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Synthesis of Azanucleosides by Anodic Oxidation in a Lithium Perchlorate–Nitroalkane Medium and Diversification at the 4′‐Nitrogen Position
Author(s) -
Shoji Takao,
Kim Shokaku,
Chiba Kazuhiro
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201700547
Subject(s) - nitromethane , chemistry , nitroethane , acryloyl chloride , lithium perchlorate , electrochemistry , nitroaldol reaction , photochemistry , medicinal chemistry , combinatorial chemistry , organic chemistry , catalysis , polymer , electrode , enantioselective synthesis , monomer , acrylate
Azanucleosides, in which the 4′‐oxygen atom has been replaced with a nitrogen atom, have drawn much attention owing to their anticancer and antivirus activity, and tolerance towards nucleases. However, the traditional synthetic strategy requires multiple steps and harsh conditions, thereby limiting the structural and functional diversity of the products. Herein we describe the synthesis of azanucleosides by an electrochemical reaction in a lithium perchlorate–nitroethane medium, followed by postmodification at the 4′‐N position. N ‐Acryloyl prolinol derivatives were converted into azanucleosides by anodic activation of the N ‐α‐C−H bond. Moreover, the use of nitroethane instead of nitromethane lowered the oxidation potential of the N ‐acryloyl prolinols and increased the Faradic yield. The prepared azanucleosides were efficiently functionalized at the 4′‐ N ‐acryloyl group with a lipophilic alkanethiol and a fluorescent dye by conjugate addition and olefin cross‐metathesis, respectively.