Semisynthesis of Chondroitin Sulfate E Tetrasaccharide from Hyaluronic Acid.

Chondroitin sulfate (CS) is crucial glycosaminoglycan that regulates key functions of the nervous system. CS-E is one of the key CS subtypes that modulates the biological function of CS. Herein, N-protecting-group-free semisynthesis of CS-E tetrasaccharide is reported using hyaluronic acid as a readily available starting material. The synthetic process utilizes the enzymatic degradation and selective C4 hydroxyl group conversion as key approaches for direct construction of the CS tetrasaccharide precursor, which furnishes the neuroactive CS-E tetrasaccharide in 15 steps.