- Synthesis and Characterization of π-Stacked Phenothiazine-Labeled Oligodeoxynucleotides
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(Matrix Presented) A facile procedure for the incorporation of N-methyl phenothiazine as the terminal nucleoside in oligodeoxynucleotides is reported. The phenothiazine nucleoside analogue is synthesized and then incorporated into DNA using an automated DNA solid-phase synthesizer. Phenothiazine-labeled oligodeoxynucleotides form stable B-form duplexes with higher melting temperatures compared to unlabeled DNA duplexes.
- Hashmi, S. A. Nadeem,Hu, Xi,Immoos, Chad E.,Lee, Stephen J.,Grinstaff, Mark W.
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- 4'-Thionucleosides via in situ pyranose-furanose rearrangements: A short synthesis of the antiherpes agent 2'-deoxy-5-ethyl-4'-thiouridine via direct coupling of a silylated pyrimidine base with a 4-thiopyranose sugar
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Methyl 2-deoxy-3,4-O-thiocarbonyl-β-D-ribopyranoside was converted into the thione carbonate by reaction with thiophosgene. Bromide ion-catalyzed O-S rearrangement produced methyl 2-deoxy-3-O,4-S-carbonyl-4-thio-β-D- ribopyranoside (3a) and the 3-O,4-S isomer 3b. The carbonates were cleaved with ammonia and the 3-O,4-S pyranoside sugar coupled with bis(trimethylsilyl)-5-ethyluracil using trimethylsilyl triflate to provide the antiherpes agenet 2'-deoxy-5-ethyl-4'-thiouridine 9. The reaction proceeded via in situ pyranoside rearrangement of the sugar and subsequent coupling. The pyranoside sugar could also be converted to the furanoside form with Dowes H+ acid resin and coupled in conventional fashion to give the nucleoside. Coupling of methyl 4-O-carbamoyl-2-deoxy-3-thio-β-D- ribopyranoside (4b) with the bis(trimethylsilyl)-5-ethyluracil gave 1-[2-[2- (hydroxymethyl)thiiran-1-yl]-1-methoxyethyl]-5-ethyluracil.
- Jandu,Selwood
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Read Online
- Improved Syntheses of Halofuranose Derivatives with the Desired α-Configuration
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Chlorination of ribofuranose or 2-deoxyribofuranose derivatives was carried out in a 1,4-dioxane solution of hydrogen chloride. This improved procedure allowed the syntheses of 1-chloro-α-D-ribofuranose and 1-chloro-2-deoxy-α-D-ribofuranose derivatives and offered ease of handling, high yield, and the stereo-controlled α-configuration at C-1.
- Chin, Tsung-Mei,Huang, Liang-Kuen,Kan, Lou-Sing
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- A nucleobase analogue that pairs strongly with adenine
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Shaping up for an A: Adenine is the only canonical nucleobase that does not offer a third hydrogen-bonding functionality at its Watson-Crick face, making it difficult to bind with high affinity. A 6-ethynyl-2-pyridone binds more tightly and with greater sequence fidelity than thymine. VdW=van der Waals interactions. Copyright
- Minuth, Marco,Richert, Clemens
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- Regioselective and stereoselective route to N2-β-tetrazolyl unnatural nucleosides via SN2 reaction at the anomeric center of Hoffer's chlorosugar
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We are reporting a regioselective and stereoselective route to N2-β-tetrazolyl aromatic donor/acceptor unnatural nucleosides as new class of possible DNA base analogs. The SN2 substitution reaction at the anomeric center of Hoffer's chlorosugar with various 5-substituted aromatic tetrazoles in THF in presence of K2CO3 proceeds with regioselectivity at N2-tetrazoles and stereoselectivity at α-chlorosugar with very good yield. The stereoelectronic and steric effects play a crucial role for the observed outcome which is also supported from a theoretical (DFT) study. The methodology is simple, eco-compatible and the tetrazolyl unnatural nucleosides might find applications in decorating DNA for various biotechnological and DNA based material science applications.
- Bag, Subhendu Sekhar,Talukdar, Sangita,Anjali
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- 2-deoxy-D-ribose derivative
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The invention belongs to the field of medicine synthesis, and provides a 2-deoxy-D-ribose derivative (III). When the derivative (III) is used for preparing decitabine, the stereoselectivity is good, and the yield is high. The invention provides a preparation method of the derivative. The preparation method comprises the following steps: step a, carrying out oxygen methylation on 1-position hydroxyl of 2-deoxy-D-ribose; and step b, protecting hydroxyl groups at positions 3 and 5, and further carrying out sulfonation on 1-position oxymethyl. The method is simple and convenient to operate, free of special equipment, good in product purity, high in yield and suitable for industrial production.
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Paragraph 0048-0050; 0055-0057
(2020/08/09)
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- Purification method of decitabine intermediate
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The invention belongs to the technical field of medicinal chemistry, and particularly relates to a purification method of a decitabine intermediate. The method comprises the following steps: dissolving a decitabine intermediate crude product in a first solvent such as trichloromethane, and adding a second solvent such as methyl tert-butyl ether, so that impurities generated in the synthesis process can be effectively removed, and the proportion of beta-configuration products can be increased when the refined intermediate is subjected to a glycosylation reaction.
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Paragraph 0038; 0039
(2020/07/24)
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- The development of β-selective glycosylation reactions with benzyl substituted 2-deoxy-1,4-dithio-D-erythro-pentofuranosides: enabling practical multi-gram syntheses of 4'-Thio-2'-deoxycytidine (T-dCyd) and 5-aza-4’-thio-2’-deoxycytidine (aza-T-dCyd) to s
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The lack of effective methods to perform direct β-selective glycosylation reactions with 2-deoxy-1,4-dithio-D-erythro-pentofuranosides has long been a significant stumbling block for the multi-gram synthesis of 4’-thio-2’-deoxy nucleosides. In addition, p
- Wishka, Donn G.,Lopez, Omar D.,Rudchenko, Vladimir F.,Huang, Guangfei,Bahde, Robert,Kumar, Vineet,Denysenko, Sergiy M.,Zhang, Lianhao,Zhang, Mianji,Teicher, Beverly A.,Morris, Joel
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- Iron-Catalyzed Radical Cleavage/C?C Bond Formation of Acetal-Derived Alkylsilyl Peroxides
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A novel radical-based approach for the iron-catalyzed selective cleavage of acetal-derived alkylsilyl peroxides, followed by the formation of a carbon–carbon bond is reported. The reaction proceeds under mild reaction conditions and exhibits a broad substrate scope with respect to the acetal moiety and the carbon electrophile. Mechanistic studies suggest that the present reaction proceeds through a free-radical process involving carbon radicals generated by the homolytic cleavage of a carbon–carbon bond within the acetal moiety. A synthetic application of this method to sugar-derived alkylsilyl peroxides is also described.
- Shiozaki, Yoko,Sakurai, Shunya,Sakamoto, Ryu,Matsumoto, Akira,Maruoka, Keiji
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supporting information
p. 573 - 576
(2020/02/20)
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- Synthesis method of desicitabine intermediate alpha-substituted deoxyribose
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The invention provides a synthesis method of desicitabine intermediate alpha-substituted deoxyribose. The synthesis route is as follows: R refers to p-methyl benzoyl and X refers to chlorine atomin according to the formula 3 and the formula I. The synthesis method includes the following steps: 1) methylation reaction: a compound of formula 1 is reacted with methyl alcohol under acid catalysis to obtain a compound of the formula 2; 2) acylation reaction: the compound of the formula 2 is dissolved in an organic solvent and reacted with p-methyl benzoyl chloride under alkali catalysis to obtain acompound of the formula 3; 3) chlorination reaction: acetyl chloride is used to adjust the pH value of the acylation reaction solution at low temperature, the acylation reaction solution is filtered,is added with a low polar solvent A, and then is added with acetic acid solution of hydrogen chloride to react to obtain a compound of formula I. The synthesis method uses p-methyl benzoyl as a protective group in the process of synthesizing dicitabine key intermediate to substitute for deoxyribose, and controls the chlorination reaction conditions to obtain high purity alpha-substituted deoxyribose, the high purity alpha-substituted deoxyribose is conducive to coupling with silylation-protected 5-azacytidine to obtain high proportion of beta / alpha, and the dicitabine yield rate is increased.
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Paragraph 0037-0039; 0044-0046; 0051-0053
(2019/08/07)
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- Open-Close Strategy toward the Organocatalytic Generation of 2-Deoxyribosyl Oxocarbenium Ions: Pyrrolidine-Salt-Catalyzed Synthesis of 2-Deoxyribofuranosides
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The reaction of secondary amine salts with 2-deoxy-ribofuranoses under forcible conditions leads to the putative furanosyl oxocarbenium ion that is trapped with various alcohols to provide 2-deoxy-ribofuranosides. The observed anomeric selectivities range from an equimolar mixture to complete α-selectivity in the case of bulky sugar acceptors. Owing to the mechanism and temperature of the transformation, the generated oxocarbenium ion shows little or no facial preference towards the nucleophilic attack of non-carbohydrate acceptors and leads to a mixture of anomers in the case of benzyl and acetyl protected donors. However, the conformationally less flexible tetraisopropylsilyl protected donor reacted with both sugar and non-sugar acceptors in a stereoselective fashion. Besides, the glycosylation with 2-cyanoethanol gave the product with unexpected beta-selectivity presumably due to nitrile effect. The operationally simple organocatalytic protocol provides easy access to otherwise difficult 2-deoxy-ribofuranosides/disaccharides.
- Ghosh, Titli,Mukherji, Ananya,Kancharla, Pavan K.
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supporting information
p. 7488 - 7498
(2019/11/29)
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- SOLID STATE FORMS OF 5-CHLORO-6-[(2-IMINOPYRROLIDIN-1-YL)METHYL]PYRIMIDINE-2,4-(1H,3H)-DIONE HYDROCHLORIDE AND THEIR PROCESSES FOR THE PREPARATION THEREOF
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The present invention relates to solid state forms of 5-chloro-6-[(2-iminopyrrolidin-1-yl)methyl]pyrimidine-2,4-(1H,3H)-dione hydrochloride compound of formula-1a and their processes for the preparation thereof and an improved process for the preparation of 5-chloro-6-[(2-iminopyrrolidin-1-yl)methyl]pyrimidine-2,4-(1H,3H)-dione hydrochloride. The present inventors also provides an amorphous polymorph of the combination drug consisting of 2'-deoxy-5-(trifluoromethyl) uridine and 5-chloro-6-[(2-iminopyrrolidin-1-yl)methyl]pyrimidine-2,4-(1H,3H)-dione monohydrochloride and its process for the preparation.
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(2019/04/09)
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- Synthetic method of decitabine
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The present invention relates to a synthetic method of decitabine, and discloses a method for synthesizing a compound as shown in a formula I, The method comprises the steps of: reacting a compound IIwith a compound III by a following reaction in a solvent under the action of TMSOTf to obtain a compound I. The synthetic method of the invention has the advantages that the raw materials are easy toobtain, the operation is safe, the conditions are mild and easy to control, and a solid product obtained by an acylation protection is easy to be crystallized and purified, which is favorable for thenext reaction and improves the selectivity of a final beta-isomer product, no further conversion to hydroxymethyl is required, the reaction step is simplified, the reaction yield of each step is good, the atomic economy is high, and the method is suitable for a large number of industrial production and the like.
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Paragraph 0044-0045
(2019/08/01)
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- COMPOSITION COMPRISING PAEONIFLORIN OR ALBIFLORIN ANALOGUE, METHOD OF PREPARATION THEREOF
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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 20; 21
(2018/04/20)
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- Secondary amine salt catalyzed controlled activation of 2-deoxy sugar lactols towards alpha-selective dehydrative glycosylation
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A new organocatalytic glycosylation method exploiting the lactol functionality has been disclosed. The catalytic generation of glycosyl oxacarbenium ions from lactols under forcible conditions via weakly Br?nsted-acidic, readily available secondary amine salts affects the diastereoselective glycosylation of 2-deoxypyranoses and furanoses. This operationally simple iminium catalyzed activation of 2-deoxy hemi-acetals is a potential alternative to the existing cumbersome methods that need specialized handling. The mechanisms for this unique transformation and kinetic/thermodynamic effects have been discussed based on both experimental evidence and theoretical studies.
- Ghosh, Titli,Mukherji, Ananya,Srivastava, Hemant Kumar,Kancharla, Pavan K.
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supporting information
p. 2870 - 2875
(2018/05/03)
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- Zeolite-Based Organic Synthesis (ZeoBOS) of Acortatarin A: First Total Synthesis Based on Native and Metal-Doped Zeolite-Catalyzed Steps
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Similarly to polymer-supported assisted synthesis (PSAS), organic synthesis could be envisaged being performed by using zeolites, native or metal-doped, as heterogeneous catalysts. To illustrate this unprecedented Zeolite-Based Organic Synthesis (ZeoBOS),
- Wimmer, Eric,Borghèse, Sophie,Blanc, Aurélien,Bénéteau, Valérie,Pale, Patrick
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supporting information
p. 1484 - 1489
(2017/02/10)
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- Efficient preparation of 2-nitroimidazole nucleosides as precursors for hypoxia PET tracers
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Abstract: 2-Deoxy-D-ribose was converted to α/β-mixtures of methyl 3-O-acetyl- and methyl 3-O-benzoyl-2-deoxy-5-(p-toluenesulfonyl)-D-ribofuranosides. These were reacted with boron trichloride to generate ribofuranosyl chlorides, which afforded precursors for tracers to image tumor hypoxia on substitution with salts of 2-nitroimidazole. The anomeric ratio of the nucleosides was delicately influenced by the reaction conditions. Graphical abstract: [Figure not available: see fulltext.]
- Kri?ková, Petra,Wieczorek, Anna,Hammerschmidt, Friedrich
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- Stereocontrolled Synthesis of a Possible Stereoisomer of Laurenidificin and a Formal Total Synthesis of (+)-Aplysiallene Featuring a Stereospecific Ring Contraction
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We report a highly stereocontrolled total synthesis of one of the possible stereoisomers of laurenidificin. Highlights of the synthesis include the formation of the 2,6-dioxabicyclo[3.3.0]octane framework by a stereospecific bromolactonization-α-bromination-ring contraction sequence, followed by a stereoselective propargylation, an insertion of the Z-enyne side chain by a hydroindation/cross coupling reaction, and ethylation at C13 with an organocuprate reagent. While the synthetic compound was not identical to the natural product, the absolute stereochemistry of the natural product was proposed on the basis of NMR analyses. Moreover, a formal total synthesis of (+)-aplysiallene was achieved by extending the ring contraction strategy. (Chemical Equation Presented).
- Kobayashi, Shoji,Yokoi, Taiki,Inoue, Tomoharu,Hori, Yutaka,Saka, Tomoaki,Shimomura, Taiki,Masuyama, Araki
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p. 1484 - 1498
(2016/03/01)
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- A Fluorogenic Screening for Enantio- and Diastereoselectivity of 2-Deoxy- d -ribose-5-phosphate Aldolases
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A highly sensitive, fluorescence-based selectivity screening system for 2-deoxy-d-ribose-5-phosphate aldolases was realized by installing short, straightforward syntheses to fluorophore-coupled carbohydrates as d-ribose, l-ribose, and d-xylose. The substr
- Bisterfeld, Carolin,Küberl, Irene,Dick, Markus,Pietruszka, J?rg
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- A SITAR hamanaka process for the preparation of intermediates
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The invention discloses a preparation method of a decitabine intermediate compound 1-acetoxyl-2-deoxidized-3,5-bi-O-fluorene methyl cyslohexyl-D-ribofuranose. The structural formula of the compound is shown in img file='DDA0000455164900000011.TIF' wi='648' he='304'/, and the preparation method comprises the following steps: o-methylation of 2'-deoxidized-D-ribose 1-bit hydroxyl; b) protection of 3,5-bit hydroxyl; and c) acylation of 1-bit-O-methyl. The invention also discloses a method for preparing decitabine employing the intermediate as a raw material.
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Paragraph 0066-0068
(2016/10/08)
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- Decitabine a process for the preparation of
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The invention discloses a preparation method of decitabine. The preparation method comprises the steps: oxygen methylation of 1st-site hydroxyl of 2-deoxy-D-ribose; protection for hydroxyls on a 3rd site and a 5th site; acylation of 1st-site oxygen methyle; activation of 5-azacytosine; and coupled reaction of protected 2-deoxy-D-ribose and the activated 5-azacytosine, purification of a coupling product; deprotection; and obtaining of a target product. According to the preparation method, the purity of the decitabine is improved, the purification steps of a final product are simplified, and the product cost is lowered.
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Paragraph 0036; 0062-0063
(2018/07/10)
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- Efficient synthesis of fluorescent alkynyl C-nucleosides via Sonogashira coupling for the preparation of DNA-based polyfluorophores
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A facile and general procedure for the preparation of alkynyl C-nucleosides with varied fluorophores is presented. Sonogashira coupling was used as a key reaction to conjugate the dyes to an easily accessible ethynyl functionalized deoxyribose derivative.
- K?lmel, Dominik K.,Barandun, Luzi J.,Kool, Eric T.
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supporting information
p. 6407 - 6412
(2016/07/15)
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- A used with the industrial production method for the synthesis of
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The invention relates to a decitabine synthesis and industrial production method, which comprises the following steps of: using 2-Deoxy-D-ribose as a raw material, performing a reaction between the raw material and methanol to obtain glucoside, protecting 3,5-dihydroxy by the use of 9-fluorenylmethyloxycarbonyl, reacting with hydrogen chloride to obtain 1-chlorflurecol sugar, performing a reaction between 1-chlorflurecol sugar and silanized 5-azacytosine, carrying out deprotection, and refining to obtain decitabine. The invention is characterized in that stannic chloride is not required during the condensation reaction between 1-chlorflurecol sugar and silanized 5-azacytosine so as to avoid the problem of excessive contents of heavy metals in pharmaceutical materials; and simultaneously the amount of trimethylsilyl trifluoromethanesulfonate and reaction conditions are controlled so as to increase the body burden of beta in the product.
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Paragraph 0041; 0042; 0043
(2018/02/04)
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- 4'-SUBSTITUTED NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
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Provided is 4'-substituted nucleoside derivatives of Formula I and their use in the inhibition of HIV reverse transcriptase, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS and/or ARC.
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(2015/12/08)
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- Synthesis and DNA/RNA Binding Properties of Conformationally Constrained Pyrrolidinyl PNA with a Tetrahydrofuran Backbone Deriving from Deoxyribose
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Sugar-derived cyclic β-amino acids are important building blocks for designing of foldamers and other biomimetic structures. We report herein the first synthesis of a C-activated N-Fmoc-protected trans-(2S,3S)-3-aminotetrahydrofuran-2-carboxylic acid as a building block for Fmoc solid phase peptide synthesis. Starting from 2-deoxy-d-ribose, the product is obtained in a 6.7% overall yield following an 11-step reaction sequence. The tetrahydrofuran amino acid is used as a building block for a new peptide nucleic acid (PNA), which exhibits excellent DNA binding affinity with high specificity. It also shows preference for binding to DNA over RNA and specifically in the antiparallel orientation. In addition, the presence of the hydrophilic tetrahydrofuran ring in the PNA structure reduces nonspecific interactions and self-aggregation, which is a common problem in PNA due to its hydrophobic nature.
- Sriwarom, Pitchanun,Padungros, Panuwat,Vilaivan, Tirayut
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p. 7058 - 7065
(2015/07/28)
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- Triazolyl donor/acceptor chromophore decorated unnatural nucleosides and oligonucleotides with duplex stability comparable to that of a natural adenine/thymine pair
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We report the design and synthesis of triazolyl donor/acceptor unnatural nucleosides via click chemistry and studies on the duplex stabilization of DNA containing two such new nucleosides. The observed duplex stabilization among the self-pair/heteropair has been found to be comparable to that of a natural A/T pair. Our observations on the comparable duplex stabilization has been explained on the basis of possible π-π stacking and/or charge transfer interactions between the pairing partners. The evidence of ground-state charge transfer complexation came from the UV-vis spectra and the static quenching of fluorescence in a heteropair. We have also exploited one of our unnatural DNAs in stabilizing abasic DNA.
- Bag, Subhendu Sekhar,Talukdar, Sangita,Matsumoto, Katsuhiko,Kundu, Rajen
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p. 278 - 291
(2013/02/25)
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- Cyclometalated iridium(III) complexes with deoxyribose substituents
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Fundamental study of enzymatic nucleoside transport suffers for lack of optical probes that can be tracked noninvasively. Nucleoside transporters are integral membrane glycoproteins that mediate the salvage of nucleosides and their passage across cell mem
- Maity, Ayan,Choi, Jung-Suk,Teets, Thomas S.,Deligonul, Nihal,Berdis, Anthony J.,Gray, Thomas G.
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p. 15924 - 15932
(2014/04/03)
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- Design, synthesis, and biological evaluation of C1-phosphonamidate analogues of 2-deoxy-d-ribose-1-phosphate
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A novel series of phenoxy C1-phosphonamidate derivatives of 2-deoxy-d-ribose have been synthesised as stable analogues of 2-deoxy-α-d-ribose-1-phosphate. A number of synthetic routes were explored for the preparation of these targets. The successful approach involved the synthesis of a protected C1-phosphonate ester 17 via Michaelis-Arbuzov reaction, which was then hydrolysed and coupled with different amino acid esters using aldrithiol. Subsequent hydrogenolysis afforded the targets 2a-g, which were isolated as a mixture of diastereoisomers. The compounds were assayed for inhibition of thymidine phosphorylase (TP) and uridine phosphorylase (UP) and for antiviral and cytostatic activity.
- Quintiliani, Maurizio,Balzarini, Jan,McGuigan, Christopher
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p. 9111 - 9119
(2013/09/24)
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- Synthetic approaches to a chiral 4-amino-3-hydroxy piperidine with pharmaceutical relevance
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Four synthetic strategies were evaluated towards the preparation of (-)-(3R,4R)-1-benzyl-4-(benzylamino)piperidin-3-ol (1), which was constructed with control over the relative and absolute stereochemistry of the 4,3-amino alcohol moiety. The first strategy employed a novel RhI catalyzed asymmetric hydrogenation, while two other strategies exploited the existing stereochemistry in 2-deoxy-d-ribose, and the fourth explored both biocatalytic and classical resolution techniques as a means to impart enantioenrichment to racemic intermediates en route to targeted structure (-)-1. The Royal Society of Chemistry 2012.
- Ortiz, Adrian,Young, Ian S.,Sawyer, James R.,Hsiao, Yi,Singh, Amarjit,Sugiyama, Masano,Corbett, R. Michael,Chau, Melissa,Shi, Zhongping,Conlon, David A.
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supporting information; experimental part
p. 5253 - 5257
(2012/08/08)
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- Influence of the nucleobase and anchimeric assistance of the carboxyl acid groups in the hydrolysis of amino acid nucleoside phosphoramidates
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Nucleoside phosphoramidates (NPs) are a class of nucleotide analogues that has been developed as potential antiviral/antitumor prodrugs. Recently, we have shown that some amino acid nucleoside phosphoramidates (aaNPs) can act as substrates for viral polymerases like HIV-1 RT. Herein, we report the synthesis and hydrolysis of a series of new aaNPs, containing either natural or modified nucleobases to define the basis for their differential reactivity. Aqueous stability, kinetics, and hydrolysis pathways were studied by NMR spectroscopy at different solution pD values (5-7) and temperatures. It was observed that the kinetics and mechanism (P-N and/or P-O bond cleavage) of the hydrolysis reaction largely depend on the nature of the nucleobase and amino acid moieties. Aspartyl NPs were found to be more reactive than Gly or β-Ala NPs. For aspartyl NPs, the order of reactivity of the nucleobase was 1-deazaadenine>7- deazaadenine>adenine>thymine≥3-deazaadenine. Notably, neutral aqueous solutions of Asp-1-deaza-dAMP degraded spontaneously even at 4°C through exclusive P-O bond hydrolysis (a 50-fold reactivity difference for Asp-1-deaza-dAMP vs. Asp-3-deaza-dAMP at pD 5 and 70°C). Conformational studies by NMR spectroscopy and molecular modeling suggest the involvement of the protonated N3 atom in adenine and 1- and 7-deazaadenine in the intramolecular catalysis of the hydrolysis reaction through the rare syn conformation. Touching (nucleo)base: A dual intramolecular catalytic influence is demonstrated by the nucleobase and carboxyl groups in the chemical hydrolysis of amino acid nucleoside phosphoramidate prodrugs (see scheme). The replacement of the adenine N1 or N7 atoms instead of the N3 atom is shown to have a conformational role in which the protonated N3 is crucial in regulating the kinetics and mechanism of nucleotide (P-N pathway) versus nucleoside (P-O pathway) formation. Copyright
- Maiti, Munmun,Michielssens, Servaas,Dyubankova, Natalia,Maiti, Mohitosh,Lescrinier, Eveline,Ceulemans, Arnout,Herdewijn, Piet
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supporting information; experimental part
p. 857 - 868
(2012/03/26)
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- Synthesis and evaluation of 6-Aza-2′-deoxyuridine monophosphate analogs as inhibitors of thymidylate synthases, and as substrates or inhibitors of thymidine monophosphate kinase in mycobacterium tuberculosis
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A series of 5-substituted analogs of 6-aza-2′-deoxyuridine 5′-monophosphate, 6-aza-dUMP, has been synthesized and evaluated as potential inhibitors of the two mycobacterial thymidylate synthases (i.e., a flavin-dependent thymidylate synthase, ThyX, and a classical thymidylate synthase, ThyA). Replacement of C(6) of the natural substrate dUMP by a N-atom in 6-aza-dUMP 1a led to a derivative with weak ThyX inhibitory activity (33% inhibition at 50 μM). Introduction of alkyl and aryl groups at C(5) of 1a resulted in complete loss of inhibitory activity, whereas the attachment of a 3-(octanamido)prop-1-ynyl side chain in derivative 3 retained the weak level of mycobacterial ThyX inhibition (40% inhibition at 50 μM). None of the synthesized derivatives displayed any significant inhibitory activity against mycobacterial ThyA. The compounds have also been evaluated as potential inhibitors of mycobacterial thymidine monophosphate kinase (TMPKmt). None of the derivatives showed any significant TMPKmt inhibition. However, replacement of C(6) of the natural substrate (dTMP) by a N-atom furnished 6-aza-dTMP (1b), which still was recognized as a substrate by TMPKmt. Copyright
- Koegler, Martin,Busson, Roger,De Jonghe, Steven,Rozenski, Jef,Van Belle, Kristien,Louat, Thierry,Munier-Lehmann, Helne,Herdewijn, Piet
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experimental part
p. 536 - 556
(2012/05/20)
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- A dramatic concentration effect on the stereoselectivity of N-glycosylation for the synthesis of 2′-deoxy-β-ribonucleosides
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A dramatic concentration effect on the stereoselectivity of N-glycosylation, which is attributable to a low-concentration-facilitated remote-participation, has been disclosed, leading to convenient synthesis of the 2′-deoxy-β-ribonucleosides of biological significance. The Royal Society of Chemistry 2012.
- Yang, Fei,Zhu, Yugen,Yu, Biao
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supporting information; scheme or table
p. 7097 - 7099
(2012/08/07)
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- A highly fluorescent DNA toolkit: Synthesis and properties of oligonucleotides containing new Cy3, Cy5 and Cy3B monomers
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Cy3B is an extremely bright and stable fluorescent dye, which is only available for coupling to nucleic acids post-synthetically. This severely limits its use in the fields of genomics, biology and nanotechnology. We have optimized the synthesis of Cy3B, and for the first time produced a diverse range of Cy3B monomers for use in solid-phase oligonucleotide synthesis. This molecular toolkit includes phosphoramidite monomers with Cy3B linked to deoxyribose, to the 5-position of thymine, and to a hexynyl linker, in addition to an oligonucleotide synthesis resin in which Cy3B is linked to deoxyribose. These monomers have been used to incorporate single and multiple Cy3B units into oligonucleotides internally and at both termini. Cy3B Taqman probes, Scorpions and HyBeacons have been synthesized and used successfully in mutation detection, and a dual Cy3B Molecular Beacon was synthesized and found to be superior to the corresponding Cy3B/DABCYL Beacon. Attachment of Cy3, Cy3B and Cy5 to the 5-position of thymidine by an ethynyl linker enabled the synthesis of an oligonucleotide FRET system. The rigid linker between the dye and nucleobase minimizes dye-dye and dye-DNA interactions and reduces fluorescence quenching. These reagents open up new future applications of Cy3B, including more sensitive single-molecule and cell-imaging studies. The Author(s) 2012.
- Hall, Lucy M.,Gerowska, Marta,Brown, Tom
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- PROCESS FOR THE PREPARATION OF (2R.3S)-2-(HYDROXYMETHYL) -5-METHOXYTETRAHYDROFURAN-3-OL AND ACETYLATED DERIVATIVES THEREOF, FREE OF PYRANOSE COMPOUNDS
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A method of preparing a ribofuranose derivative essentially free of pyranose compounds includes a step of contacting a solution of MDR containing MDRP as an impurity in a solvent including methanol and/or tetrahydrofuran with at least one alkali metal periodate under conditions sufficient to oxidize at least a portion of the MDRP. MDR containing at most 5 wt% of MDRP based on the total weight of MDR and MDRP may be produced.
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Page/Page column 5-6; 8
(2012/06/15)
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- A new DNA building block, 4′-selenothymidine: Synthesis and modification to 4′-seleno-AZT as a potential anti-HIV agent
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The first synthesis of 4′-selenothymidine (1), a novel DNA building block, and 4′-seleno-AZT (2) was accomplished from 2-deoxy-d-ribose via stereoselective formation of 2-deoxy-4-seleno-d-furanose 17 and a Pummerer-type base condensation as key steps. 4′-
- Alexander, Varughese,Choi, Won Jun,Chun, Jeongha,Kim, Hea Ok,Jeon, Ji Hye,Tosh, Dilip K.,Lee, Hyuk Woo,Chandra, Girish,Choi, Jungwon,Jeong, Lak Shin
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supporting information; experimental part
p. 2242 - 2245
(2010/08/05)
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- Novel exocyclic nucleoside related to clitocine: A convergent synthesis of 3-azido-2,3-dideoxy clitocine
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The synthesis of a new clitocine derivative was achieved through a convergent strategy. A protected 4,6-diamino-5-nitropyrimidine was condensed with p-chlorobenzoyl (PCB)-protected methyl 3'-azido-2',3'- dideoxyribofuranoside, followed by subsequently deprotection to give the desired product. Georg Thieme Verlag Stuttgart.
- Guo, Xianghai,Liu, Can,Zheng, Lanxi,Jiang, Shende,Shen, Jiaxiang
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experimental part
p. 1959 - 1962
(2010/10/02)
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- PREPARATION OF DECITABINE
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The present application relates to processes for the preparation and purification of decitabine, and to processes for the preparation of a crystalline form of decitabine.
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Page/Page column 24-25
(2010/11/18)
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- Design of novel RNA ligands that bind stem-bulge HIV-1 TAR RNA
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We report here the rational design and the synthesis of a new series of RNA ligands. These molecules are constituted of various binding motifs that interact cooperatively with HIV-1 TAR RNA, used as a model.
- Duca, Maria,Malnuit, Vincent,Barbault, Florent,Benhida, Rachid
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supporting information; scheme or table
p. 6162 - 6164
(2010/11/04)
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- PROCESSES FOR PRODUCING DECITABINE
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New processes for producing decitabine are provided.
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Page/Page column 4
(2010/10/19)
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- A greener enantioselective synthesis of the antiviral agent North-methanocarbathymidine (N-MCT) from 2-deoxy-d-ribose
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An enantioselective synthesis of suitably protected (1R,2S,4S,5S)-4-amino-1-(hydroxymethyl)bicyclo[3.1.0]hexan-2-ol, a key starting material for the synthesis of conformationally locked carbocyclic nucleosides, including the antiviral active North-methano
- Ludek, Olaf R.,Marquez, Victor E.
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experimental part
p. 8461 - 8467
(2009/12/28)
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- Synthesis of (+)-obtusenyne
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An enantioselective synthesis of the halogenated medium-ring ether natural product (+)-obtusenyne is reported which uses the ring expansion of a seven-membered ketene acetal by means of a Claisen rearrangement to construct the core nine-membered oxygen he
- Mak, S.Y. Frankie,Curtis, Neil R.,Payne, Andrew N.,Congreve, Miles S.,Wildsmith, Andrew J.,Francis, Craig L.,Davies, John E.,Pascu, Sofia I.,Burton, Jonathan W.,Holmes, Andrew B.
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supporting information; experimental part
p. 2867 - 2885
(2009/06/17)
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- Total synthesis of haterumalides NA and NC via a chromium-mediated macrocyclization
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The syntheses of haterumalides NA and NC were accomplished via the macrocyclization of a chlorovinylidene chromium carbenoid onto a pendant aldehyde to generate the C8-C9 bond with the desired stereoisomer as the major product. Utilizing the latter chemistry enables access to both C9 hydroxylated (haterumalides NC and ND) and C9 deoxygenated forms (haterumalides NA, NB, and NE; via deoxygenation of the C9-hydroxyl). Copyright
- Schomaker, Jennifer M.,Borhan, Babak
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scheme or table
p. 12228 - 12229
(2009/02/05)
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- Synthesis of different 3,5-diazidofuranoses: A new and general synthesis pathway
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Diamino- and diazidofuranoses represent useful precursors, for example, for the synthesis of substituted nucleosides and metal complexes, respectively. Known procedures for their synthesis lack the availability of cheap starting materials, adequate yields, and the access to all possible diastereomeres. Therefore, 3,5-diazido-3,5-dideoxy- and -2,3,5-trideoxyfuranoses both with ribo- and xylo-configuration were prepared using different approaches.
- Koth, Daniel,Fiedler, Andrea,Scholz, Sandy,Gottschaldt, Michael
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p. 267 - 278
(2008/02/12)
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- Studies on the generation of unnatural C-nucleosides with 1-alkynyl-2-deoxy-D-riboses
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(Chemical Equation Presented) 1-Alkynyl-2-deoxy-D-riboses 7 and 8 were independently synthesized and subsequently used to generate several novel C-nucleosides.
- Adamo, Mauro F. A.,Pergoli, Roberto
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p. 4443 - 4446
(2008/03/12)
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- Enantiospecific synthesis of the heparanase inhibitor (+)-trachyspic acid and stereoisomers from a common precursor
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The total synthesis of natural (+)-trachyspic acid and its enantiomer is described starting from a common 2-deoxy-d-ribose derivative. The synthesis of the corresponding C3 epimers from the same starting material is also described. Each stereoisomer was a
- Zammit, Steven C.,Ferro, Vito,Hammond, Edward,Rizzacasa, Mark A.
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p. 2826 - 2834
(2008/03/14)
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- Prodan-containing nucleotide and use thereof
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A compound represented by formula (1): wherein R1 is a substituent represented by formula (2): wherein R2 is ═O or —NH2, with the proviso that when R2 is ═O, H is attached to the 1-position N of the pyrimidine ring, and the bond between the 1-position N and the 6-position C is a single bond; or a substituent represented by formula (3): wherein R3 is —OH, ═O, or —NH2, with the proviso that when R3 is —OH or —NH2, R4 is H; when R3 is ═O, R4 is —NH2; and when R3 is ═O, H is attached to the 1-position N of the purine ring, and the bond between the 1-position N and the 6-position C is a single bond.
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Page/Page column 17-18; sheet 1
(2008/06/13)
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- Differential solvation and tautomer stability of a model base pair within the minor and major grooves of DNA
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2-(2′-Hydroxyphenyl)benzoxazole (HBO) may be used as a model base pair to study solvation, duplex environment, and tautomerization within the major and minor groves of DNA duplexes. In its ground state, HBO possesses an enol moiety which may be oriented s
- Dupradeau, Francois-Yves,Case, David A.,Yu, Chengzhi,Jimenez, Ralph,Romesberg, Floyd E.
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p. 15612 - 15617
(2007/10/03)
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- Introduction of peptide functions into DNA by nucleic acid peptides, NAPs
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Nucleic acid peptides (NAPs) with a mimetic amino acid side residue at the base position of the nucleotide via an amide bond were synthesized from 3-deoxy-6-O-(4,4′-dimethoxytrityl)allonic acid methyl ester as the common precursor. Furthermore, an NAP with an octapeptide at the C1′ position was synthesized. The peptide-linked NAP exhibits both functions of the oligopeptide part and of the oligonucleotide part. Copyright
- Kawakami, Junji,Wang, Zhong-Ming,Fujiki, Hiroyoshi,Izumi, Satoshi,Sugimoto, Naoki
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p. 1554 - 1555
(2007/10/03)
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- A parallel synthesis approach towards a family of C-nucleosides
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A synthetic route was devised for a sugar based α-chloroketone, which was subsequently used to generate a family of C-nucleosides via parallel synthetic methodology.
- Adamo, Mauro F.A.,Adlington, Robert M.,Baldwin, Jack E.,Day, Anna L.
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p. 841 - 849
(2007/10/03)
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- Convenient synthesis of 2′-deoxy-2-fluoroadenosine from 2-fluoroadenine
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A convenient synthesis of 2′-deoxy-2-fluoroadenosine from commercially available 2-fluoroadenine is described. The coupling reaction of silylated 2-fluoroadenine with phenyl 3,5-bis[O-(t-butyldimethylsilyl)]-2-deoxy-1-thio- D-erythro-pentofuranoside gave
- Ye, Song,Rezende, Martha M.,Deng, Wei-Ping,Kirk, Kenneth L.
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p. 1899 - 1905
(2007/10/03)
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- Synthesis and Characterization of Oligonucleotides Containing the C4′-Oxidized Abasic Site Produced by Bleomycin and Other DNA Damaging Agents
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Selective introduction of damage: The C4′-position of DNA serves as the site of attack for a number of DNA damaging agents, including bleomycin. The C4′-abasic site is a major product found in damaged DNA following abstraction of the hydrogen atom from th
- Kim, Jaeseung,Gil, Jun Mo,Greenberg, Marc M.
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p. 5882 - 5885
(2007/10/03)
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- A Convenient Synthesis of Protoanemonin
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A new convenient synthesis of protoanemonin (1) starting from 2-deoxy-D-ribose (3) is described. A key step in the sequence is the successive β- and δ-eliminations of 3,5-di-O-p-toluoyl-2-deoxy-D-ribono-1,4-lactone (6).
- Crey, Caroline,Dumy, Pascal,Lhomme, Jean,Kotera, Mitsuharu
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p. 3727 - 3732
(2007/10/03)
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