Collect. Czech. Chem. Commun. 2001, 66, 500-506

An Alternative Synthesis of HPMPC and HPMPA Diphosphoryl Derivatives

Miroslav Otmar*, Milena Masojídková, Ivan Votruba and Antonín Holý

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic


In (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC) and (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine (HPMPA) with 3-hydroxy functions protected with 4,4'-dimethoxytrityl (DMTr) groups, phosphonate groups were transformed to the morpholides and treated with bis(tributylammonium) diphosphate. Selective cleavage of the DMTr group in the presence of the labile diphosphate residue was achieved in water at pH 2.5. Purification by charcoal adsorption followed by anion exchange chromatography afforded phosphonate-diphosphate compounds (HPMPCpp, HPMPApp).

Keywords: Acyclic nucleotide analogs; Nucleotides; HPMPCpp; HPMPApp; Triphosphates; Diphosphates; Phosphonates; Phosphorylation.

References: 16 live references.