cas 4137-56-8, Methyl 2,3-O-isopropylidene-5-O-(p-tolylsulfonyl)-beta-D-ribofuranoside

Articles about 4137-56-8Total 41 be found

Article title
Article abstract
Author
Journal number and time
Download

[18F]-5-Fluoro-5-deoxyribose, an efficient peptide bioconjugation ligand for positron emission tomography (PET) imaging
[18F]-5-Fluoro-5-deoxyribose ([18F]-FDR) conjugates much more rapidly than [18F]-FDG under mild reaction conditions to peptides and offers new prospects for mild and rapid bioconjugation for fluorine-18 labelling in PET imaging.
Li, Xiang-Guo,Dall'Angelo, Sergio,Schweiger, Lutz F.,Zanda, Matteo,O'Hagan, David
p. 5247 - 5249
(2012)
Read Online

Structure-property relationships of ribose based ionic liquids
The authors of this work have successfully synthesized a broad choice of new ribose based ionic liquids, using several varying protecting groups (methyl, ethyl, allyl and benzyl) at the various positions of the carbohydrate, as well as different quarternised N-heterocycles and different anions. These consistent variations of the carbohydrate based ionic liquids (CHILs) enabled an extensive structure-property relationship study of thermal properties, allowing the authors to prove existing trends and to find a correlation between the decomposition temperature and the structure of the CHILs.
Jopp, Stefan,Komabayashi, Mirai,Stiller, Tanja
(2021/01/11)

A facile ultrasound-assisted synthesis of methyl 2,3-O-isopropylidene-β-D-ribofuranoside from D-ribose and its use to prepare new 1,2,3-triazole glycoconjugates
The conversion of D-ribose into its 2,3-O-isopropylidene derivative using ultrasonic irradiation is described. The ultrasound proved to be an excellent alternative as the energy source for the reaction. Different reaction times were investigated, and shorter reaction times and high yield were achieved without the need for purification of the acetonide. The compound was then applied as the starting material in the synthesis of 23 new glycoconjugates of 1,2,3-triazole that are tethered together in different ways. The synthesized compounds were characterized by FTIR, 1H NMR, 13C NMR, and HRMS techniques.
Evangelista, Tereza Cristina Santos,Aquino, Gabriel Alves Souto de,Donza, Marcio Roberto H.,Leit?o, Rafael Lisboa,Carvalho, Victor Salarolli de,Kaiser, Carlos Roland,Ferreira, Sabrina Baptista
p. 243 - 268
(2021/10/23)

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.
-
(2021/04/02)

Synthesis and biological evaluation of benzo[f]indole-4,9-diones n-linked to carbohydrate chains as new type of antitumor agents
In this work, we report the synthesis of three series of carbohydrate-based benzo[f]indole-4,9-diones and amino-1,4-naphthoquinone derivatives and evaluated their cytotoxic activity against eight human cancer cell lines. Several compounds showed a promising cytotoxic activity toward the tumor cell lines (half maximal inhibitory concentration (IC50) 10.0 μM). The importance of the substitution pattern of the quinone derivatives on the antitumor activity was also discussed. 3-Carboethoxy-2-methyl-benzo[f]indole-4,9-dione derivatives were more cytotoxic than their parent compounds and amino-1,4-naphthoquinones. Unlike clinically useful anticancer agent doxorubicin, the majority of synthesized compounds did not exhibit any lytic effects against erythrocytes or normal human leukocytes.
Dias, Flaviana R.F.,Guerra, Fabiana S.,Lima, Fernanda A.,de Castro, Yasmin K.C.,Ferreira, Vitor F.,Campos, Vinícius R.,Fernandes, Patrícia D.,Cunha, Anna C.
p. 476 - 489
(2021/02/12)

The quaternization reaction of 5-o-sulfonates of methyl 2,3-o-isopropylidene-β-D-ribofuranoside with selected heterocyclic and aliphatic amines
The synthesis of N-((methyl 5-deoxy-2,3-O-isopropylidene-β-D-ribofuranoside)-5-yl) ammoniumsalts are presented. To determine the effect of the nucleophile type and outgoing group on the quaternization reaction, selected aliphatic and heterocyclic aromatic amines reacted with: methyl 2,3-O-isopropylidene-5-O-tosyl-β-D-ribofuranoside or methyl 2,3-O-isopropylidene-5-O-mesyl-β-D -ribofuranoside ormethyl 2,3-O-isopropylidene-5-O-triflyl-β-D-ribofuranosidewere performed on amicro scale. High-resolution 1H- and 13C-NMRspectraldata for all newcompoundswere recorded. Additionally, the single-crystalX-raydiffraction analysis formethyl 2,3-O-isopropylidene-5-O-mesyl-β-D-ribofuranoside and selected in silico interaction models are reported.
?lusarz, Rafa?,Chojnacki, Jaros?aw,Dmochowska, Barbara,Madaj, Janusz,Samaszko-Fiertek, Justyna
(2020/05/13)

New glycosylated platinum(II) phthalocyanine containing ribose moiety – synthesis and photophysical properties
The synthesis and spectral characterisation of new glycoconjugated phthalonitrile connected with triazole linker via Cu(II)-mediated click reaction is reported. Treatment of azido derivative of 1-methoxy-2,3- O-isopropylidene-β-D-ribose with 4-O-propargyloxy-substituted phthalonitrile in presence copper(II) sulfate pentahydrate and sodium L-ascorbate in tert-butanol/water gave desired glycophthalonitrile with 84% yield. This precursor underwent mixed-cyclisation with the tert-butyl-substituted phthalonitrile, to afford the mono-glycosylated A3B-type platinum(II) phthalocyanine. Upon irradiation this compound could sensitise the formation of singlet oxygen in acetone, with 0.95 quantum yield by comparative method with use of 1,3-diphenylisobenzofuran (DPBF) as scavenger.
Burtsev, Ivan D.,Volov, Alexander N.
(2020/07/04)

Industrial large-scale production method of capecitabine intermediate
The invention provides an industrial large-scale production method of a capecitabine intermediate. The industrial large-scale production method adopts a one-pot production method of simultaneously adding methanol and acetone, and is a preparation method which is energy-saving, short in production period and high in yield; a method of adding low-boiling-point solvents such as ethyl acetate into dimethyl sulfoxide or pyrrolidone for reflux cooling to take away heat is adopted; and a production method of hydrolyzing while distilling is designed, the methanol and the acetone which are generated byhydrolysis are distilled out, the methanol and the acetone in water are continuously reduced, the reaction is carried out towards K3, and the reaction is complete and thorough.
-
(2020/09/20)

PRMT5 INHIBITORS
The present invention provides a compound of Formula (I) or the pharmaceutically acceptable salts thereof, which are PRMT5 inhibitors.
-
Page/Page column 35; 41

(2020/03/02)

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)

AMPHIPHILE PRODRUGS
Amphiphilic prodrugs of general formula A-X are disclosed, wherein A is a biologically active agent or may be metabolised to a biologically active agent; and X is selected from the group consisting of R, or up to three R moieties attached to a linker, Y1, Y2 or Y3, wherein R is selected from a group consisting of alkyl, alkenyl, alkynyl, branched alkyl, branched alkenyl, branched alkynyl, substituted alkyl, substituted alkenyl and substituted alkynyl groups and their analogues; Y1 is a linker group which covalently attached to an R group at one site and is attached to A at a further independent site; Y2 is a linker group which is covalently attached to two R groups at two independent sites and is attached to A at a further independent site; and Y3 is a linker group which is covalently attached to three R groups at three independent sites and is attached to A at a further independent site. Self-assembly of the amphiphilic prodrugs into reverse lyotropic phases, particularly hexagonal, cubic and sponge, is disclosed. In preferred embodiments A is dopamine or a 5-fluorouracil prodrug.
-
Paragraph 0142; 0145; 0146

(2019/06/12)

Preparation method of high-purity capecitabine key intermediate
The invention discloses a preparation method of a high-purity capecitabine key intermediate. The preparation method comprises the following steps: taking D-ribose as an initial raw material, performing hydroxyl protection, 5-site tosylation, reduction, deprotection and acetylation to obtain high-purity 1,2,3-O-triacetyl-5-deoxo-D-ribose, wherein the 5-site tosylation reaction is carried out in anorganic solvent 1 by adopting inorganic base 1. Meanwhile, the acetylation reaction is carried in the presence of alkali 2 by taking water as a reaction solvent and taking 4-dimethylamiopryidine as acatalyst. The preparation method disclosed by the invention is mild in reaction conditions, high in yield, economic and effective, the purity of the prepared 1,2,3-O-triacetyl-5-deoxo-D-ribose can reach 99.0%, the alpha-isomer is small in content even is not detected, and the preparation method is applicable to large-scale industrial production.
-
Paragraph 0046; 0047; 0048

(2019/03/06)

Adenosine diphosphate ribose compound, preparation method and biological activity thereof
The invention discloses an adenosine diphosphate ribose compound, which has a general formula shown as (I), wherein the definitions of all substituents are detailed in the specification. In addition,the invention also discloses a preparation method and application of the compound. The adenosine diphosphate ribose (ADPR) structural analogue provided by the invention has specific TRPM2 (transient receptor potential melastatin 2) inhibitory activity.
-
(2019/01/24)

Design, synthesis, cholinesterase inhibition and molecular modelling study of novel tacrine hybrids with carbohydrate derivatives
A series of hybrids containing tacrine linked to carbohydrate-based moieties, such as D-xylose, D-ribose, and D-galactose derivatives, were synthesized by the nucleophilic substitution between 9-aminoalkylamino-1,2,3,4-tetrahydroacridines and the corresponding sugar-based tosylates. All compounds were found to be potent inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the nanomolar IC50 scale. Most of the D-xylose derivatives (6a-e) were selective for AChE and the compound 6e (IC50 = 2.2 nM for AChE and 4.93 nM for BuChE) was the most active compound for both enzymes. The D-galactose derivative 8a was the most selective for AChE exhibiting an IC50 ratio of 7.6 for AChE over BuChE. Only two compounds showed a preference for BuChE, namely 7a (D-ribose derivative) and 6b (D-xylose derivative). Molecular docking studies indicated that the inhibitors are capable of interacting with the entire binding cavity and the main contribution of the linker is to enable the most favorable positioning of the two moieties with CAS, PAS, and hydrophobic pocket to provide optimal interactions with the binding cavity. This finding is reinforced by the fact that there is no linear correlation between the linker size and the observed binding affinities. The majority of the new hybrids synthesized in this work do not violate the Lipinski's rule-of-five according to FAF-Drugs4, and do not demonstrated predicted hepatotoxicity according ProTox-II.
Lopes, Jo?o Paulo Bizarro,Silva, Luana,da Costa Franarin, Gabriela,Antonio Ceschi, Marco,Seibert Lüdtke, Diogo,Ferreira Dantas, Rafael,de Salles, Cristiane Martins Cardoso,Paes Silva-Jr, Floriano,Roberto Senger, Mario,Alvim Guedes, Isabella,Emmanuel Dardenne, Laurent
p. 5566 - 5577
(2018/10/20)

Synthesis and antimicrobial evaluation of amino sugar-based naphthoquinones and isoquinoline-5,8-diones and their halogenated compounds
Antibiotic resistance has emerged as a serious global public health problem and lately very few antibiotics have been discovered and introduced into clinical practice. Therefore, there is an urgent need for the development of antibacterial compounds with new mechanism of action, especially those capable of evading known resistance mechanisms. In this work two series of glycoconjugate and non-glycoconjugate amino compounds derived from of isoquinoline-5,8-dione and 1,4-naphthoquinone and their halogenated derivatives were synthesized and evaluated for antimicrobial activity against Gram-positive (Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 25923, S. epidermidis ATCC 12228, S. simulans ATCC 27851) and Gram-negative bacteria (E. coli ATCC 25922, Proteus mirabilis ATCC 15290, K. pneumoniae ATCC 4352 and P. aeruginosa ATCC 27853) strains of clinical importance. This study revealed that glycoconjugate compounds derived from halogeno-substituted naphthoquinones were more active against Gram-negative strains, which cause infections whose treatment is even more difficult, according to the literature. These molecules were also more active than isoquinoline-5,8-dione analogues with minimum inhibitory concentration (MIC = 4–32 μg/mL) within Clinical and Laboratory Standard Institute MIC values (CLSI 0.08–256 μg/mL). Interestingly the minimal bactericidal concentration (MBC) values of the most active compounds were equal to MIC classifying them as bactericidal agents against Gram-negative bacteria. Sixteen compounds among eighteen carbohydrate-based naphthoquinones tested showed no hemolytic effects on health human erythrocytes whereas more susceptibility to hemolytic cleavage was observed when using non-glycoconjugate amino compounds. In silico Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) evaluation also pointed out that these compounds are potential for oral administration with low side effects. In general, this study indicated that these compounds should be exploited in the search for a leading substance in a project aimed at obtaining new antimicrobials more effective against Gram-negative bacteria.
Dias, Flaviana R.F.,Novais, Juliana S.,Devillart, Talita A. do Nascimento Santos,da Silva, Wanderson Amaral,Ferreira, Matheus O.,Loureiro, Raquel de S.,Campos, Vinícius R.,Ferreira, Vitor F.,de Souza, Maria C.B.V.,Castro, Helena C.,Cunha, Anna C.
p. 1 - 12
(2018/07/06)

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)

Synthesis of Nucleosides through Direct Glycosylation of Nucleobases with 5-O-Monoprotected or 5-Modified Ribose: Improved Protocol, Scope, and Mechanism
Simplifying access to synthetic nucleosides is of interest due to their widespread use as biochemical or anticancer and antiviral agents. Herein, a direct stereoselective method to access an expansive range of both natural and synthetic nucleosides up to a gram scale, through direct glycosylation of nucleobases with 5-O-tritylribose and other C5-modified ribose derivatives, is discussed in detail. The reaction proceeds through nucleophilic epoxide ring opening of an in situ formed 1,2-anhydrosugar (termed “anhydrose”) under modified Mitsunobu reaction conditions. The scope of the reaction in the synthesis of diverse nucleosides and other 1-substituted riboside derivatives is described. In addition, a mechanistic insight into the formation of this key glycosyl donor intermediate is provided.
Downey, A. Michael,Pohl, Radek,Roithová, Jana,Hocek, Michal
supporting information
p. 3910 - 3917
(2017/03/27)

Method for preparing ticagrelor key intermediate
The invention relates to a chemical synthesis method of ticagrelor key intermediate 2-[[(3aR, 4S, 6R, 6aS)-6-aminotetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxolane-4-yl] oxy]ethanol (a key intermediate A). The method comprises the following steps: taking D-ribose as a raw material, and carrying out ten chemical reaction steps of 1-locus methylation and 2,3-loci isopropylidene protection, 4-locus derivatization, iodination, furan ring-opening, hydroxylamine reaction, palladium on carbon catalytic hydrogenation, amino Cbz protection, hydroxy protection, sodium borohydride reduction ester, Cbz removal protection and the like, thereby obtaining the key intermediate A. The raw materials are cheap and readily available, the preparation process is high in operability, steps of optical resolution, chiral induction and the like are avoided, the total yield is relatively high, and the product quality is better; particularly due to the use of sodium borohydride reduction ester, the preparation cost of ticagrelor is greatly reduced; and the method is suitable for large-scale industrial production.
-
Paragraph 0018; 0041; 0042

(2017/02/17)

N2-glycosyl-substituted 1,2,3-triazole compound and synthesis method and application thereof
The invention relates to an N2-glycosyl-substituted 1,2,3-triazole compound and a synthesis method and application thereof. The general structural formula of the N2-glycosyl-substituted 1,2,3-triazole compound is shown in the specification, wherein R1 indicates H atoms or halogen atoms or alkyl groups of 1-6 carbon atoms or alkoxy groups of 3-10 carbon atoms or aryl groups or heterocyclic groups or benzoyl groups or formyloxy groups or cyano groups, and R indicates hydrogen or alkyl groups or halogen atoms or nitro groups or alkoxy groups or cyano groups and is located at ortho-position, meta-position and para-position single substitution or polysubstitution of aromatic rings. The N2-glycosyl-substituted 1,2,3-triazole compound and the synthesis method and application thereof have the advantages that synthesis conditions are easy to control, the yield is high, and the cost is low; application of triazole derivatives in the fields of pesticide, medicine, food and the like is further promoted; a new way is provided for research and development of high-value utilization and modification of triazole; the compound has high inhibiting ability for alpha-glucosidase and can be further developed into medicine used for treating or assisting in treating diabetes mellitus type 2.
-
(2017/01/26)

Capecitabine and wherein the intermediate preparation method
The invention discloses a preparation method of capecitabine. The method comprises the following steps: based on D-ribose serving as a starting raw material, carrying out hydroxyl protection, 5-site tosylation, iodine substitution, hypophosphorous acid deiodination and acetylation so as to obtain the key intermediate 12,3-tri-O-acetyl-5-deoxy-beta-D-ribofuranose; carrying out glycosylation on the key intermediate and 5-fluorocytosine; and finally, carrying out N-4 site acylation and deprotection so as to obtain the capecitabine. In the method, a metal catalyst dose not need to be used for participating in reaction, the reaction condition is mild, and the yield is high, thus the method is economical and effective as well as suitable for industrial production on a large scale.
-
(2017/02/09)

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, characterization, cytotoxic and antitubercular activities of new gold(I) and gold(III) complexes containing ligands derived from carbohydrates
Novel gold(I) and gold(III) complexes containing derivatives of d-galactose, d-ribose and d-glucono-1,5-lactone as ligands were synthesized and characterized by IR, 1H, and 13C NMR, high resolution mass spectra and cyclic voltammetry. The compounds were evaluated in vitro for their cytotoxicity against three types of tumor cells: cervical carcinoma (HeLa) breast adenocarcinoma (MCF-7) and glioblastoma (MO59J) and one non-tumor cell line: human lung fibroblasts (GM07492A). Their antitubercular activity was evaluated as well expressed as the minimum inhibitory concentration (MIC90) in μg/mL. In general, the gold(I) complexes were more active than gold(III) complexes, for example, the gold(I) complex (1) was about 8.8 times and 7.6 times more cytotoxic than gold(III) complex (8) in MO59J and MCF-7 cells, respectively. Ribose and alkyl phosphine derivative complexes were more active than galactose and aryl phosphine complexes. The presence of a thiazolidine ring did not improve the cytotoxicity. The study of the cytotoxic activity revealed effective antitumor activities for the gold(I) complexes, being more active than cisplatin in all the tested tumor cell lines. Gold(I) compounds (1), (2), (3), (4) and (6) exhibited relevant antitubercular activity even when compared with first line drugs such as rifampicin.
Chaves, Joana Darc Souza,Damasceno, Jaqueline Lopes,Paula, Marcela Cristina Ferreira,De Oliveira, Pollyanna Francielli,Azevedo, Gustavo Chevitarese,Matos, Renato Camargo,Louren?o, Maria Cristina S.,Tavares, Denise Crispim,Silva, Heveline,Fontes, Ana Paula Soares,De Almeida, Mauro Vieira
p. 845 - 860
(2015/09/29)

Synthesis of a new class of naphthoquinone glycoconjugates and evaluation of their potential as antitumoral agents
A novel series of carbohydrate-based naphthoquinones was synthesized and evaluated for cytotoxicity against different cancer cell lines. The compounds derived from 5-hydroxy-1,4-naphthoquinone (juglone) showed better cytotoxicity profiles against HCT-116, A-549 and MDA-MB 435 human cancer cells than the parent compound. The results suggest that the hydroxyl group on the aromatic ring increased the pro-oxidant activity of these new naphthoquinone derivatives. Furthermore, two derivatives were found to be more active against melanoma cells (MDA-MB435) than the clinically useful anticancer agent doxorubicin, and none of the compounds caused mouse erythrocyte lysis.
Campos, Vinicius R.,Cunha, Anna C.,Silva, Wanderson A.,Ferreira, Vitor F.,Santos De Sousa, Carla,Fernandes, Patrícia D.,Moreira, Vinícius N.,Da Rocha, David R.,Dias, Flaviana R. F.,Montenegro, Raquel C.,De Souza, Maria C. B. V.,Boechat, Fernanda Da C. S.,Franco, Caroline F. J.,Resende, Jackson A. L. C.
p. 96222 - 96229
(2015/11/24)

Revisiting synthetic preparation of the quorum sensing substrate S-d-ribosyl-l-homocysteine (SRH)
Cleavage of the thioether bond of S-d-ribosyl-l-homocysteine (SRH) by the enzyme S-ribosylhomocysteinase (LuxS) serves as the final biosynthetic step in the generation of the quorum sensing autoinducer AI-2 by bacteria. Herein, a revised chemical synthesis of SRH is presented at convenient scale and purity for in vitro studies of LuxS. Potassium bis(trimethylsilyl)amide (KHMDS) is identified as a judicious base for the formation of the thioether of the target compound from readily-accessible precursors: a thiol nucleophile derived from l-homocystine and a sulfonate-activated d-ribosyl electrophile. The exclusive use of acid-labile protecting groups allows for facile deprotection to the final product, producing the TFA salt of SRH in five synthetic steps and 26% overall yield. The chemically-synthesized material is isolated at high purity and demonstrated to serve as the LuxS substrate by an in vitro assay.
Bolitho, Megan E.,Corcoran, Brendan J.,Showell-Rouse, Emily I.,Wang, Keeshia Q.
p. 32 - 38
(2014/07/08)

Click chemistry inspired highly facile synthesis of triazolyl ethisterone glycoconjugates
Numerous deoxy-azido sugars 3 were prepared by the reaction of tosyl/bromo sugars with NaN3 in dry DMF under heating condition. The 1,3-dipolar cycloaddition of deoxy-azido sugars 3 with ethisterone 4 to afford regioselective triazole-linked ethisterone glycoconjugates 5 was investigated in the presence of CuI and DIPEA in dichloromethane or CuSO4· 5H2O and sodium ascorbate in aqueous medium. All the developed compounds were characterized by spectroscopic analysis (IR, 1H & 13C NMR, and MS spectra). Structure of triazolyl ethisterone glycoconjugate 5a has been further confirmed by its Single Crystal X-ray analysis.
Kumar, Dhananjay,Mishra, Kunj B.,Mishra, Bhuwan B.,Mondal, Saheli,Tiwari, Vinod K.
supporting information
p. 71 - 79
(2014/01/17)

Structure-activity relationship of adenosine 5′-diphosphoribose at the transient receptor potential melastatin 2 (TRPM2) channel: Rational design of antagonists
Adenosine 5′-diphosphoribose (ADPR) activates TRPM2, a Ca 2+, Na+, and K+ permeable cation channel. Activation is induced by ADPR binding to the cytosolic C-terminal NudT9-homology domain. To generate the first structure-activity relationship, systematically modified ADPR analogues were designed, synthesized, and evaluated as antagonists using patch-clamp experiments in HEK293 cells overexpressing human TRPM2. Compounds with a purine C8 substituent show antagonist activity, and an 8-phenyl substitution (8-Ph-ADPR, 5) is very effective. Modification of the terminal ribose results in a weak antagonist, whereas its removal abolishes activity. An antagonist based upon a hybrid structure, 8-phenyl-2′-deoxy-ADPR (86, IC50 = 3 μM), is more potent than 8-Ph-ADPR (5). Initial bioisosteric replacement of the pyrophosphate linkage abolishes activity, but replacement of the pyrophosphate and the terminal ribose by a sulfamate-based group leads to a weak antagonist, a lead to more drug-like analogues. 8-Ph-ADPR (5) inhibits Ca2+ signalling and chemotaxis in human neutrophils, illustrating the potential for pharmacological intervention at TRPM2.
Moreau, Christelle,Kirchberger, Tanja,Swarbrick, Joanna M.,Bartlett, Stephen J.,Fliegert, Ralf,Yorgan, Timur,Bauche, Andreas,Harneit, Angelika,Guse, Andreas H.,Potter, Barry V. L.
p. 10079 - 10102
(2014/01/17)

SYNTHESIS OF TRIAZOLOPYRIMIDINE COMPOUNDS
The present invention relates to the field of organic synthesis and describes the synthesis of specific intermediates suitable for the preparation of triazolopyrimidine compounds such as ticagrelor.
-
(2013/07/05)

Synthesis of Aminocyclopentanetriol Derivatives
The present invention relates to the field of organic synthesis and describes the synthesis of specific intermediates suitable for the preparation of triazolopyrimidine compounds such as ticagrelor. The present invention provides in particular a process for the preparation of a compound of formula V comprising: a) providing a compound of formula IV , and b) reducing the compound of formula IV with activated zinc in the presence of copper to give the compound of formula V.
-
(2014/01/07)

Synthesis and biological evaluation of ticagrelor derivatives as novel antiplatelet agents
Ticagrelor (1) is the first reversible P2Y12 receptor antagonist blocking adenine diphosphate (ADP)-induced platelet aggregation with rapid onset and offset of effects. In this study, synthesis of ticagrelor and its derivatives has been accomplished in a convergent way. The compound design was based on modifications of ticagrelor and its major metabolite (33) in order to ameliorate their pharmacokinetic properties and dosing profile. The final compounds (1a-g, 35a-g) were evaluated for their inhibitory effect on ADP-induced platelet aggregation in rats. The assay results showed that some compounds (e.g., 1b, 1d, 33, 35b, 35f) exhibited comparable potency with that of ticagrelor.
Zhang, Hao,Liu, Jun,Zhang, Luyong,Kong, Lingyi,Yao, Hequan,Sun, Hongbin
p. 3598 - 3602
(2012/07/14)

Synthesis, Biological Activity, and Molecular Modeling Studies of 1H-1,2,3-Triazole Derivatives of Carbohydrates as a-Glucosidases Inhibitors
A class of drugs in use for treating type II diabetes mellitus (T2D), typified by the pseudotetrasaccharide acarbose, act by inhibiting the a-glucosidase activity present in pancreatic secretions and in the brush border of the small intestine. Herein, we report the synthesis of a series of 4-substituted 1,2,3-triazoles conjugated with sugars, including D-xylose, D-galactose, D-allose, and D-ribose. Compounds were screened for a-glucosidase inhibitory activity using yeast maltase (MAL12) as a model enzyme. Methyl2,3-O-isopropylidene-β-D-ribofuranosides, such as the 4-(l-cyclohexenyl)-l,2,3-triazole derivative, were among the most active compounds, showing up to 25-fold higher inhibitory potency than the complex oligosaccharide acarbose. Docking studies on a MAL12 homology model disclosed a binding mode consistent with a transition-state-mimicking mechanism. Finally, the actual pharmacological potential of this triazole series was demonstrated by the reduction of postprandial blood glucose levels in normal rats. These compounds could represent new chemical scaffolds for developing novel drugs against T2D.
Ferreira, Sabrinab,Sodero, Ana C. R.,Cardoso, Mariana F. C.,Lima, Emerson S.,Kaiser, Carlos R.,Silva Jr., Floriano P.,Ferreira, Vitor F.
supporting information; experimental part
p. 2364 - 2375
(2010/09/04)

METHOD FOR THE PREPARATION OF CAPECITABINE AND INTERMEDIATES USED IN SAID METHOD
A process to obtain capecitabine compound and its pharmaceutically acceptable derivatives is hereby disclosed. Likewise, novel intermediates to be used in the preparation of capecitabine compound and its pharmaceutically acceptable derivatives are also disclosed. The procedure comprises the stage of causing a reaction of N4-(n-pentyloxycarbonyl))-5- fluorocytosine with (1,2,3-tri-O-acetyl-5-deoxy- α,β-D-ribofuranose.
-
Page/Page column 8

(2010/11/03)

HYDROXAMIC ACID DERIVATIVES
The disclosure includes hydroxamic compounds of Formula I: (I) wherein P, Z, and m are defined herein. Also disclosed is a method for treating a neoplastic disease or an immune disease with these compounds.
-
(2010/08/08)

PREPARATION OF CAPECITABINE
The present invention relates to substantially pure capecitabine and processes for the preparation thereof.
-
Page/Page column 22

(2010/06/20)

Total synthesis of aigialomycin D using a Ramberg - Baecklund/ RCM strategy
The bioactive resorcylic acid lactone aigialomycin D (1) has been synthesized by a novel combination of ring-closing metathesis (RCM) and Ramberg - Baecklund reactions. This synthetic strategy enables the Cl - C2 alkene to be masked as a sulfone during formation of the macrocycle by ring closing metathesis at the C7 - C8 olefin, thus avoiding competing formation of a cyclohexene. A subsequent Ramberg-Baecklund reaction efficiently produces the C1- C2 E-alkene. This combined RCM/ Ramberg-Baecklund reaction strategy should be widely applicable to the synthesis of maerocyclic dienes.
Baird, Lynton J.,Timmer, Mattie S. M.,Teesdale-Spittle, Paul H.,Harvey, Joanne E.
supporting information; experimental part
p. 2271 - 2277
(2009/08/07)

Reaction of methyl-4-methylene-2,3-O-isopropylidene-β-D-ribofuranoside with N-bromosuccinimide in aqueous tetrahydrofurane
Methyl-4-methylene-2,3-O-isopropylidene-β-D-ribofuranoside prepared from D-ribose reacted in a system NBS-THF-H2O to give a mixture of stereoisomeric products of regioselective bromohydroxylation of a double bond. The reaction involved a hydrolysis of the glycoside bond, but the acetonide protective group was retained. The mechanism of the selective hydrolysis originating from the ring-chain tautomerism of bromohydrins obtained was proved by the 1H NMR spectra of the steroisomeric methyl-5-deoxy-5-bromo-4- hydroxy-2,3-O-isopropylidene-β-D-ribofuranosides. By crotonic cyclization of the formed masked 1,4-dicarbonyl compounds at heating in benzene in the presence of neutral Al2O3 a new chiral cyclopentenone block, 2-bromo-4,5-isopropylideneoxycyclopent-2-en-1-one, was obtained in a low yield. Nauka/Interperiodica 2007.
Ivanova,Valiullina,Shitikova,Miftakhov
p. 742 - 746
(2008/02/08)

Synthesis and Anti-HBV Activity of Thiouracils Linked via S and N-1 to the 5-Position of Methyl β-D-Ribofuranoside
Reverse nucleoside derivatives of 2-(methylsulfanyl)uracils 6a-d were prepared by treating of the sodium salt of 2-(methylsulfanyl)uracils (5a-d) with methyl 2,3-O-isopropylidene-5-O-p-toluenesulfonyl-β-D-ribofuranoside (2). The alkylation of 2-thiouracils 4a-d with methyl 5-deoxy-5-iodo-2,3-O-isopropylidene-D-ribofuranoside (3) afforded the corresponding S-ribofuranoside derivatives 8a-d. Deisopropylidenation of 6a-d and 8a-d afforded the corresponding deprotected derivatives 7a-d and 9a-d, respectively. The Anti-HBV activity of selected compounds was studied.
Abdel-Rahman, Adel A.-H.,Abdel-Megied, Ahmed E.-S.,Goda, Adel E.-S.,Zeid, Ibrahim F.,El Ashry, El Sayed H.
p. 2027 - 2038
(2007/10/03)

Synthesis of 1,2,3-tri-O-acetyl-5-deoxy-D-ribofuranose from D-ribose
A practical route towards the synthesis of 1,2,3-tri-O-acetyl-5-deoxy-D-ribofuranose from D-ribose is described. The key steps include deoxygenation of methyl 2,3-O-isopropylidene-5-O-sulfonyloxy-β-D-ribofuranoside by reductive displacement employing hydride reagents. Subsequent total hydrolysis followed by acetylation led to the title compound in 56% overall yield from D-ribose. The sequence is simple, inexpensive, high yielding and clearly suitable for multi-gram preparations.
Sairam, Pothukuchi,Puranik, Ramachandra,Sreenivasa Rao, Bhatraju,Veerabhadra Swamy, Ponnapalli,Chandra, Sharad
p. 303 - 306
(2007/10/03)

An improved synthesis of (R)-2,3-dihydroxypropyl 5-deoxy-5-dimethylarsinyl-β-D-riboside, a common marine arsenical
An efficient synthesis of (R)-2,3-dihydroxypropyl 5-deoxy-5-dimethylarsinyl-β-D-riboside, a common marine arsenical, from D-ribose, (S)-2,3-dibenzyloxypropanol and iododimethylarsine is described.
Stick,Stubbs,Tilbrook
p. 181 - 183
(2007/10/03)

Synthesis and cytokine modulation properties of pyrrolo[2,3.d]-4- pyrimidone nucleosides
A series of pyrrolo[2,3-d]pyrimidone nucleosides were synthesized and evaluated for their ability to enhance Type 2 cytokines and to suppress Type 1 cytokines in human T cells activated in vitro. Compounds 16b, 16c, 16d, 18c, and 19b induced substantial enhancement of IL-4 (a Type 2 cytokine) levels while three compounds (16b, 16c, and 16f) showed significant suppression of IFNγ (a Type 1 cytokine) levels. The results revealed a strict structural requirement for the nucleoside-mediated enhancement of IL- 4. Modifications of the ribofuranose moiety of the nucleosides either abolished or dramatically reduced the activity. Both the 5'-hydroxy and 5- carboxamidine are crucial for the activity. Of the few nucleoside analogues that demonstrated enhancement on Type 2 cytokine production, 7-(β-D- ribofuranosyl)pyrrolo[2,3d]-4-pyrimidone-5-carboxamidine (16c) showed a dramatic enhancement (> 200%) of IL-4 levels and a significant enhancement (36%) of IL-5 levels. Moreover, this compound showed substantial suppression of the Type 1 cytokines, IFNγ (42%), IL-2 (54%), and TNFα (55%). Similarly, compound 16b showed a substantial enhancement of IL-4 (46%) and suppression of IL-2 (35%), IFNγ (30%), and TNFα (26%). To our knowledge, these are the first nucleoside analogues that induce a Type 2 cytokine bias in T cells. The cytokine modulation property of 16c and 16b merits the therapeutic evaluation of these compounds in treating diseases in which immunopathology is associated with polarized Type 1 cytokine responses.
Wang, Guangyi,Tam, Robert C.,Gunic, Esmir,Du, Jinfa,Bard, Josie,Pai, Bharati
p. 2566 - 2574
(2007/10/03)

Studies on the synthesis of tunicamycin. The preparation of 7-deoxy-2-deamino-6-hydroxy tunicamine and related products
The condensation of methyl 5-deoxy-5-diazo-2,3-O-isopropylidene-β-D-ribofuranoside with 1,2:3,4-di-O-isopropylidene-D-galactohexonodialdo-1,5-pyranoside gave the ketone C-disaccharide 11 as the sole product. This ketone was transformed into different derivatives. Thus, its reduction led stereoselectively to the corresponding alcohols. Similar transformations led to the corresponding alkane and amino derivatives, of potential biological interest as inhibitors for glycosidases. These results can be useful for the synthesis of tunicamine and its analogues.
Sarabia-Garcia, Francisco,Lopez-Herrera, F. Jorge
p. 4757 - 4768
(2007/10/03)

SYNTHESIS AND N.M.R.-SPECTRAL ANALYSIS OF UNENRICHED AND -ENRICHED 5-DEOXYPENTOSES AND 5-O-METHYLPENTOSES
Chemical methods are described for preparing unenriched and -enriched 5-deoxy- and 5-O-methyl-pentoses in the D or L configuration.The 1H-n.m.r.-spectra of these compounds have been interpreted, and the 13C n.m.r. spectra assigned with the aid of 2-D 13C-1H chemical-shift correlation spectroscopy.Tautomeric forms (furanoses, hydrate, and aldehyde) in solution in 2H2O have been quantified with the aid of -enriched derivatives.Spectra of 5-deoxypentoses, and methyl pentofuranosides have been compared, in order to assess the effect of 5-C-deoxygenation and 5-O-methylation on chemical shifts and coupling constants (1H-1H, 13C-1H, and 13C-13C) and on the pentofuranose conformations.
Snyder. Joseph R.,Serianni, Anthony S.
p. 169 - 188
(2007/10/02)