- 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; 0040-0041; 0044; 0047-0048; 0051; 0054-0055
(2019/08/07)
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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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Page/Page column 39-40
(2019/04/09)
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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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supporting information
p. 2044 - 2050
(2016/04/05)
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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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Page/Page column 29; 30
(2015/12/08)
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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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- 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 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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- 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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- 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 18; sheet 1
(2008/06/13)
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- Efficient Preparation of 2-Deoxy-3,5-di-O-p-toluoyl-α-D- ribofuranosyl Chloride
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An efficient method for the synthesis of 1-O-methyl-3,5-di-O-p-toluoyl-2- deoxy-α/β-D-ribose is described. Upon treatment with HCl, 2-deoxy-3,5-di-O-p-toluoyl-α-D-ribofuranosyl chloride, previously unstable, was produced as a white solid, stable in air indefinitely.
- Dhimitruka, Ilirian,SantaLucia Jr., John
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p. 335 - 337
(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 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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- 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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p. 4571 - 4574
(2007/10/03)
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- Convenient preparation of 2-deoxy-3,5-di-O-p-toluoyl-α-D-erythro-pentofuranosyl chloride
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By using acetyl chloride as HCl generator, the procedure for the Hoffer preparation of the α-chloro sugar 4a was significantly improved. The α-configuration of the chloro atom was confirmed by using NOE measurement. Sequential transformation of 4a to the β-anomer and to the furfuryl derivative 6 was studied.
- Rolland, Valerie,Kotera, Mitsuharu,Lhomme, Jean
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p. 3505 - 3511
(2007/10/03)
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- Hydantoin Analogues of Thymidine
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Hydantoin nucleosides were synthesized from a protected methyl 2-deoxy-D-ribofuranoside in a Friedel-Crafts catalyzed silyl-Hilbert-Johnson reaction as modified by Vorbrueggen.Atypical byproducts are accounted for by assuming the initial step being a ring opening of the sugar to give an acyclic glycos-1-yl cation.
- El-Barbary, Ahmed A.,Khodair, Ahmed I.,Pedersen, Erik B.
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p. 5994 - 5999
(2007/10/02)
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