Convergent Synthesis and Anti‐Pancreatic Cancer Cell Growth Activity of a Highly Branched Heptadecasaccharide from Carthamus tinctorius. (4th July 2022)

• Record Type: Journal Article
• Authors: Hu, Chaoyu; Wu, Shengjie; He, Fei; Cai, Deqin; Xu, Zhuojia; Ma, Wenjing; Liu, Yating; Wei, Bangguo; Li, Tiehai; Ding, Kan
• Is Part Of: Angewandte Chemie. Volume 134:Number 32(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-07-04
• Subjects: Antitumor Agents -- Carbohydrates -- Glycosylation -- Oligosaccharides -- Total Synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202202554
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Bioactive polysaccharides from natural resources target various biological processes and are increasingly used as potential target molecules for drug development. However, the accessibility of branched and long complex polysaccharide active domains with well‐defined structures remains a major challenge. Herein we describe an efficient first total synthesis of a highly branched heptadecasaccharide moiety of the native bioactive galectin‐3‐targeting polysaccharide from Carthamus tinctorius L. as well as shorter fragments of the heptadecasaccharide. The key feature of the approach is that a photo‐assisted convergent [6+4+7] one‐pot coupling strategy enables rapid assembly of the heptadecasaccharide, whereby a photoremovable o ‐nitrobenzyl protecting group is used to generate the corresponding acceptor for glycosylation in situ upon ultraviolet radiation. Biological activity tests suggest that the heptadecasaccharide can target galectin‐3 and inhibit pancreatic cancer cell growth. Abstract : The first total synthesis of a highly branched heptadecasaccharide moiety of the native bioactive galectin‐3‐targeting polysaccharide from Carthamus tinctorius has been accomplished via a photo‐assisted convergent [6+4+7] one‐pot coupling strategy. This work demonstrates a representative example to explore potential active domains of the polysaccharide for structure–activity relationship studies, thereby facilitating pharmaceutical development.