Collect. Czech. Chem. Commun. 2000, 65, 1698-1712

Synthesis of Acyclic Nucleoside and Nucleotide Analogs Derived from 6-Amino-7H-purine-8(9H)-thione and 8-(Methylsulfanyl)adenine

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


Reaction of 8-bromoadenine derivatives 1 with thiourea in ethanol or butanol was used for the synthesis of the corresponding N9-substituted 6-amino-7H-purine-8(9H)-thiones 2. 8-(Methylsulfanyl)adenine derivatives 3 were prepared by reaction of thiones 2 with iodomethane in 1 M sodium methoxide or in aqueous 1.5 M potassium hydroxide. Alkylation of 6-amino-7H-purine-8(9H)-thione (2a) proceeds preferentially on the sulfur atom. Under similar conditions, alkylation of 8-(methylsulfanyl)adenine (3a) with diverse alkylation agents afforded N9-substituted adenine derivatives 3 and 6, and N3-substituted adenine derivatives 5 and 7. 8,3'-S-Anhydro derivatives 9 were prepared in good yields by cyclization of 6-amino-7H-purine-8(9H)-thiones 2d and 2f under the Mitsunobu reaction conditions.

Keywords: Purines; Acyclic nucleoside and nucleotide analogues; Nucleosides; Nucleotides; Alkylation; Mitsunobu reaction; Anhydro derivatives; Cyclization.

References: 41 live references.