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Synthesis of Ribo‐Azanucleosides by Anodic Oxidation: Reactivity Control of Intermediate for Efficient Access to Pharmacophores
Author(s) -
Okamoto Kazuhiro,
Shoji Takao,
Tsutsui Mizuki,
Shida Naoki,
Chiba Kazuhiro
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201804285
Subject(s) - chemistry , reactivity (psychology) , combinatorial chemistry , pharmacophore , iminium , lithium perchlorate , substituent , anomer , perchlorate , stereoselectivity , lithium (medication) , electrochemistry , nucleobase , stereochemistry , organic chemistry , dna , catalysis , medicine , ion , biochemistry , alternative medicine , electrode , pathology , endocrinology
Azanucleosides, the sugar‐modified nucleoside analogues, have various biological activities, while their efficient synthetic strategy is still under development. Herein, a novel method for the synthesis of pharmaceutically relevant azanucleosides, β‐anomers of ribo‐azanucleosides, by means of site‐specific anodic C−H activation by using a nitroalkane–lithium perchlorate medium is reported. A mechanistic study of the electrochemical reaction and the armed/disarmed concept from traditional glycochemistry revealed that the 2′‐substituent has a significant effect on the reactivity of prolinol derivative, and suitable carboxylic acid additives can control the reactivity of the intermediate species, an iminium cation equivalent. Finally, this method was demonstrated to be applicable for the synthesis of β‐anomers of ribo‐azanucleosides with all four nucleobases in a stereoselective manner.