Synthesis and Biological Studies of O3‐Aryl Galactosides as Galectin Inhibitors

Abstract

Abstractβ‐Galactose derivatives have recently been reported to selectively inhibit galectin‐3, and a library of O3‐arylated galactosides with varying substitution patterns was designed to study such inhibitions further. The O3‐arylated galactosides were synthesized using diaryliodonium salts under mild and transition metal free conditions, providing the target products in moderate to good yields. An O3‐trifluoroethylated galactoside was also synthesized using iodonium salt chemistry. Azido‐substituted products were subsequently transformed into the corresponding triazoles. After deprotection, a selection of galactoside derivatives were evaluated for inhibitory potencies against galectins‐1, 3, 4 N (N‐terminal domain), 4 C (C‐terminal domain), 7, 8 N, 8 C, 9 N, and 9 C and one compound with promising affinity and selectivity for both the N‐ and C‐terminal domain of galectin‐9 was discovered.