Synlett 2012; 23(10): 1541-1545
DOI: 10.1055/s-0031-1290679
letter
© Georg Thieme Verlag Stuttgart · New York

Enzymatic Synthesis of 2′-Deoxy-β-d-ribonucleosides of 8-Azapurines and 8-Aza-7-deazapurines

Vladimir A. Stepchenko
a  Institute of Bioorganic Chemistry, National Academy of Sciences, Acad. Kuprevicha 5/2, 220141 Minsk, Belarus
,
Frank Seela
b  Laboratory of Bioorganic Chemistry and Chemical Biology, Center for Nanotechnology, Heisenbergstr. 11, 48149 Münster, Germany
,
Roman S. Esipov
c  Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 GSP, Moscow B-437, Russian Federation, Fax: +375(17)2678761   Email: imikhailopulo@gmail.com
,
Anatoly I. Miroshnikov
c  Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 GSP, Moscow B-437, Russian Federation, Fax: +375(17)2678761   Email: imikhailopulo@gmail.com
,
Yuri A. Sokolov
a  Institute of Bioorganic Chemistry, National Academy of Sciences, Acad. Kuprevicha 5/2, 220141 Minsk, Belarus
,
Igor A. Mikhailopulo*
a  Institute of Bioorganic Chemistry, National Academy of Sciences, Acad. Kuprevicha 5/2, 220141 Minsk, Belarus
› Author Affiliations
Further Information

Publication History

Received: 30 January 2012

Accepted after revision: 04 April 2012

Publication Date:
29 May 2012 (online)


Abstract

The enzymatic synthesis of 8-azapurine and 8-aza-7-deazapurine 2′-deoxyribonucleosides has been studied. Two methods have been used: (i) transglycosylation employing 2′-deoxyguanosine, 2′-deoxycytidine, 2′-deoxyuridine, and 2′-deoxythymidine as 2-deoxy-d-ribofuranose donors and recombinant E. coli purine nucleoside phosphorylase (PNP) as biocatalyst, and (ii) one-pot synthesis from 2-deoxy-d-ribose and nucleobases employing recombinant E. coli ribokinase (RK), phosphopentomutase (PPM) and PNP as biocatalysts. Good substrate activity was observed for all bases studied except 2-amino-8-aza-6-chloro-7-deazapurine, which afforded the desired N 9-nucleoside in moderate yield due to very low solubility of the base and partial replacement of C6-chloro atom of the base and formed nucleoside with a hydroxy group. The participation of Ser90 Oγ of E. coli PNP in the binding of 8-aza-7-deazapurines in the catalytic center of PNP followed by the formation of a productive complex and glycosidic bond is suggested.

Supporting Information

 
  • References and Notes

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