) and dengue shock syndrome (DSS). Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic human corona virus with 38% fatality rate of infected patients. A series of 4-arylhydrazono-5-trifluoromethyl-pyrazolones, their ribofuranosyl, and 5′-deoxyribofuranosyl nucleosides were synthesized, geometry optimized using Density functional theory (DFT), and evaluated for their antiviral activity. 2-Nitrophenylhydrazonopyra-zolone derivative 5 showed significant activity against MERS-CoV (EC50 = 4.6 μM). The nucleoside analog 8 showed moderate activity against DENV-2 (EC50 = 10 μM), while the activity was abolished with the corresponding 5′-deoxyribonucleoside analogs. The identified hits in this study set this category of compounds for further future optimizations.
Ahmed, Ayman M. S.,Abou-Elkhair, Reham A. I.,El-Torky, Alaa M.,Hassan, Abdalla E. A.
p. 590 - 603
(2019/04/03)

COMPOUNDS, PHARMACEUTICAL COMPOSITIONS AND USE THEREOF AS INHIBITORS OF RAN GTPASE
Compounds of general formula IA, IB and IC outlined below, including pharmaceutically acceptable salts, solvates and hydrates thereof. Such compounds and pharmaceutical compositions comprising them may be used in medical conditions involving Ran GTPase.
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Paragraph 0071

(2019/04/09)

Preparation process for L-lyxose
The invention belongs to the technical field of L-lyxose preparation, and relates in particular to a preparation process for L-lyxose. The preparation process comprises the following steps: synthesisofzing 1-methyl-D-ribose, synthesis of 2,3-propylidene-methyl-D-ribose, synthesis of 2,3-propylidene-methylsulfonyl-mthyl-D-ribose, and synthesis of 2,3-propylidene-methyl-L-lyxose and L-lyxose. Thepreparation process for the L-lyxose takes D-ribose as the raw material, and is used for synthesizing L-lyxose by methyl conversion, propylidene conversion, protective group (methylsulfonyl) conversion, and conversion de-protection, so that L-lyxose is prepared through D to L conversion and methyl and propylidene desorption. The whole preparation process is high in catalysisconversion efficiency,is relatively simple in process, adopts cheap and easily available raw materials, is simple and convenient to operate, and is safe; and the obtained product is high in purity.
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Paragraph 0024-0026; 0031-0033; 0038-0040

(2019/02/25)

Phosphorylated Glycoconjugates Based on Isosteviol, d-Arabinofuranose, and d-Ribofuranose
First phosphorylated glycoconjugates were synthesized in three stages on the basis of isosteviol, d-arabinofuranose, and d-ribofuranose. In the first stage, isosteviol reacted with methyl 5-O-(p-tosyl)-2,3-di-O-benzoyl-d-ribofuranoside and methyl 5-O-(p-tosyl)-2,3-di-O-benzoyl-d-arabinofuranoside to give glycoconjugates in which the diterpenoid fragment is linked through ester bond to the carbohydrate C5 atom. In the second stage, the anomeric methoxy group in the furanoside fragment was replaced by bromine, and the resulting 2,3-di-O-benzoyl-d-ribofuranosyl and 2,3-di-O-benzoyl-d-arabinofuranosyl bromides were treated with dibutyl phosphate to afford the target phosphorylated derivatives.
Sharipova,Belenok,Strobykina, I. Yu.,Kataev
p. 508 - 513
(2019/06/05)

Computer Modelling and Synthesis of Deoxy and Monohydroxy Analogues of a Ribitylaminouracil Bacterial Metabolite that Potently Activates Human T Cells
5-(2-Oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU) is a natural product formed during bacterial synthesis of vitamin B2. It potently activates mucosal associated invariant T (MAIT) cells and has immunomodulatory, inflammatory, and anticancer properties. This highly polar and unstable compound forms a remarkably stable Schiff base with a lysine residue in major histocompatibility complex class I–related protein (MR1) expressed in antigen-presenting cells. Inspired by the importance of the ribityl moiety of 5-OP-RU for binding to both MR1 and the T cell receptor (TCR) on MAIT cells, each OH was removed in silico. DFT calculations and MD simulations revealed a very stable hydrogen bond between the C3′?OH and uracil N1H, which profoundly restricts flexibility and positioning of each ribityl-OH, potentially impacting their interactions with MR1 and TCR. By using deoxygenation strategies and kinetically controlled imine formation, four monodeoxyribityl and four monohydroxyalkyl analogues of 5-OP-RU were synthesised as new tools for probing T cell activation mechanisms.
Ler, Geraldine J. M.,Xu, Weijun,Mak, Jeffrey Y. W.,Liu, Ligong,Bernhardt, Paul V.,Fairlie, David P.
p. 15594 - 15608
(2019/11/16)

Synthesis of novel 1,2,3-triazolyl nucleoside analogues bearing uracil, 6-methyluracil, 3,6-dimethyluracil, thymine, and quinazoline-2,4-dione moieties
A series of novel 1,2,3-triazolyl nucleoside analogues was synthesized via the CuAAC reaction of N1-alkynyl uracil, 6-methyluracil, 3,6-dimethyl uracil, thymine and quinazolin-2,4-dione with protected azido β-D-ribofuranose. The obtained compounds differ in both the nature of the pyrimidine-2,4-dione fragment and the length of the polymethylene linker connecting it with the β-D-ribofuranosyl-1,2,3-triazol-4-yl moiety. The 1,2,3-triazolyl nucleoside analogues were evaluated for their cytotoxicity in vitro.
Andreeva, Olga V.,Belenok, Maya G.,Saifina, Liliya F.,Shulaeva, Marina M.,Dobrynin, Alexey B.,Sharipova, Radmila R.,Voloshina, Alexandra D.,Saifina, Alina F.,Gubaidullin, Aidar T.,Khairutdinov, Bulat I.,Zuev, Yuriy F.,Semenov, Vyacheslav E.,Kataev, Vladimir E.
supporting information

(2019/11/05)

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF
Disclosed herein are nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a Picornaviridae and/or Flaviviridae viral infections with one or more nucleotide analogs.
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Paragraph 0414

(2018/03/06)

COMPOSITION COMPRISING PAEONIFLORIN OR ALBIFLORIN ANALOGUE, METHOD OF PREPARATION THEREOF
A composition comprises a compound of formula (I) and at least one cosmetically acceptable carrier. It can be used for preventing or decreasing skin pigmentation and /or lightening skin tone.
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Page/Page column 18; 19

(2018/04/20)

Selective inhibition of TRPM2 channel by two novel synthesized ADPR analogues
Transient receptor potential melastatin-2 (TRPM2) channel critical for monitoring internal body temperature is implicated in the pathological processes such as neurodegeneration. However, lacking selective and potent TRPM2 inhibitors impedes investigation and validation of the channel as a drug target. To discover novel and selective TRPM2 inhibitors, a series of adenosine 5′-diphosphoribose analogues were synthesized, and their activities and selectivity were evaluated. Whole-cell patch-clamp recordings were employed for screen and evaluation of synthesized compounds. Two compounds, 7i and 8a, were identified as TRPM2 inhibitors with IC50 of 5.7 and 5.4?μm, respectively. Both 7i and 8a inhibited TRPM2 current without affecting TRPM7, TRPM8, TRPV1 and TRPV3. These two TRPM2 inhibitors can serve as new pharmacological tools for further investigation and validation of TRPM2 channel as a drug target, and the summarized structure–activity relationship (SAR) may also provide insights into further improving existing inhibitors as potential lead compounds.
Luo, Xiao,Li, Meng,Zhan, Kaiyu,Yang, Wei,Zhang, Lihe,Wang, KeWei,Yu, Peilin,Zhang, Liangren
p. 552 - 566
(2017/11/21)

Transformation of Sugars into Chiral Polyols over a Heterogeneous Catalyst
Transformation of sugars, while maintaining the intrinsic stereochemical structure, is desirable. However, such a transformation requires multistep synthesis with protection and deprotection of the OH groups. Herein, a new method for selective transformation of sugar derivatives into chiral building blocks and a diol synthon, with retention of the intrinsic configuration (stereo- and regioselectively), is demonstrated. The method is based on the selective recognition of cis-vicinal OH groups in sugars and leads to the one-pot removal of the cis-vicinal OH groups, without protection of OH groups (except the OH group of the hemiacetal group), over a heterogeneous CeO2-supported ReOx and Pd (ReOx-Pd/CeO2) catalyst by using H2 as a reducing agent.
Tamura, Masazumi,Yuasa, Naoto,Cao, Ji,Nakagawa, Yoshinao,Tomishige, Keiichi
supporting information
p. 8058 - 8062
(2018/06/29)

Synthetic process for benzyl ribose lactone
The invention discloses a synthetic process for benzyl ribose lactone, relates to the technical field of medicine synthesis, and solves the technical problems that crystal purification steps in an existing process are complex, and reaction still locking can appear. According to the process, different reagent and solvent are selected, intermediate does not undergo the purification treatment and directly gets into the next step with an oily matter or without further concentration treatment, the intermediate undergoes separation and purification and crystallization at the final step, the processhas the advantages that the purification and crystallization steps are simple, and the problem of the reaction still locking can not appear, the loss is reduced, the yield coefficient reaches to 79%,and the purity reaches to 99% or above; According to the process, the expensive solvent is replaced by the cheap reagent, under the circumstance of not affecting the product quality and yield coefficient, the synthesis cost of the benzyl ribose lactone is reduced.
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Paragraph 0020; 0021; 0022; 0023; 0024; 0025; 0026; 0027

(2018/07/30)

A new process for deprotection of acetyl and benzoyl groups in synthesis of azacitidine
4-Amino-1-β-D-ribofuranosyl-s-triazin-2(1H)-one or azacitidine is a promising DNA demethylation inhibitor used for the treatment of myloneplastic, bone cancer and breast cancer. An efficient, cost-effective and convenient manufacturing process for the synthesis of azacitidine is described. The present research relates to the synthesis, deprotection, isolation and purification of azacitidine (1). In this process, more particularly 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is used as deprotection reagent for deprotection of O-acetyl, O-benzoyl to acquire azacitidine (1). The new process allows for the reliable and efficient production of drug substance similar overall yield. The new improved process has merits including enantiomeric purity, better crystallization and the product complies with the requirements of USP30.
Kumar, Srujana Suneel,Sethuraman
p. 1521 - 1524
(2018/06/12)

A 2-O-Methylriboside Unknown Outside the RNA World Contains Arsenic
Lipid-soluble arsenic compounds, also called arsenolipids, are ubiquitous marine natural products of currently unknown origin and function. In our search for clues about the possible biological roles of these compounds, we investigated arsenic metabolism in the unicellular green alga Dunaliella tertiolecta, and discovered an arsenolipid fundamentally different from all those previously identified; namely, a phytyl 5-dimethylarsinoyl-2-O-methyl-ribofuranoside. The discovery is of particular interest because 2-O-methylribosides have, until now, only been found in RNA. We briefly discuss the significance of the new lipid in biosynthesis and arsenic biogeochemical cycling.
Glabonjat, Ronald A.,Raber, Georg,Jensen, Kenneth B.,Guttenberger, Nikolaus,Zangger, Klaus,Francesconi, Kevin A.
supporting information
p. 11963 - 11965
(2017/09/06)

Preparation method of tribenzoyl cytidine
The invention belongs to the field of medical chemistry, and in particular relates to a preparation method of tribenzoyl cytidine. According to the method, the tribenzoyl cytidine is prepared from D-furanose serving as a raw material by the reaction steps of methylation, hydroxyl group protection, oxidation, Grignard reaction, fluorization, hydroxyl group deprotection, ester production with benzoyl chloride, chlorination, reaction with pyrimidine base and the like. The method is simple and convenient to operate, mild in reaction condition, high in yield and purity, and favorable for industrialized mass production.
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Paragraph 0048; 0049; 0050; 0051

(2017/08/28)

Larger laboratory scale synthesis of 5-methyluridine and formal synthesis of its L-enantiomer
A larger laboratory scale synthesis (>60 g per run) of 5-methyluridine is presented. The critical intermediate 1,2-O-isopropylidene-α-D-ribofuranose was prepared from very cheap D-glucose via D-allose. Its L-enantiomer was obtained from L-arabinose via L-glucose, and also from L-xylose. {figure presented}.
Thiesen, Luciano J. Hoeltgebaum,Cabral, Nadia,Joselice E Silva, Maria,Bezerra, Gilson,Doboszewski, Bogdan
p. 249 - 264
(2017/06/19)

A method for preparing rope fluorine cloth Wei (by machine translation)
The invention relates to the field of medical technology, in particular to a method for preparing rope fluorine cloth Wei, the method to D - ribose as the starting material, through the esterification reaction, hydroxy protecting reaction, hydroxy oxidation reaction, the methylation reaction, the fluorination reaction, butt reaction, hydrolysis, connected with the phosphoric acid ester side chain such as a series of reaction, the product finally obtained rope fluorine cloth Wei. The preparation of the invention rope fluorine cloth Wei method to D - ribose as the raw material, the raw materials and the cost is low, the reaction in step hydrolysis of few reaction steps, easy industrialization. (by machine translation)
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Paragraph 0027; 0028; 0036; 0037

(2017/08/28)

Discovery of 2'-α-C-Methyl-2'-β-C-fluorouridine Phosphoramidate Prodrugs as Inhibitors of Hepatitis C Virus
2′-α-C-Methyl-2′-β-C-fluorouridine and its phosphoramidate prodrugs were synthesized and evaluated for their inhibitory activity against HCV. The structure?activity relationship analysis of the phosphoramidate moiety found that 17m, 17q, and 17r exhibit potent activities against HCV, with EC50 values of 1.82 ± 0.19, 0.88 ± 0.12, and 2.24 ± 0.22 μM, respectively. The docking study revealed that the recognition of the 2′-β-F by Arg158, 3′-OH by N291, and the Watson?Crick pairing with the template allowed 23 to form the in-line conformation necessary for its incorporation into the viral RNA chain.
Zeng, Debin,Zhang, Rui,Nie, Quandeng,Cao, Lin,Shang, Luqing,Yin, Zheng
supporting information
p. 1197 - 1201
(2016/12/18)

Benzylidene Acetal Protecting Group as Carboxylic Acid Surrogate: Synthesis of Functionalized Uronic Acids and Sugar Amino Acids
Direct oxidation of the 4,6-O-benzylidene acetal protecting group to C-6 carboxylic acid has been developed that provides an easy access to a wide range of biologically important and synthetically challenging uronic acid and sugar amino acid derivatives in good yields. The RuCl3-NaIO4-mediated oxidative cleavage method eliminates protection and deprotection steps and the reaction takes place under mild conditions. The dual role of the benzylidene acetal, as a protecting group and source of carboxylic acid, was exploited in the efficient synthesis of six-carbon sialic acid analogues and disaccharides bearing uronic acids, including glycosaminoglycan analogues.
Banerjee, Amit,Senthilkumar, Soundararasu,Baskaran, Sundarababu
supporting information
p. 902 - 906
(2016/01/16)

Magnesium pyrophosphates in enzyme mimics of nucleotide synthases and kinases and in their prebiotic chemistry
Derivatives of ribosyl pyrophosphate have been synthesized, and examined with magnesium salts in the coupling of the ribose unit to various nucleophiles, including pyrazole and 2-chloroimidazole. Only with the magnesium salt present did they generate the ribosyl cation by binding to the leaving group and then couple the ribose derivative with nucleophiles. The role of magnesium salts in phosphorylation of methanol by ATP was also examined. Here a remarkable effect was seen: phosphorylation by ATP was slowed with low concentrations of Mg2+ but accelerated by higher concentrations. Related effects were also seen in the effect of Mg2+ on phosphorylation by ADP. The likely mechanisms explain these effects.
Gopinath, Purushothaman,Ramalingam, Vijayakumar,Breslow, Ronald
p. 12011 - 12014
(2015/10/12)

Synthesis and biological activity of reversed pyrimidine nucleosides
An efficient approach to reversed nucleosides which enables their synthesis in gram quantities is described. N-1′-Pyrimidine reversed nucleosides were prepared by treating of the sodium salt of pyrimidine bases with protected 5-tosyl ribose. Additionally, N-1′,N-3′-disubstituted reversed nucleosides were isolated in the condensation reactions with the 5-halogen pyrimidines. Using the Sonogashira coupling of 5′-iodouracil reversed nucleoside with ethynyltrimethyl silane gave 5′-ethynyl derivative which was further transformed into 5′-acetyl reversed nucleoside. Biological activity of deprotected reversed nucleosides was validated on the panel of six human carcinoma cell lines (HeLa, MIAPaCa2, Hep2, NCI-H358, CaCo-2, and HT-29). 5′-Iodouracil derivative displayed moderate growth inhibition activity against human colon carcinoma (CaCo-2) cells.
?upan?i?, Nata?a,Ban, ?eljka,Mati?, Josipa,Safti?, Dijana,Glava?-Obrovac, Ljubica,?ini?, Biserka
p. 43 - 52
(2015/05/27)

Synthesis of well-defined adenosine diphosphate ribose oligomers
The post-translational modification of proteins that is known as adenosine diphosphate ribosylation (ADPr) regulates a wide variety of important biological processes, such as DNA-damage repair and cellular metabolism. This modification is also involved in carcinogenesis and the process of aging. Therefore, a better understanding of the function of ADP-ribosylation is crucial for the development of novel therapeutics. To facilitate the elucidation of the biology of ADPr, the availability of well-defined fragments of poly(ADP-ribose) is essential. Herein we report a solid-phase synthetic approach for the preparation of ADP-ribose oligomers of exactly defined length. The methodology is exemplified by the first reported synthesis of an ADP-ribose dimer and trimer.
Kistemaker, Hans A. V.,Lameijer, Lucien N.,Meeuwenoord, Nico J.,Overkleeft, Herman S.,Van Der Marel, Gijsbert A.,Filippov, Dmitri V.
supporting information
p. 4915 - 4918
(2015/04/14)

Replacement of water molecules in a phosphate binding site by furanoside-appended lin-benzoguanine ligands of tRNA-guanine transglycosylase (TGT)
The enzyme tRNA-guanine transglycosylase has been identified as a drug target for the foodborne illness shigellosis. A key challenge in structure-based design for this enzyme is the filling of the polar ribose-34 pocket. Herein, we describe a novel series of ligands consisting of furanoside-appended lin-benzoguanines. They were designed to replace a conserved water cluster and differ by the functional groups at C(2) and C(3) of the furanosyl moiety being either OH or OMe.The unfavorable desolvation of Asp102 and Asp280, which are located close to the ribose-34 pocket, had a significant impact on binding affinity. While the enzyme has tRNA as its natural substrate, X-ray co-crystal structures revealed that the furanosyl moieties of the ligands are not accommodated in the tRNA ribose-34 site, but at the location of the adjacent phosphate group. A remarkable similarity of the position of the oxygen atoms in these two structures suggests furanosides as a potential phosphate isoster.
Barandun, Luzi J.,Giroud, Maude,Grünenfelder, Claudio,Schweizer, W. Bernd,Bernet, Bruno,Diederich, Franois,Ehrmann, Frederik R.,Immekus, Florian,Betz, Michael,Heine, Andreas,Klebe, Gerhard,Zimmerli, Daniel
supporting information
p. 126 - 135
(2015/02/18)

Galacto configured N-aminoaziridines: A new type of irreversible inhibitor of β-galactosidases
A new type of galactose mimetics has been synthesized following a straightforward synthetic approach based on cyclohexene olefin aziridination reactions directed by hydroxyl substituents. These enantiomerically pure galacto-configured N-aminoaziridines are potent irreversible inhibitors of Aspergillus oryzae and Escherichia coli β-galactosidases.
Alcaide, Anna,Trapero, Ana,Pérez, Yolanda,Llebaria, Amadeu
supporting information
p. 5690 - 5697
(2015/05/27)

Iodine monochloride (ICl) as a highly efficient, green oxidant for the oxidation of alcohols to corresponding carbonyl compounds
Iodine monochloride (ICl) was discovered to be a highly efficient, green oxidant, which can oxidize aldose hemiacetals, diarylmethanols, arylalkylmethanols, anddialkylmethanols to the corresponding aldose lactones, diarylmethanones, arylalkylmethanones, and dialkylmethanones, respectively, in high yields. ICl as a green, metal-free oxidant is characterized by mild reaction condition, short reaction time, good yield, and broad scope.
Wei, Peng,Zhang, Datong,Gao, Zhigang,Cai, Wenqing,Xu, Weiren,Tang, Lida,Zhao, Guilong
supporting information
p. 1457 - 1470
(2015/05/20)

Anaerobic 5-Hydroxybenzimidazole Formation from Aminoimidazole Ribotide: An Unanticipated Intersection of Thiamin and Vitamin B12 Biosynthesis
Comparative genomics of the bacterial thiamin pyrimidine synthase (thiC) revealed a paralogue of thiC (bzaF) clustered with anaerobic vitamin B12 biosynthetic genes. Here we demonstrate that BzaF is a radical S-adenosylmethionine enzyme that catalyzes the remarkable conversion of aminoimidazole ribotide (AIR) to 5-hydroxybenzimidazole (5-HBI). We identify the origin of key product atoms and propose a reaction mechanism. These studies represent the first step in solving a long-standing problem in anaerobic vitamin B12 assembly and reveal an unanticipated intersection of thiamin and vitamin B12 biosynthesis.
Mehta, Angad P.,Abdelwahed, Sameh H.,Fenwick, Michael K.,Hazra, Amrita B.,Taga, Michiko E.,Zhang, Yang,Ealick, Steven E.,Begley, Tadhg P.
supporting information
p. 10444 - 10447
(2015/09/28)

Amphidinins C-F, amphidinolide Q analogues from marine dinoflagellate Amphidinium sp.
Four new polyketides, amphidinins C-F (1-4), have been isolated from the culture broth of symbiotic dinoflagellate Amphidinium sp. The analysis of their spectral data revealed that amphidinins C-F (1-4) were 4,5-seco-analogues of amphidinolide Q (5). The absolute configurations of the new compounds were elucidated by the combination of J-based configuration analysis, modified Mosher's method, and chemical derivatization. Amphidinins D (2) and F (4) are the first glycosides related to amphidinolides. Amphidinins C-F (1-4) showed antimicrobial activity against bacteria and/or fungi.
Kubota, Takaaki,Iwai, Takahiro,Sakai, Kanae,Gonoi, Tohru,Kobayashi, Jun'ichi
supporting information
p. 5624 - 5627
(2015/02/19)

Gold(III)-catalyzed glycosidations for 1,2- trans and 1,2- cis furanosides
Stereoselective synthesis of furanosides is still a daunting task, unlike the pyranosides, for which several methods exist. Herein, a unified stereoselective strategy for the synthesis of 1,2-trans and 1,2-cis furanosides is revealed for seven out of eight possible isomers of pentoses. The identified protocol gives access to diastereoselective synthesis of α- and β-araf, ribf, lyxf, and α-xylf furanosides. 1,2-trans glycosides were synthesized by the use of propargyl 1,2-orthoesters under gold-catalyzed glycosidation conditions, and subsequently, they are converted into 1,2-cis glycosides through oxidation-reduction as the key functional group transformation. All the reactions are found to be fully diastereoselective, mild, and high yielding.
Thadke, Shivaji A.,Mishra, Bijoyananda,Hotha, Srinivas
p. 7358 - 7371
(2014/09/29)

Synthesis of 2,3-O-benzyl-ribose and xylose and their equilibration
The preparation and NMR analysis of 2,3-di-O-benzyl d-ribose and 2,3-di-O-d-xylose are described. In DMSO-d6 the sugars adopt a conformation in which the hydroxyl groups are in an equatorial position. In CDCl3 and CD2Cl2 the sugars adopts a conformation in which intramolecular hydrogen bonding plays an important role in determining the equilibrium composition. These findings were also confirmed by DFT studies and, in the solid phase, by X-ray single crystal diffraction.
Jeffrey, Reignier,Singh, Gurdial,Plaza-Alexander, Patrice G.J.,Singh, Nadia,Goodman, Jonathan M.,Bacchi, Alessia,Punzo, Francesco
p. 1424 - 1429
(2014/12/11)

Synthesis of C-spiro-glycoconjugates from sugar lactones via zinc mediated Barbier reaction
Anomeric gem-diallylation, mono-β-crotylation and mono-β- propargylation of sugar 1,5 and 1,4 lactones have been achieved under Barbier reaction conditions using Zn powder and a catalytic amount of TMSCl as an activator. Ring closing olefin metathesis of the synthesized gem-diallyl derivatives furnished C-spiro cyclopentene glycosides. Finally, the cyclopentene rings were converted into carbohydrate based tricyclic morpholine fused triazole glycoconjugates as potential SGLT2 inhibitors.
Lambu, Mallikharjuna Rao,Hussain, Altaf,Sharma, Deepak K.,Yousuf, Syed Khalid,Singh, Baldev,Tripathi, Anil. K.,Mukherjee, Debaraj
p. 11023 - 11028
(2014/03/21)

Synthesis of cyclophellitol, cyclophellitol aziridine, and their tagged derivatives
Cyclitol epoxides and aziridines are potent and selective irreversible inhibitors of retaining glycosidases. We have previously reported on our studies on the use of activity-based probes derived from cyclophellitol and from its aziridine analogue for activity-based profiling of retaining β-glucosidases in vitro, in situ, and in some examples also in vivo. In this work we disclose full details of the synthesis, purification, and analysis of a comprehensive panel of cyclophellitol analogues, all featuring the β-glucose configuration and designed as tools for selective inhibition and/or imaging of human acid glucosylceramidase (epoxides) or as broad-spectrum probes for retaining β-glucosidases (aziridines).
Li, Kah-Yee,Jiang, Jianbing,Witte, Martin D.,Kallemeijn, Wouter W.,Van Den Elst, Hans,Wong, Chung-Sing,Chander, Sharina D.,Hoogendoorn, Sascha,Beenakker, Thomas J. M.,Codée, Jeroen D. C.,Aerts, Johannes M. F. G.,Van Der Marel, Gijs A.,Overkleeft, Herman S.
p. 6030 - 6043
(2015/03/30)

α-selective ribofuranosylation of alcohols with ribofuranosyl iodides and triphenylphosphine oxide
Ribofuranosylation of a variety of alcohols with ribofuranosyl iodides in the presence of a base and triphenylphosphine oxide afforded the corresponding α-ribofuranosides with diastereoselectivities ≥ 99:1. This reaction can be carried out under mildly basic conditions and is thus compatible with acid-sensitive functional groups.
Oka, Natsuhisa,Kajino, Rin,Takeuchi, Kaoru,Nagakawa, Haruna,Ando, Kaori
p. 7656 - 7664
(2014/10/15)

Facile synthesis of β- And α-arabinofuranosides and application to cell wall motifs of M. tuberculosis
Propargyl 1,2-orthoesters of arabinose are exploited for the synthesis of 1,2-trans furanosides; easily accessible 1,2-trans ribofuranosides are converted to challenging 1,2-cis-arabinofuranosides by oxidoreduction. Utility of these protocols was demonstrated by the successful synthesis of major structural motifs present in the cell surface of Mycobacterium tuberculosis. Key furanosylations were carried out under gold-catalyzed glycosidation conditions.
Thadke, Shivaji A.,Mishra, Bijoyananda,Hotha, Srinivas
supporting information
p. 2466 - 2469
(2013/06/27)

A Reverse Strategy for synthesis of nucleosides based on n-pentenyl orthoester donors
Strategically derivatized NPOE glycosyl donors, are able to efficiently glycosylate silylated nucleobases under mild conditions, even as low as -78°C if necessary. Ensuring trans-1,2 glycosylation, thus permitting, unlike classical procedures, a Reverse Strategy for the synthesis of ribonucleosides, where glycosylation occurs late, rather than early, and convergency is optimized.
Fraser-Reid, Bert,Ganney, Parimala,Ramamurty, Changalvala V. S.,Gomez, Ana M.,Lopez, J. Cristobal
supporting information
p. 3251 - 3253
(2013/05/08)

Convenient strategy for the synthesis of highly functionalizable hydroxylated unsaturated azepanes
A convenient approach to the construction of dihydroxylated unsaturated azepanes featuring a functional group (ethoxycarbonyl)methyl or (cyano)methyl at C-2 was achieved from a pent-4-enal synthon obtained in four steps from d-xylose. The key step of the sequence relied on the conjugate addition of allylamine to α,β-unsaturated ester or nitrile, prepared by Wadsworth-Emmons olefination. Subsequent RCM afforded the target unsaturated azepanes.
Goumain, Sophie,Taghzouti, Hanaa,Portella, Charles,Behr, Jean-Bernard,Plantier-Royon, Richard
scheme or table
p. 4440 - 4443
(2012/09/25)