Synthesis and properties of (alpha-P-borano)-nucleoside 5'-triphosphate analogues as potential antiviral agents.
The alpha-P-borano modification, where one of the alpha-phosphate oxygens is replaced by borane, of chain terminating nucleoside triphosphates are currently being tested in cell culture and are showing promise as effective viral polymerase inhibitors. The goal of this project is to combine the alpha-P-borano and Nanogel drug delivery technology to increase the antiviral potency of chain terminating sugar and base modified purine nucleosides versus the Hepatitis C Viral RNA dependent RNA polymerase (HCV RdRp). Here we show the synthesis of Cordycepin and 2'-O-methyl alpha-P-borano triphosphate via a one-pot phosphorochloridite synthesis under mild conditions. These analogues will be used for future structure-activity relationship (SAR) studies.
Cheek
Marcus A
MA
Department of Chemistry, Duke Universty, BOX 90346, Durham, NC 27708, USA.
Dobrikov
Mikhail I
MI
Wennefors
Charlotta K
CK
Xu
Zhihong
Z
Hashmi
Syed Nadeem
SN
Shen
Xiaoying
X
Shaw
Barbara Ramsay
BR
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D016174:Hepacivirus / Q000201:enzymology; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors; D013942:Thymine Nucleotides / Q000138:chemical synthesis / Q000737:chemistry
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D001896:Boron Compounds; D013942:Thymine Nucleotides; D000255:Adenosine Triphosphate; D012324:RNA-Dependent RNA Polymerase