Synthesis of 3-azido-2,4,6-tri-O-(4-methoxybenzyl)-3-deoxy-galactopyranoside

Abstract: Galectin-3 is a protein that is involved in many physiological processes such as metastasis, T-cell regulation etc. which makes it a good drug target for the medicinal chemist. In a paper made by Doak ete al (2015) macrocyclization emerged as an interesting strategy for new drug design as macrocycles remained orally active in chemical space previously thought of as “unsuitable” as per the classical rules defined by Lipinsky. Previous work done in the Nilsson group at Lund university has explored the binding event of monosaccharide galectin-3 inhibitors based on a galactose scaffold. Based on X-ray crystallography obtained from previous work we predicted that a macrocyclic structure would retain much of the same configuration in the binding pocket as the monosaccharides. By comparing the open and cyclised compounds we expect to obtain valuable thermodynamic data of the binding event to aid future drug design. With this goal in mind 3-azido-2,4,6-tri-O-(4-methoxybenzyl)-3-deoxy-galactopyranoside was synthesized and a strategy to obtain the macrocycle has been proposed in this paper.