Michael De Castro

A series of 2-deoxy-2-iodo-α-d-mannopyranosylbenzotriazoles was synthesized using the benzyl, 4,6-benzylidene and acetyl protected D-glucal in the presence of N-iodosuccinimide (NIS). Subsequent removal of the iodine at the C-2 position using tributyltin hydride under free radical conditions afforded the 2-deoxy-α-d-glucopyranosylbenzotriazoles in moderate to high yields. This method was extended to the preparation of substituted 2-deoxy-β-d-glucopyranosylimidazoles as well. The stereoselectivity of the addition reaction and the effect of the protecting group and temperature on anomer distribution of the benzotriazole series were also investigated. The anticancer properties of the newly synthesized compounds were evaluated in a series of viability studies using HeLa (human cervical adenocarcinoma), human breast and lung cancer cell lines. The N-[3,4,6-tri-O-benzyl-2-deoxy-α-d-glucopyranosyl]-1H-benzotriazole and the N-[3,4,6-tri-O-acetyl-2-deoxy-α-d-glucopyranosyl]-2H-benzotriazole were found to be the most potent cancer cell inhibitors at 20 µM concentrations across all four cell lines.

We herein report the synthesis of 2‐deoxy‐2‐iodo‐glycosylamides, glycosylurea, N‐glycosylbenzotriazole, and N‐glycosyl imidazole by addition reaction of trimethylsilyl amides, imidazoles, and benzotriazoles to D‐glucal in the presence of N‐iodosuccinimide and propionitrile at 0 °C. Two diastereomers were isolated ― the α‐mannose and β‐gluco isomers. Reduction and substitution reaction of the iodine at position C‐2 led to formation of various 2‐deoxy‐N‐glycosides and 2‐hydroxy‐β‐D‐glucopyranosylamide. The newly generated compounds were screened for their inhibitory activity against various enzymes that included Nav1.7 sodium ion voltage‐gated channel in HEK293 cells and the results are discussed.