Collect. Czech. Chem. Commun. 2000, 65, 1713-1725

Synthesis of Acyclic Nucleotide Analogues Derived from N3-Substituted Isoguanine

Petr Alexander*, Antonín Holý, Miloš Buděšínský and Milena Masojídková

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic


Reaction of 9-benzyl-6-{[(dimethylamino)methylidene]amino}purin-2(3H)-one (7) with ethylene carbonate gave a mixture of 9-benzyl-2-(2-hydroxyethoxy)purin-6-amine (10) and 2-amino-9-benzyl-3-(2-hydroxyethyl)purin-2(3H)-one (11). This mixture reacted with diisopropyl (tosyloxymethyl)phosphonate in the presence of NaH followed by catalytic hydrogenation and bromotrimethylsilane treatment to afford isomeric 6-amino-3-[2-(phosphonomethoxy)ethyl]purin-2(3H)-one (3) and 2-[2-(phosphonomethoxy)ethoxy]purin- 6-amine (15). Similar treatment of compound 7 with tritylglycidol gave two isomeric 2-hydroxy-3-(trityloxy)propyl derivatives 18, 20 which were subsequently condensed with diisopropyl (tosyloxymethyl)phosphonate to afford protected diester intermediates 21 and 22; these compounds were transformed by hydrogenolysis and ester cleavage with bromotrimethylsilane to the isomeric 6-amino-3-[3-hydroxy-2-(phosphonomethoxy)propyl]- purin-2(3H)-one (2) and 2-[3-hydroxy-2-(phosphonomethoxy)propoxy]purin-6-amine (24). None of the free phosphonates 2, 3, 15 or 24 exhibited any antiviral or cytostatic activity.

Keywords: Purines; Nucleosides; Nucleotides; Acyclic analogs; Phosphonates; Alkylation; Antivirals.

References: 55 live references.