2-amino-8-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)imidazo[1,2-a]-1,3 ,5-triazin-4(8H)-one: Synthesis and conformation of a 5-aza-7-deazaguanine fluoronucleoside

Abstract

Nucleobase-anion glycosylation of 2-[(2-methyl-1-oxopropyl)amino]imidazo[1,2-a]-1,3,5-triazin-4(8H)one (6) with 3 5-di-O-benzoyl-2-deoxy-2-fluoro-alpha-D-arabinofuranosyl bromide (8) furnishes a mixture of the benzoyl-protected anomeric 2-amino-8-(2-deoxy-2-fluoro-D-arabinofuranosyl)imidazo[1,2-a]-1 3,5-triazin4(8H)-ones 9/10 in a ratio of ca. 1:1. After deprotection, the inseparable anomeric mixture 3/4 was silylated. The obtained 5-O-[(1,1-dimethylethyl)diphenylsilyl] derivatives 11 and 12 were separated and desilylated affording the nucleoside 3 and its alpha-D anomer 4. Similar to 2'-deoxy-2'-fluoroarabinoguanosine, the conformation of the sugar moiety is shifted from S towards N by the fluoro substituent in arabino configuration.