- Synthesis and in vitro antitumour activity of 4(R)-methyl-3-O-phosphonomethyl-α-L-threose nucleosides
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A series of novel α-L-threose nucleoside phosphonate analogs, 4(R)-methyl-3-O-phosphonomethyl-α-L-threose nucleosides, were synthesized in multistep sequences starting from D-xylose. The synthetic sequence consisted of the following key stages: (i) the multistep synthesis of 1,2-O-isopropylidenyl-4(R)-methyl-3-O-phosphonomethyl-L-threose, (ii) the transformation of 1,2-O-isopropylidenyl sugar into suitable 1,2-di-O-acyl L-threose precursor, and (iii) the construction of target α-L-threose nucleoside phosphonate analogs by Vorbrüggen glycosidation reaction, deprotection of acyl group, and hydrolysis of diethyl group on phosphonate. The target nucleoside phosphonates were evaluated for their antitumour activities in cell culture-based assays. Compound 8g, 2-fluroadenosine phosphonate, showed remarkable activity against human breast cancer cell lines (MCF-7 and MDA-MB-231) with IC50 values of 0.476 and 0.391 μM, corresponding to 41- and 47-fold higher potency than the reference compound 5-FU, respectively. Subsequent investigations found that the compound 8g can inhibit the proliferation of breast cancer cells and cell cloning. The mechanistic studies indicated that compound 8g could cause DNA damage to breast cancer cells through the ATM-Chk1/Chk2-cdc25c pathway, leading to blockage of the G2/M phase cycle of breast cancer cells, which ultimately led to apoptosis. Moreover, 8g could inhibit the PI3K/AKT signaling pathway and induce apoptosis. These results indicate that compound 8g holds promising potential as an antitumour agent.
- Liu, Feng-Wu,Ji, Shujie,Gao, Yingying,Meng, Yao,Xu, Wenke,Wang, Haixia,Yang, Jing,Huang, Hao,Herdewijn, Piet,Wang, Cong
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- Synthesis and Antiviral Evaluation of 3'-C-Hydroxymethyl-3'-O-Phosphonomethyl-β-D-5'-deoxyxylose Nucleosides
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L-2'-deoxythreose nucleoside phosphonates PMDTA and PMDTT possess potent anti-HIV activity. Herein, a novel class of 3'-C-branched-l-threose nucleoside phosphonate analogs, 5'-deoxy-3'-C-hydroxymethyl-3'-O-phosphonomethyl-d-xylose nucleosides, were synthesized and biologically evaluated. The key sugar intermediate 3-C-benzyloxymethyl-3-O-diethylphosphonomethyl-1,2-O-isopropylidene-α-d-5-deoxyxylose (8) was firstly synthesized, which may be an interesting scaffold for access to diverse 3'-C-branched l-threosyl nucleoside phosphonate derivatives. And the key synthesis involved Wittig olefination of 1,2-O-isopropylidene-3-oxo-α-d-5-deoxyxylose, stereoselective dihydroxylation of alkenes by aqueous KMnO4, selective benzylation of hydroxymethyl group under activation of dibutyltin oxide, and introduction of phosphonate group by nucleophilic substitution. Eventually, glycosylation under Vorbrüggen conditions provided 3'-C-hydroxymethyl-3'-O-phosphonomethyl-β-d-5'-deoxyxylose nucleoside analogs in satisfying yield.
- Gao, Yingying,Herdewijn, Piet,Huo, Xiangyu,Ji, Shujie,Liu, Feng-Wu,Wang, Haixia,Wang, Song,Xu, Wenke
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- Antitumor (4' R)-methyl - α-L . (by machine translation)
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The invention discloses novel α-L - fucosa nucleoside phosphonate analogs, and particularly relates to (4 ′). R- Methyl -3 ' - methyl phosphonic acid - α-L . It has the structure shown in Formula 1. Wherein R ' represents H, Na, K or NH. 4 Ions; B stands for uracil, thymine, 5 - chlorouracil, 5 - fluorouracil, 5 -bromouracil, 5 -fluorouracil, cytosine, 5 - fluorocytosine, adenine, 2 - fluoroadenine, 2 - chloroadenine, 2 - aminoadenine and guanine. The compound has anti-tumor activity and good development prospect. (by machine translation)
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Paragraph 0050; 0053
(2020/06/09)
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- Palladium-catalyzed enantioselective allylic substitution in the presence of monodentate furanoside phosphoramidites
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A library of monodentate furanoside phosphoramidites, easily synthesized from inexpensive D-xylose and optically pure 1,1-bi-2-naphthol (BINOL), was used as ligands for the palladium-catalyzed allylic alkylation and amination. The matched pair was formed from D-xylose-derivatives and (S)-BINOL. The asymmetric induction depends strongly on the substituent at the C5 of the carbohydrate backbone; both bulky 5-O-pivaloyl and 5-deoxy derivatives gave excellent results, whereas ligands with trityl protection at position C5 induced low ee values with reversal of configuration. The solvent used for the addition is also of great importance with highest enantioselectivities observed in diethyl ether. The best results for both alkylation and amination, up to 98-99 ee, were obtained for sterically demanding allylic acetates. Single is better: New carbohydrate ligands bearing a single 1,1-bi-2-naphthol (BINOL)-derived phosphoramidite moiety are developed and successfully applied to the palladium-catalyzed asymmetric allylic substitution. The enantioselectivities are equal or better than those obtained for similar systems containing two BINOL moieties and reach up to 99 ee.
- Majdecki, Maciej,Jurczak, Janusz,Bauer, Tomasz
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p. 799 - 807
(2015/03/14)
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- Generation of a low-valent titanium species from titanatrane and its catalytic reactions: Radical ring opening of oxetanes
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Treatment of a titanatrane complex with trimethylsilyl chloride and magnesium powder in tetrahydrofuran generated a low-valent titanium species. This species catalyzed the radical ring opening of epoxides and oxetanes to produce the corresponding less substituted alcohols. The reagent also catalyzed the deallylation and depropargylation of allylic and propargylic ethers, respectively, to provide the parent alcohols.
- Takekoshi, Naoto,Miyashita, Kenji,Shoji, Noriaki,Okamoto, Sentaro
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supporting information
p. 2151 - 2157
(2013/10/01)
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- Batch to flow deoxygenation using visible light photoredox catalysis
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Herein we report a one-pot deoxygenation protocol for primary and secondary alcohols developed via the combination of the Garegg-Samuelsson reaction, visible light-photoredox catalysis, and flow chemistry. This procedure is characterized by mild reaction conditions, easy-to-handle reactants and reagents, excellent functional group tolerance, and good yields.
- Nguyen, John D.,Reiss, Barbara,Dai, Chunhui,Stephenson, Corey R. J.
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supporting information
p. 4352 - 4354
(2013/06/05)
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- First total synthesis of a naturally occurring iodinated 5′-deoxyxylofuranosyl marine nucleoside
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4-Amino-7-(5′-deoxy-β-D-xylofuranosyl)-5-iodo-pyrrolo[2,3-d] pyrimidine 1, an unusual naturally occurring marine nucleoside isolated from an ascidan, Diplosoma sp., was synthesized from D-xylose in seven steps with 28% overall yield on 10 g scale. The key step was Vorbrueggen glycosylation of 5-iodo-pyrrolo[2,3-d]pyrimidine with 5-deoxy-1, 2-O-diacetyl-3-O-benzoyl-D- xylofuranose. Its absolute configuration was confirmed.
- Sun, Jianyun,Dou, Yanhui,Ding, Haixin,Yang, Ruchun,Sun, Qi,Xiao, Qiang
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experimental part
p. 881 - 889
(2012/07/14)
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- Engaging unactivated alkyl, alkenyl and aryl iodides in visible-light-mediated free radical reactions
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Radical reactions are a powerful class of chemical transformations. However, the formation of radical species to initiate these reactions has often required the use of stoichiometric amounts of toxic reagents, such as tributyltin hydride. Recently, the use of visible-light-mediated photoredox catalysis to generate radical species has become popular, but the scope of these radical precursors has been limited. Here, we describe the identification of reaction conditions under which photocatalysts such as fac-Ir(ppy) 3 can be utilized to form radicals from unactivated alkyl, alkenyl and aryl iodides. The generated radicals undergo reduction via hydrogen atom abstraction or reductive cyclization. The reaction protocol utilizes only inexpensive reagents, occurs under mild reaction conditions, and shows exceptional functional group tolerance. Reaction efficiency is maintained upon scale-up and decreased catalyst loading, and the reaction time can be significantly shortened when the reaction is performed in a flow reactor.
- Nguyen, John D.,D'Amato, Erica M.,Narayanam, Jagan M. R.,Stephenson, Corey R. J.
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p. 854 - 859
(2012/11/07)
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- NOVEL DERIVATIVES OF ACYL CYANOPYRROLIDINES
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A compound of formula (I) or a tautomeric form, regioisomer, stereoisomer, solvate, N-oxide or pharmaceutically acceptable salts thereof; wherein 'a' - is selected from the group consisting of substituted or unsubstituted heterocycloalkyl ring and substituted or unsubstituted carbohydrate moiety y is a member selected from -O-, -CO-, -S02-, aminoalkyl or formula (II) wherein, Rw is hydrogen, substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl; x is a member selected from -0-, -S-, -SO-, -S02-, CONR10, NR10CO and -NRd-, or x and y together represent a chemical bond; Z is selected from -CH-, -N-. t is an integer selected from O to 4; with the provisos that when 'a' is substituted or unsubstituted heterocycloalkyl ring then 't' is not O and when y = -CO-, x is not NRd.
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Page/Page column 144-145
(2009/10/22)
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- Processes for the preparation of (R)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol"
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The present invention provides various processes for the preparation of (R)-±-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol. These processes may be characterized by the following scheme:
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Page/Page column 49
(2010/11/25)
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- Facile Barton-McCombie deoxygenation of alcohols with tetrabutylammonium peroxydisulfate and formate ion
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(Chemical Equation Presented) A new method for efficient radical deoxygenation of alcohols is described for preparing bulk chemicals avoiding scale-up problems. Treatment of various thiocarbonyl derivatives with (Bu 4N)2S2O8 and HCO2Na in DMF afforded the corresponding deoxygenated products in excellent yields. The deoxygenation appears to be initiated by the transfer of a single electron to thiocarbonyl derivatives from CO2?- rather than from SO4?-.
- Hee, Sock Park,Hee, Yoon Lee,Yong, Hae Kim
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p. 3187 - 3190
(2007/10/03)
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- Binding and catalysis by yeast aldose reductase: A substrate-analog approach with new aldose derivatives
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5-Deoxy-D-xylofuranose derivatives and a range of new 5,6-dideoxy analogs of D-glucofuranose bearing azido or fluoro substituents were synthesised and employed as substrates of the NADH-dependent aldehyde reduction catalysed by yeast aldose reductase. In
- Hadwiger, Philipp,Mayr, Peter,Tauss, Andreas,Stuetz, Arnold E.,Nidetzky, Bernd
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p. 1683 - 1686
(2007/10/03)
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- Convenient catalytic free radical reductions of alkyl halides using an organotin reagent on non-cross-linked polystyrene support
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(matrix presented) A highly efficient and catalytic organotin reagent on soluble support has been developed for free radical reactions. The non-cross-linked polystyrene copolymer support allows solubility in most organic solvents such as CHCl3, benzene, THF, dimethylacetamide (DMA), DMF, and EtOAc; however, the tin reagent can be readily obtained as a white powder from cold methanol. A variety of alkyl halides (1°, 2°, 3°, aryl) underwent radical reductions in good isolated yields (60-93%) using only 0.01-0.2 equiv of the polymer catalyst.
- Enholm, Eric J.,Schulte II, James P.
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p. 1275 - 1277
(2008/02/09)
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- A mild and versatile method for the tetrahydropyranylation of alcohols and their detetrahydropyranylation
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An efficient and mild method for tetrahydropyranylation of alcohols and their detetrahydropranylation using NH4Cl is described. This protocol provides a useful alternative tetrahydropyranylation of alcohols and their deprotection at different pH.
- Yadav,Srinivas, Dale,Reddy, Gondi Sudershan
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p. 1399 - 1404
(2007/10/03)
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- Methyl 5-deoxy-α and β-D-xylofuranosides
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Synthesized from D-xylose, methyl 5-deoxy-α-D-xylofuranoside (1) and methyl 5-deoxy-β-D-xylofuranoside (2) were obtained in overall yields of 24 and 26 %, respectively. The key step in the synthesis was the separation of an anomeric mixture on a strong an
- Moravcova, Jitka,Capkova, Jindra,Stanek, Jan,Raich, Ivan
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p. 1061 - 1073
(2007/10/03)
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- Studies directed towards the synthesis of clonostachydiol - Part I
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A strategy was developed for the first total synthesis of clonostachydiol which inturn would assign the absolute configuration, based on the chiron approach, using carbohydrate derived chiral synthons.This study however culminated in the synthesis of (2R,
- Rao, A. V. Rama,Murthy, V. S.,Sharma, G. V. M.
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p. 139 - 142
(2007/10/02)
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- Synthesis of optically active O-protected (S)- and (R)-3-hydroxyaldehydes
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(S)-3-Formyloxyaldehydes, chiral synthons for natural product synthesis were synthesized via highly stereoselective hydrogenation of the unsaturated furanose ring system derived from D-glucose or D-xylose. Alternatively, (R)-3-formyloxyaldehydes were prepared via deoxygenation of 3-hydroxyfuranoses derived from D-glucose or D-xylose.
- Kang, Suk-Ku,Cho, Hyun-Sung
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p. 367 - 370
(2007/10/02)
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- Practical synthesis of optically pure 3,4-epoxy-5-methyldihydro-2(3H)-furanones from D-xylose by regio- and stereo-selective functionalization
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The known 1,2-O-isopropylidene-5-O-p-tolylsulfonyl-α-D-xylofuranose was converted into its 3-p-nitrobenzoate (13a) and 3-methanesulfonate (13b). (-)-(3S,4S,5R)-3,4-Epoxy-5-methyldihydro-2(3H)-furanone was synthesized from 13a in 5 steps by convers
- Hildebrandt, Bernhard,Nakamura, Yoshikazu,Ogawa, Seiichiro
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- A Concise And General Entry into (R)-4-Hydroxy-2-Substituted Cyclopent-2-enones from D-Glucose: Chiral Intermediates for the Synthesis of PGE2, (-)-Pentenomycin I, and Allethrin
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A general strategy for the transformation of D-glucose into different (R)-4-hydroxycyclopent-2-enones is described.This has been illustrated by the synthesis of (R)-2--4-hydroxycyclopent-2-enone, (R)-2-benzyloxymethyl-4-hydroxycyclopent-2-enone, and (R)-2-allyl-4-hydroxycyclopent-2-enone, which are potential chiral synthons for prostaglandin E2, the antibiotic (-)-pentenomycin I, and the synthetic insecticide allethrin, respectively.The second chiral synthon was obtained by two different routes, one of them involving a novel palladium(0)-catalysed rearrangement of a vinyloxirane intermediate.
- Achab, Said,Das, Bhupesh C.
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p. 2863 - 2873
(2007/10/02)
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- SYNTHESIS AND N.M.R.-SPECTRAL ANALYSIS OF UNENRICHED AND -ENRICHED 5-DEOXYPENTOSES AND 5-O-METHYLPENTOSES
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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.
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p. 169 - 188
(2007/10/02)
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