title: Efficient synthesis of 2,9-disubstituted 8-hydroxyadenine derivatives.
abstract: An efficient and general method for the synthesis of 2,9-disubstituted 8-hydroxyadenines, which are expected to have various biological activities, was realized. 5-Amino-4-cyano-2-hydroxyimidazoles(1) were prepared from aminomalononitrile and isocyanates as key intermediates. The condensation of 1a with amidines, imidates, guanidine, urea and thioureas afforded 8-hydroxyadenines (2-6) possessing various substituents at the 2-position. Furthermore, selective alkylation of 2-amino- and 2-hydroxyadenines (4 and 6) successively proceeded to give the corresponding 2-alkylamino- and 2-alkoxyadenines (5 and 7), respectively. 2-Alkylthioadenines (15) were prepared by an analogous reaction of 1a with benzoyl isothiocyanate and subsequent S-alkylation. The imidazoles 1 are most useful intermediates for the synthesis of 8-hydroxyadenine derivatives.
authors.affiliation: Laboratory of Medicinal Chemistry, Gifu Pharmaceutical University, Mitahora-higashi, Gifu 502-8585, Japan. hirota@gifu-pu.ac.jp
authors.forename: Kosaku
authors.initials: K
authors.lastname: Hirota
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kazaoka
authors.forename: Itaru
authors.initials: I
authors.lastname: Niimoto
authors.forename: Hironao
authors.initials: H
authors.lastname: Sajiki