Synthesis 2013; 45(2): 272-280
DOI: 10.1055/s-0032-1317782
paper
© Georg Thieme Verlag Stuttgart · New York

Chemo-Enzymatic Synthesis and Biological Evaluation of 5,6-Disubstituted Benzimidazole Ribo- and 2′-Deoxyribonucleosides

Authors

  • Irina D. Konstantinova

    a   Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 GSP, Moscow B-437, Russian Federation
  • Olga M. Selezneva

    a   Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 GSP, Moscow B-437, Russian Federation
  • Ilja V. Fateev

    a   Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 GSP, Moscow B-437, Russian Federation
  • Tamara A. Balashova

    a   Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 GSP, Moscow B-437, Russian Federation
  • Svetlana K. Kotovskaya

    b   I. Ya. Postovsky Institute of Organic Synthesis, the Ural Branch of the Russian Academy of Sciences, Sophia Kovalevskaya/Academicheskaya St. 22/20, 620041 Yekaterinburg, Russian Federation
  • Zoya M. Baskakova

    b   I. Ya. Postovsky Institute of Organic Synthesis, the Ural Branch of the Russian Academy of Sciences, Sophia Kovalevskaya/Academicheskaya St. 22/20, 620041 Yekaterinburg, Russian Federation
  • Valery N. Charushin

    b   I. Ya. Postovsky Institute of Organic Synthesis, the Ural Branch of the Russian Academy of Sciences, Sophia Kovalevskaya/Academicheskaya St. 22/20, 620041 Yekaterinburg, Russian Federation
  • Alexander V. Baranovsky

    c   Institute of Bioorganic Chemistry, National Academy of Sciences, Acad. Kuprevicha 5/2, 220141 Minsk, Belarus   Fax: +375(17)2678761   eMail: imikhailopulo@gmail.com
  • Anatoly I. Miroshnikov

    a   Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 GSP, Moscow B-437, Russian Federation
  • Jan Balzarini*

    d   Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium
  • Igor A. Mikhailopulo*

    c   Institute of Bioorganic Chemistry, National Academy of Sciences, Acad. Kuprevicha 5/2, 220141 Minsk, Belarus   Fax: +375(17)2678761   eMail: imikhailopulo@gmail.com
Weitere Informationen

Publikationsverlauf

Received: 11. Oktober 2012

Accepted after revision: 16. November 2012

Publikationsdatum:
07. Dezember 2012 (online)


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Abstract

A number of new 5,6-disubstituted benzimidazoles have been prepared and their substrate properties for recombinant E. coli purine nucleoside phosphorylase (PNP; the product of the deoD gene) in the transglycosylation reaction were investigated. The heterocyclic­ bases showed good substrate activity for PNP and the ribo- and 2′-deoxyribonucleosides were synthesized. The predominant (OMe and OEt) or exclusive (Oi-Pr, morpholino, and N-methylpiperazino) formation of the 5-substituted 6-fluoro-1-(β-d-ribofuranosyl)benzimidazoles was observed. The formation of the regioisomeric 6- methoxy-, 6-ethoxy-, or 6-isopropoxy-substituted 1-(2-deoxy-β-d-ribofuranosyl)-5-fluorobenzimidazoles was observed in the trans-2-deoxyribosylation reaction of the corresponding bases. The predominant or exclusive formation of the regioisomeric N 1-nucleosides with bulky 5-substituents of 6-fluorobenzimidazole points to a large hydrophobic pocket in the E. coli PNP active site that can accommodate these groups. The biological activity of the synthesized nucleosides was studied and revealed no inhibitory activity against a broad variety of DNA and RNA viruses. The compounds also lacked significant cytotoxicity.