Synthesis and antiviral activity of novel erythrofuranosyl imidazo[1,2-a]pyridine C-nucleosides constructed via palladium coupling of iodoimidazo[1,2-a]pyridines and dihydrofuran

2,5,6-Trichloro-1-(beta-d-ribofuranosyl)benzimidazole (TCRB) and certain analogues have shown significant activity against human cytomegalovirus. The metabolic instability of the glycosidic linkage in TCRB prompted us to synthesize the structurally similar imidazo[1,2-a]pyridine erythrofuranosyl C-nucleosides. As an approach to the synthesis of polychlorinated imidazo[1,2-a]pyridine C-3-erythrofuranosides, a palladium-based methodology for coupling 2,3-dihydrofuran with chlorinated 3-iodoimidazo[1,2-a]pyridines was developed and optimized to give 80-90% yields of 2,6-dichloro- and 2,6,7-trichloro-3-(2,3-dideoxy-2,3-didehydro-d/l-erythrofuranosyl)imidazo[1,2-a]pyridine. Dihydroxylation of these didehydro derivatives with osmium tetroxide or with AD-mix alpha gave a mixture of erythrofuranosyl C-nucleosides that were separated by standard and then chiral chromatography. When screened for anti-HCMV and HSV-1 activity, the alpha-d anomer of 2,6,7-trichloro-3-(erythrofuranosyl)imidazo[1,2-a]pyridine proved to be the most active member of the series, while the beta-anomers all proved to be inactive.