Precision Synthesis and Antiliver Fibrosis Activity of a Highly Branched Acidic 63-Mer Pectin Polysaccharide

Abstract

Natural polysaccharides possess various biological functions and have become increasingly important as drug candidates for biomedical development. However, the accessibility to multiple-branched and large-sized acidic polysaccharides with well-defined structures and the identification of related active glycan domains remain challenging. Here, we report the precision synthesis of a highly branched acidic pectin polysaccharide up to a 63-mer containing 10 different glycosidic linkages from Lycium barbarum. The synthetic strategy relies on highly stereoselective modular assembly of an orthogonally protected decasaccharide backbone, efficient synthesis of three side chain glycans by the integration of stereocontrolled one-pot chemoselective glycosylations and a hydrogen-bond-mediated aglycone delivery approach, and convergent assembly of the target polysaccharide in a branched site-specific glycosylation manner via flexible orthogonal protecting group manipulations. Structure–activity relationship studies of synthetic polysaccharide 63-mer and its short fragments (9-mer, 10-mer, 11-mer, and 33-mer) suggest that the decasaccharide as an active glycan domain exhibits better antiliver fibrosis activity.