Collect. Czech. Chem. Commun. 2001, 66, 517-532

Synthesis of 8-Amino- and N-Substituted 8-Aminoadenine Derivatives of Acyclic Nucleoside and Nucleotide Analogs

Zlatko Janeba*, Antonín Holý and Milena Masojídková

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


8-Aminoadenine derivatives 2 were obtained from 8-bromoadenines 1 in one-pot reaction via 8-azidoadenines. Reaction of 8-bromoadenines 1 with methylamine or dimethylamine in ethanol afforded the corresponding N9-substituted 8-(methylamino)adenines 3 and 8-(dimethylamino)adenines 4. Alkylation of 8-aminoadenine (2a) with diverse alkylation agents afforded N9-substituted 8-aminoadenine derivatives 2, and alkylation of 8-(dimethylamino)adenine (4a) gave mixtures of the corresponding N9-substituted 8-(dimethylamino)adenines 4 and their N3-substituted regioisomers 5. 8,3'-N-Anhydro derivatives 7 were prepared by tosylation of (S)-8-bromo-9-{2-[(diisopropoxyphosphoryl)- methoxy]-3-hydroxypropyl}adenine (1c) followed by treatment with methanolic ammonia or methylamine solution.

Keywords: Purines; Acyclic nucleotide analogues; Amines; Alkylation; N-Cyclonucleosides; Nucleosides; Antivirals.

References: 29 live references.