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
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články
- Klíčová slova
- 1,3-dioxolanes, Acyclic nucleoside phosphonates, PEEG, PMEG, dialkyl phosphite, trialkyl phosphite,
- MeSH
- antiparazitární látky chemická syntéza chemie farmakologie MeSH
- antivirové látky chemická syntéza chemie farmakologie MeSH
- dioxolany chemie MeSH
- DNA viry účinky léků MeSH
- inhibitory enzymů chemická syntéza chemie farmakologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- pentosyltransferasy antagonisté a inhibitory metabolismus MeSH
- Plasmodium falciparum účinky léků enzymologie MeSH
- puriny chemická syntéza chemie farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antiparazitární látky MeSH
- antivirové látky MeSH
- dioxolany MeSH
- hypoxanthine-guanine-xanthine phosphoribosyltransferase MeSH Prohlížeč
- inhibitory enzymů MeSH
- pentosyltransferasy MeSH
- puriny 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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