Collection of Czechoslovak Chemical Communications - digital archive 

Abstract

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.