Premium
Synthesis of 2,6‐Dialkyl(aryl)purine Nucleosides by Exploiting the Reactivity of Nebularine N 1‐Oxide towards Grignard Reagents
Author(s) -
D'Errico Stefano,
Oliviero Giorgia,
Borbone Nicola,
Piccialli Vincenzo,
D'Atri Valentina,
Mayol Laura,
Piccialli Gennaro
Publication year - 2013
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201300941
Subject(s) - chemistry , purine , pyrimidine , aromatization , reactivity (psychology) , reagent , aryl , grignard reaction , deoxyribonucleoside , nucleoside , grignard reagent , oxide , combinatorial chemistry , stereochemistry , organic chemistry , enzyme , catalysis , alkyl , medicine , alternative medicine , pathology
The synthesis of 2,6‐dialkyl(aryl)purine nucleosides by application of a double addition of Grignard reagents to N 1‐oxide purine nucleosides is described. The synthetic protocol exploits the reactivity of both the C6–N1–O – and C2–N1–O – moieties of the purine base. The overall process consists of initial Grignard reagent addition to the C6 of nebularine N 1‐oxide followed by aromatization to give a C 6‐substituted nucleoside. Regeneration of the N 1‐oxide is then followed by a second Grignard addition at C2 causing the opening of the pyrimidine ring. Cyclization of the transiently opened pyrimidine is then driven by aromatization of the system to afford the final purine system.