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Synthesis of Azido and Triazolyl Purine Ribonucleosides
Author(s) -
Līpiņš Dāgs Dāvis,
Jeminejs Andris,
Novosjolova Irina,
Bizdēna Ērika,
Turks Māris
Publication year - 2021
Publication title -
current protocols
Language(s) - English
Resource type - Journals
ISSN - 2691-1299
DOI - 10.1002/cpz1.241
Subject(s) - chemistry , ribonucleoside , purine , stereochemistry , moiety , nucleophile , thio , nucleic acid , organic chemistry , rna , biochemistry , enzyme , catalysis , gene
Here, we describe detailed synthetic protocols for preparation of 6‐amino/thio‐2‐triazolylpurine ribonucleosides. First, 9‐(2′,3′,5′‐tri‐ O ‐acetyl‐β‐ D ‐ribofuranosyl)‐2,6‐diazido‐9 H ‐purine, to be used as a key starting material, is synthesized in an S N Ar reaction with NaN 3 starting from commercially available 9‐(2′,3′,5′‐tri‐ O ‐acetyl‐β‐ D ‐ribofuranosyl)‐2,6‐dichloro‐9 H ‐purine. Next, 2,6‐bis‐triazolylpurine ribonucleoside is obtained in a CuAAC reaction between diazidopurine derivative and phenyl acetylene, and used in S N Ar reactions with N ‐ and S ‐nucleophiles. In these reactions, the triazolyl ring at the purine C6 position acts as a good leaving group. Cleavage of acetyl protecting groups from the ribosyl moiety is achieved in presence of piperidine. In the S N Ar reaction with amino acid derivatives, the acetyl groups remain intact. Moreover, 9‐(2′,3′,5′‐tri ‐O ‐acetyl‐β‐ D ‐ribofuranosyl)‐2,6‐diazido‐9 H ‐purine is selectively reduced at the C6 position using a CuSO 4 ·5H 2 O/sodium ascorbate system. This provides a straightforward approach for synthesis of 9‐(2′,3′,5′‐tri ‐O ‐acetyl‐β‐ D ‐ribofuranosyl)‐6‐amino‐2‐azido‐9 H ‐purine. © 2021 Wiley Periodicals LLC Basic Protocol 1 : Synthesis of 6‐amino‐2‐triazolylpurine ribonucleosides Basic Protocol 2 : Synthesis of 6‐thio‐2‐triazolylpurine ribonucleosides Basic Protocol 3 : Synthesis of 6‐amino‐2‐azidopurine ribonucleoside