Synthetic Strategies for Bioactive Oligosaccharides

Carbohydrates are essential constituents of numerous biological systems, playing key roles in fundamental processes such as cellular recognition and immunological responses, while also offering significant potential in medical diagnostics and pharmaceutical development. However, the structural complexity of naturally occurring carbohydrates-characterized by heterogeneous glycosylation patterns and diverse branching architectures-poses considerable challenges in the isolation and preparation of homogeneous oligosaccharide samples. Recent advances in synthetic chemistry have led to substantial progress in carbohydrate synthesis, with modern glycosylation methodologies achieving improved stereochemical control and enhanced reaction efficiency, thereby enabling the precise and programmable construction of biologically relevant oligosaccharides. This review provides a systematic evaluation of six major strategies for oligosaccharide assembly: One-pot synthesis strategy, orthoganal protection strategy, preactivation strategy, linear and convergent block strategy, programmable one-pot synthesis strategy, and solid-phase synthesis strategy. For each strategy, we examine the key technological innovations, representative applications, and current limitations. Furthermore, the review discusses emerging trends in the field, emphasizing the transformative role of intelligent automation and machine learning in accelerating the discovery and synthesis of complex carbohydrates.