92562-88-4Relevant academic research and scientific papers
Synthesis study of 3′-α-fluoro-2′,3′- dideoxyguanosine
Torii, Takayoshi,Onishi, Tomoyuki,Tanji, Shigehisa,Izawa, Kunisuke
, p. 1051 - 1054 (2005)
A synthetic method was established for 3′-α-fluoro-2′, 3′-dideoxyguanosine 1 from guanosine 2 in 27% overall yield and 6 steps. A byproduct 6a of fluorination was identified by NMR studies, its presence strongly supporting our supposition that the fluorination itself proceeded via a bromonium cation. Copyright Taylor & Francis, Inc.
SYNTHESIS OF FLG
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Page/Page column 11, (2012/09/11)
The present invention concerns the synthesis of substantially anomerically pure 2,3-dideoxy-3- fluoro-5-0-(4-phenylbenzoyl)-a-D-erythropentofuranosyl chloride from an α/β-mixture of the corresponding methyl glycoside. The method of the invention provides the pure a-chloride without the need of anomeric separation. The α-chloride thus achieved is suitable for use as glycosyl donor in the preparation of 2',3'-dideoxy-3'-fluoro nucleosides. In particular, the preparation of 2',3'-dideoxy-3 '-fluoroguanosine, FLG, using an α/β-mixture of the methyl glycoside without the need of anomeric separation is disclosed.
Synthesis of the hepatitis B nucleoside analogue lagociclovir valactate
Brodszki, Martin,Baeckstroem, Birthe,Malmgren, Hakan,Wennerberg, Johan,Larsson, Torbjoern,Pelcman, Mikael,Waehling, Horst,Wallberg, Hans,Horvath, Karol
experimental part, p. 1027 - 1032 (2012/01/04)
2′,3′-Dideoxy-3′-fluoro-5-O-[(S)-(+)-2-(l-valyloxy) -propionyl guanosine (lagociclovir valactate) is a prodrug of 3′-fluoro-2′,3′-dideoxyguanosine with high oral bioavailability in humans and potent activity against hepatitis B virus (HBV). A five-step synthesis of lagocyclovir valactate starting from 2-amino-6-chloropurine is described. The synthesis was performed at kilogram scale, and the target nucleoside prodrug was isolated as the hemisulphate salt with an overall yield of 23%. The major challenges were N-glycosylation of a 2-deoxyfluorosugar, which required separation of α- and β-anomers, and deprotection of the penultimate intermediate by hydrogenation.
Production method of fluorinated purine nucleoside derivative, intermediate therefor and production method thereof
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Page/Page column 18, (2008/06/13)
Purine nucleosides which are fluorinated at the 3′-position (preferably the α-position), may be economically and efficiently produced by fluorinating a novel purine nucleoside derivative (1) in which the hydroxyl group at the 5′-position is protected to obtain a novel purine nucleoside derivative (2) in a high yield. The derivative (2) is subjected to desulfurization, deprotection of R1 and, as necessary protection, deprotection, or modification of nucleic acid base moiety, to obtain the desired purine nucleoside (3). wherein each symbol is as defined in the specification.
Production method of fluorinated purine nucleoside derivative, intermediate therefor and production method thereof
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Page/Page column 30, (2008/06/13)
Purine nucleosides which are fluorinated at the 3'-position (preferably the α-position), may be economically and efficiently produced by fluorinating a novel purine nucleoside derivative (1) in which the hydroxyl group at the 5'-position is protected to obtain a novel purine nucleoside derivative (2) in a high yield. The derivative (2) is subjected to desulfurization, deprotection of R1 and, as necessary protection, deprotection, or modification of nucleic acid base moiety, to obtain the desired purine nucleoside (3). wherein each symbol is as defined in the specification.
A concise synthesis of 3′-α-fluoro-2′,3′-dideoxyguanosine (FddG) via 3′-α-selective fluorination of 8,2′-thioanhydronucleoside
Torii, Takayoshi,Onishi, Tomoyuki,Izawa, Kunisuke,Maruyama, Tokumi
, p. 6139 - 6141 (2007/10/03)
The antiviral nucleoside 3′-α-fluoro-2′,3′-dideoxyguanosine (FddG) was synthesized via 3′-α-selective fluorination of 8,2′-thioanhydronucleoside as the key step. Desulfurization of 3′-α-fluoro-3′-deoxy-8,2′-thioanhydronucleoside could be achieved by the treatment with Raney Ni in toluene. This method provides a concise route to 3′-α-fluoro-2′,3′-dideoxynucleosides that avoids the use of explosive and expensive SF4-related fluorinating reagents.
Synthesis of 6-arylthio analogs of 2′,3′-dideoxy-3′- fluoroguanosine and their effect against hepatitis B virus replication
Torii, Takayoshi,Onishi, Tomoyuki,Izawa, Kunisuke,Maruyama, Tokumi,Demizu, Yosuke,Neyts, Johan,De Clercq, Erik
, p. 655 - 665 (2008/02/08)
A key compound, 2-amino-6-chloro-9-(2,3-dideoxy-3-fluoro-β-D- erythro-pentofuranosyl)purine, was prepared from 2-amino-6-chloropurine riboside in 5 steps, then subjected to the nucleophilic displacement with benzenethiols to afford 6-arylthio congeners. These compounds showed a similar anti-HBV effect to that of 2′,3′-dideoxy-3′-fluoroguanosine. Copyright Taylor & Francis Group, LLC.
Chemo-enzymatic synthesis of 2′,3′-dideoxy-3′-fluoro-β-D-guanosine via 2,3-dideoxy-3-fluoro-α-D-ribose 1-phosphate
Komatsu, Hironori,Araki, Tadashi
, p. 2899 - 2901 (2007/10/03)
2,3-Dideoxy-3-fluoro-α-D-ribose 1-phosphate 2 was stereoselectively synthesized and converted to 2′,3′-dideoxy-3-fluoro-β-D-guanosine 1 by enzymatic reaction using purine nucleoside phosphorylase. This chemo-enzymatic strategy was first applied to the synthesis of 1.
Method of treating viral infections in humans and compositions therefor
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, (2008/06/13)
A method of treating viral diseases in a human subject is disclosed. The method involves applying effective amounts of the compound: STR1 wherein X is an azido group, a methoxy radical or a fluorine atom and B is thymine, uracil, guanine, cytosine, purine or hypoxanthine if X is methoxy or fluorine, and B is guanine, purine or hypoxanthine if X is azido or a pharmaceutically acceptable salt thereof. Also disclosed are compositions and compounds useful in the method.
Synthesis and anti-HIV activity of different sugar-modified pyrimidine and purine nucleosides
Herdewijn,Balzarini,Baba,Pauwels,Van Aerschot,Janssen,De Clerq
, p. 2040 - 2048 (2007/10/02)
A series of base-modified pyrimidine 3'-azido-2',3'-dideoxynucleosides and 3'-substituted purine and pyrimidine 2',3'-dideoxynucleosides have been synthesized and evaluated for their inhibitory activity against human immunodeficiency virus (HIV) replication in MT-4 cells. The following pyrimidine derivatives emerged as the most potent and/or selective inhibitors of HIV-induced cytopathogenicity (in order of decreasing selectivity: 3'-azido-3'-deoxythymidine (AZT), 3'-azido-2',3'-dideoxyuridine (AzddUrd), 3'-azido-2',3'-dideoxy-5-methylcytidine (AzddMeCyd), 3'-fluoro-ddUrd (FddUrd), 3'-fluoro-ddThd (FddThd), the N4-hydroxylated derivative of AzddMeCyd and the N4-methylated derivative of AzddMeCyd. Among the purine 2',3'-dideoxynucleosides, 3'-azido-2',3'-dideoxyguanosine (AzddGuo), 3'-fluoro-ddGuo (FddGuo), and 3'-fluoro-2,6-diaminopurine 2',3'-dideoxynucleoside (FddDAPR) were the most selective inhibitors of HIV replication.
