Utilization of 1,3-Dioxolanes in the Synthesis of α-branched Alkyl and Aryl 9-[2-(Phosphonomethoxy)Ethyl]Purines and Study of the Influence of α-branched Substitution for Potential Biological Activity
Language English Country United States Media print-electronic
Document type Journal Article
- Keywords
- 1,3-dioxolanes, Acyclic nucleoside phosphonates, PEEG, PMEG, dialkyl phosphite, trialkyl phosphite,
- MeSH
- Antiparasitic Agents chemical synthesis chemistry pharmacology MeSH
- Antiviral Agents chemical synthesis chemistry pharmacology MeSH
- Dioxolanes chemistry MeSH
- DNA Viruses drug effects MeSH
- Enzyme Inhibitors chemical synthesis chemistry pharmacology MeSH
- Humans MeSH
- Microbial Sensitivity Tests MeSH
- Molecular Structure MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Pentosyltransferases antagonists & inhibitors metabolism MeSH
- Plasmodium falciparum drug effects enzymology MeSH
- Purines chemical synthesis chemistry pharmacology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Antiparasitic Agents MeSH
- Antiviral Agents MeSH
- Dioxolanes MeSH
- hypoxanthine-guanine-xanthine phosphoribosyltransferase MeSH Browser
- Enzyme Inhibitors MeSH
- Pentosyltransferases MeSH
- Purines MeSH
Syntheses of α-branched alkyl and aryl substituted 9-[2-(phosphonomethoxy)ethyl]purines from substituted 1,3-dioxolanes have been developed. Key synthetic precursors, α-substituted dialkyl [(2-hydroxyethoxy)methyl]phosphonates were prepared via Lewis acid mediated cleavage of 1,3-dioxolanes followed by reaction with dialkyl or trialkyl phosphites. The best preparative yields were achieved under conditions utilizing tin tetrachloride as Lewis acid and triisopropyl phosphite. Attachment of purine bases to dialkyl [(2-hydroxyethoxy)methyl]phosphonates was performed by Mitsunobu reaction. Final α-branched 9-[2-(phosphonomethoxy)ethyl]purines were tested for antiviral, cytostatic and antiparasitic activity, the latter one determined as inhibitory activity towards Plasmodium falciparum enzyme hypoxanthine-guanine-xanthine phosphoribosyltransfesase. In most cases biological activity was only marginal.
b Institute of Physics Czech Academy of Sciences Prague Czech Republic
c Rega Institute for Medical Research Katholieke Universiteit Leuven Belgium
Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Prague Czech Republic
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