Collect. Czech. Chem. Commun. 2000, 65, 1357-1373

Synthesis of Acyclic Nucleotide Analogues Derived from 2-Amino-6-C-substituted Purines via Cross-Coupling Reactions of 2-Amino-9-{2-[(diisopropoxyphosphoryl)methoxy]ethyl}-6-halopurines with Diverse Organometallic Reagents

Michal Česnek, Michal Hocek* and Antonín Holý

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


Cross-coupling reactions of 2-amino-6-chloro-9-{2-[(diisopropoxyphosphoryl)methoxy]ethyl}purine (1) and 2-amino-9-{2-[(diisopropoxyphosphoryl)methoxy]ethyl}-6-iodopurine (2) with diverse types of organometallic reagents have been studied. Arylboronic acids reacted with 1 to give the corresponding 2-amino-6-arylpurines 3a-3d in good yields. Analogously, trialkylaluminium reagents were used for the preparation of 6-alkyl-2-aminopurines 3k and 3l from 1. Hetarylzinc halides and hetarylstannanes required the use of 2-amino-6-iodopurine 2 to give the corresponding 2-amino-6-hetarylpurines 3e-3j in fair to good yields. A CuI/KF mediated coupling of perfluoroalkylsilanes with 2 afforded the 2-amino-6-perfluoroalkylpurines 3m and 3n in moderate yields. Cleavage of the esters 3 with bromo(trimethyl)silane gave the target free phosphonates 4 that were purified by ion- exchange chromatography. The title compounds were tested on antiviral and cytostatic activity.

Keywords: Purines; Phosphonates; Cross-coupling reactions; Nucleosides; Nucleotides; Acyclic analogs; Stannanes; Boronic acids; Organozinc reagents; Trialkylaluminum reagents; Perfluoroalkylations; Antivirals.

References: 42 live references.