Collect. Czech. Chem. Commun. 2001, 66, 1393-1406

Transformation of 8-[(2-Hydroxyalkyl)sulfanyl]adenines to 6-Amino-7H-purin-8(9H)-one Derivatives

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


Alkylation of 6-amino-7H-purin-8(9H)-thione (8-sulfanyladenine, 1) with one equivalent of (R)-[(trityloxy)methyl]oxirane gave its S-alkyl derivative 2, which was converted to the 6-amino-7H-purin-8(9H)-one (3), while alkylation of 1 with two equivalents of (S)-[(trityloxy)methyl]oxirane afforded a mixture of N3,S-dialkylated product 4a, N9-monoalkyl and N7,N9-dialkyl derivatives of 6-amino-7H-purin-8(9H)-one, 5a and 6a, respectively. This approach can be used for rapid and easy transformation of 8-[(2-hydroxyalkyl)sulfanyl]adenines to the derivatives of 6-amino-7H-purin-8(9H)-one (8-hydroxyadenine) using NaH or Cs2CO3 in DMF. The course of the S→O transformation strictly depends on the character of the starting compounds and on the reaction conditions. N9-Alkyl-8-[(2-hydroxyalkyl)sulfanyl]adenines 10, 12, 14 and 17 were rapidly converted to the corresponding 6-amino-7H-purin-8(9H)-one derivatives 11, 13, 11 and 18, respectively. N9-Unsubstituted 2 reacts slowly, and N3-alkyl derivative 4a is stable under the same reaction conditions. The described transformation does not occur when the hydroxy group in 8-[(2-hydroxyalkyl)sulfanyl]adenine derivative 15 is protected. The reaction using NaH proceeds more rapidly than that using Cs2CO3.

Keywords: Purines; Acyclic nucleoside and nucleotide analogs; Alkylation; Thiols; Thiones; Hydrolysis.

References: 13 live references.