Utilization of 1,3-Dioxolanes in the Synthesis of alpha-branched Alkyl and Aryl 9-[2-(Phosphonomethoxy)Ethyl]Purines and Study of the Influence of alpha-branched Substitution for Potential Biological Activity

0504619 - ÚOCHB 2020 RIV US eng J - Článek v odborném periodiku
Pomeisl, Karel - Pohl, Radek - Snoeck, R. - Andrei, G. - Krečmerová, Marcela
Utilization of 1,3-Dioxolanes in the Synthesis of alpha-branched Alkyl and Aryl 9-[2-(Phosphonomethoxy)Ethyl]Purines and Study of the Influence of alpha-branched Substitution for Potential Biological Activity.
Nucleosides Nucleotides & Nucleic Acids. Roč. 38, č. 2 (2019), s. 119-156. ISSN 1525-7770. E-ISSN 1532-2335
Grant CEP: GA ČR(CZ) GA14-00522S
Institucionální podpora: RVO:61388963
Klíčová slova: acyclic nucleoside phosphonates * PMEG * PEEG * 1,3-dioxolanes * dialkyl phosphite * trialkyl phosphite
Obor OECD: Organic chemistry
Impakt faktor: 1.556, rok: 2019
Způsob publikování: Omezený přístup
https://www.tandfonline.com/doi/full/10.1080/15257770.2018.1506884

Syntheses of alpha-branched alkyl and aryl substituted 9-[2-(phosphonomethoxy)ethyl]purines from substituted 1,3-dioxolanes have been developed. Key synthetic precursors, alpha-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 alpha-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.
Trvalý link: http://hdl.handle.net/11104/0296206