Synthesis of Azanucleosides by Anodic Oxidation in a Lithium Perchlorate–Nitroalkane Medium and Diversification at the 4′‐Nitrogen Position

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...

Full description

Saved in:
Bibliographic Details
Published in:Angewandte Chemie International Edition 2017-03, Vol.56 (14), p.4011-4014
Main Authors: Shoji, Takao, Kim, Shokaku, Chiba, Kazuhiro
Format: Article
Language:English
Subjects:
Alkanes
Anodizing
Anticancer properties
C−H activation
Electrochemistry
Fluorescent dyes
Fluorescent indicators
glycosidation
Hydrogen bonds
Lipophilic
Lithium
Lithium perchlorates
Metathesis
Nitrogen
Nitromethane
Nuclease
nucleoside analogues
Oxidation
Perchlorate
Perchloric acid
postmodification
Structure-function relationships
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Celebrating diversity: Azanucleosides with an acryloyl group on the 4′‐N atom were prepared by anodic oxidation in a lithium perchlorate–nitroalkane solution, whereby the use of nitroethane rather than nitromethane lowered the oxidation potential of the N‐acryloyl prolinol considerably. The resulting azanucleosides could be functionalized at the acryloyl group with a liphophilic alkanethiol or a fluorescent dye in a subsequent step.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201700547