Synthesis and Structural Revision of a Natural Tetrasaccharide from Starfish Asterias rollestoni Bell

Abstract Starfish provide important saponins with diverse bioactivities as the secondary metabolites, among which 2‐ O ‐glycosylated glycosides are commonly found. Preparation of those 1,2‐ trans 2‐ O ‐glycosylated glycosides usually relies on 2‐ O ‐acyl participation requiring the selective installation and cleavage of 2‐ O ‐acyl groups. A convergent synthesis using 2‐ O ‐glycosylated oligosaccharide donors would be more straightforward but also pose greater challenges. Herein, we report a convergent synthesis of a distinctive tetrasaccharide isolated from starfish Asterias rollestoni Bell. Dual 2‐(diphenylphosphinoyl)acetyl (DPPA) groups at O3 and O4 on galactose moiety led to high β‐selectivities (β/α=12/1 or β only) in the challenging [2+2] glycosylation, giving the desired tetrasaccharides in >90 % yields from the 2‐ O ‐glycosylated disaccharide donors. These synthetic studies have also unambiguously revised the structure of these natural tetrasaccharides. This work would facilitate further studies on new inhibitors of α‐glucosidase as hypoglycemic drugs.