147058-39-7Relevant academic research and scientific papers
Stereoselective syntheses of β-L-FD4C and β-L-FddC
Chen, Shu-Hui,Li, Xiuyan,Li, Jun,Niu, Chuansheng,Carmichael, Ellen,Doyle, Terrence W.
, p. 3449 - 3452 (2007/10/03)
Stereocontrolled syntheses of two potent antiviral agents, β-L-FD4C and β-L-FddC, were accomplished both in 10-step sequences, with an overall yield of 27% and 25%, respectively. It is worthwhile to mention that the introduction of a phenylseleno moiety to the C-2α position of the lactone 4 can now be performed in a stereocontrolled fashion, providing the key intermediate 5α in 75% yield.
Synthesis of Several Pyrimidine L-Nucleoside Analogues as Potential Antiviral Agents
Lin, Tai-Shun,Luo, Mei-Zhen,Liu, Mao-Chin
, p. 1055 - 1068 (2007/10/02)
β-L-5-Iodo-2'-deoxyuridine (β-L-IUdR, 7) and 1-uracil (β-L-BV-ara-U, 10) have been synthesized via a multi-step synthesis from L-arabinose. 2',3'-Dideoxy-β-L-5-azacytidine (18), 2',3'-dideoxy-β-L-2-thiocytidine (20) and their respective α-anomers, compounds 19 and 21, also were synthesized by direct coupling of 1-O-acetyl-5-O-(tert-butyldimethylsilyl)-2,3-dideoxy-L-ribofuranose (13) with the corresponding silylated bases, in the presence of EtAlCl2 in CH2Cl2, followed by separation of the α- and β-isomers and deblocking of the 5'-protecting groups.In addition, 2',3'-dideoxy-β-L-5-fluorocytidine (34), a potent anti-HIV and anti-HBV agent, was synthesized by an alternative methodology from 2',3'-dideoxy-β-L-5-fluorouridine (31) via a 4-triazolylpyrimidinone intermediate.These L-nucleoside analogues were tested in vitro against HIV, HBV, HSV-1, and HSV-2.Among these compounds, 2',3'-dideoxy-β-L-5-azacytidine (18) was found to show significant activity against HBV in vitro at approximately the same level as 2',3'-dideoxy-β-D-cytidine (ddC), which is a known potent anti-HBV agent.
Anti-HIV and Anti-HBV Activities of L-2',3'-dideoxynucleoside Analogues: ddC, 5FddC, 5-Aza ddC and ddG
Mansour, Tarek S.,Tse, Allan,Charron, Marie,Hooker, Elizabeth U.,Ashman, Clare,et al.
, p. 417 - 425 (2007/10/03)
The antiviral activities of the L-enantiomers of the title nucleoside analogues were determined in vitro. β-L-ddC and β-L-5FddC showed significant activity against the replication of HIV-1 and HBV, whereas β-L-5-aza ddC and β-L-ddG were devoid of such activities.
2'- and/or 3'-deoxy-β-L-pentofuranosyl nucleoside derivatives: Stereospecific synthesis and antiviral activities
Gosselin,Mathe,Bergogne,Aubertin,Kirn,Sommadossi -,Schinazi,Imbach
, p. 611 - 617 (2007/10/02)
Several L-enantiomers of nucleoside analogues were stereospecifically synthesized by a multi-step reaction from L-xylose and their antiviral properties were examined in vitro. Two of them, namely β-L-2',3,'- dideoxycytidine (β-L-ddC) and its 5-fluoro derivative (β-L-FddC) were found to have potent anti-human immunodeficiency virus (HIV) and significant antihepatitis B virus (HBV) activities in cell cultures.
Diastereocontrol in Glycosylation Reactions: Synthesis of β-D and β-L Dideocytidine Analogues
Tse, Allan,Mansour, Tarek S.
, p. 7807 - 7810 (2007/10/02)
Expeditious and diastereoselective total syntheses of the antiviral agents, β-L-ddC, β-L-5FddC and β-D-5FddC have been achieved in four steps from commercially available R-(-)-5-oxo-2-tetrahydrofurancarboxylic and its 2S isomer respectively.
Synthesis and biological evaluation of 2',3'-dideoxy-L-pyrimidine nucleosides as potential antiviral agents against human immunodeficiency virus (HIV) and hepatitis B virus (HBV)
Lin,Luo,Liu,Pai,Dutschman,Cheng
, p. 798 - 803 (2007/10/02)
Various 2',3'-dideoxy-L-cytidine, 2',3'-dideoxy-L-uridine, and 3'-deoxy- L-thymidine analogues have been synthesized and evaluated in vitro as potential anti-HIV and anti-HBV agents. Coupling of 1-O-acetyl-5-O-(tert- butyldimethylsilyl)-2,3-dideoxy-L-ribofuranose (1) with silylated derivatives of 5-fluorocytosine, cytosine, 5-fluorouracil, uracil, and thymine in the presence of ethylaluminum dichloride gave the corresponding nucleosides 2, 3, 4, 5, 10, 11, 12, 16, 17, and 18 as a mixture of α- and β-anomers, which were then deblocked to yield the corresponding 2',3'-dideoxy-L-5- fluorocytidine derivatives, 6 and 7, 2',3'-dideoxy-L-cytidine derivatives, 8 and 9, 2',3'-dideoxy-β-L-fluorouridine (13), 2',3'-dideoxy-β-L-uridine (14), and 3'-deoxy-L-thymidine derivatives, 15 and 19. Among these 2',3'- dideoxy-L-nucleoside analogues, 2',3'-dideoxy-β-L-5-fluorocytidine (6, β- L-FddC) was found to be the most active against HIV-1, which is approximately 3 and 4 times more active against HIV-1 in vitro than 2',3'-dideoxy-β-D- cytidine (ddC) and 2',3'-dideoxy-β-D-5-fluorocytidine (β-D-FddC) with ED50 values of 0.5, 1.5, and 2 μM, respectively. The dose-limiting toxicity of ddC is severe neuropathy which may be caused by the inhibition of the synthesis of mitochondrial DNA. ddC has an IC50 value of 0.022 μM against host mitochondrial DNA synthesis. Conversely, the IC50 values for β-L-FddC and β-L-ddC are >100 μM; therefore, neuropathy may not present itself to be a problem with β-L-FddC and β-L-ddC as chemotherapeutic agents. In addition, β-L-FddC and 2',3'-dideoxy-β-L-cytidine (8,β-L-ddC) demonstrated equally potent activity against HBV in vitro by having the same ED50 value of 0.01 μM. Both β-L-FddC and β-L-ddC, which have an 'unnatural' L-configuration in the sugar moiety, are ~1000 and 280 times more potent, respectively, against HBV than the D-configuration β-D-FddC and ddC which have an ED50 values of 10 and 2.8 μM. In view of the potent antiviral activity of β-L-FddC against both HIV-1 and HBV and potent antiviral activity of β-L-ddC against HBV in vitro, their low cytotoxicity, and especially the negligible inhibitory effect on host mitochondrial DNA synthesis, β-L-FddC and β-L-ddC merit further development as potential anti-HIV and anti-HBV agents.
Synthesis and biological evaluation of pyrimidine and purine α-L-2',3'- dideoxy nucleosides
Van Draanen,Koszalka
, p. 1679 - 1693 (2007/10/02)
A series of α-L-2',3'-dideoxy nucleosides was prepared as potential antiviral agents. The pyrimidine nucleosides were prepared by standard Vorbruggen coupling reactions. The purine analogues were prepared by enzymatic transfer of the dideoxy sugar from a pyrimidine to a purine base. These compounds were inactive against HIV-1, HBV, HSV-1 and -2, VZV, and HCMV.
