Stereoselective synthesis of N1-6-methyluridine and related 2-substituted analogues

Coupling reaction of 2-substituted-6-methyl-4(3H)-pyrimidinones (1a,b) with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose (ABR) afforded the corresponding N1-2,6-disubstituted nucleosides (2a,b) without any trace of the N3-isomer. The 2-methylthio-6-methyl derivative (2b) has then proved to be a key intermediate for the synthesis of N1-6-methyluridine (4) and the corresponding N1-2-amino-6-methyl derivative (5), suggesting the possibility to obtain different 2,6-disubstituted derivatives by means of methylthio nucleophilic substitution. A successful solid phase application was also shown. © 2007 The Japan Institute of Heterocyclic Chemistry.