An efficient synthesis of acyclic N7- and N9-adenine nucleosides via alkylation with secondary carbon electrophiles to introduce versatile functional groups at the C-1 position of acyclic moiety

Nucleosides Nucleotides Nucleic Acids. 2006;25(2):121-40. doi: 10.1080/15257770500446816.

Abstract

The introduction of versatile functional groups, allyl and ester, at the C-1 position of the acyclic chain in acyclic adenine nucleosides was achieved for the first time directly by alkylation of adenine and N6-potected adenine. Thus, the C-1'-substituted N9-adenine acyclic nucleoside, adenine-9-yl-pent-4-enoic acid ethyl ester (11), was prepared by direct alkylation of adenine with 2-bromopent-4-enoic acid ethyl ester (6), while the corresponding N7-regioisomer, 2-[6-(dimethylaminomethyleneamino)-purin-7-yl]-pent-4-enoic acid ethyl ester (10), was obtained in one step by the coupling of N, N-dimethyl-N'- (9H-purin-6-yl)-formamidine (9) with 2-bromopent-4-enoic acid ethyl ester (6). The functional groups, ester and allyl, were converted to the desired hydroxymethyl and hydroxyethyl groups, and subsequently to phosphonomethyl derivatives and corresponding pyrophosphorylphosphonates.

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / chemical synthesis*
  • Adenine / chemistry
  • Alkylation
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / pharmacology
  • Carbon / chemistry*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Nucleosides / chemical synthesis*
  • Nucleosides / chemistry

Substances

  • Antiviral Agents
  • Nucleosides
  • Carbon
  • Adenine