Semisynthesis of Chondroitin Sulfate E Tetrasaccharide from Hyaluronic Acid

Abstract

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.

Programmable one cycle–one disaccharide unit modular synthesis of hyaluronan and chondroitin hybrid glycans

“…We first tested the activity of glycosyltransferases (GNT and PmCS) toward UDP-GlcN or UDP-GalN using HA tetrasaccharide 1 as starting substrate. [23][24][25] Unfortunately, neither of those sugar donors can be recognized by GNT or PmCS (Table 1).…”

A Review of Chondroitin Sulfate’s Preparation, Properties, Functions, and Applications

“…Recently, fucosylated CS or its oligosaccharides were reported to be synthesized via chemical synthesis [75][76][77]. CS and its subtypes can also be synthesized using semisynthesis or total synthesis methods [78][79][80][81]. Interestingly, except for the pure chemical or enzymatic processes, the combination of these two methods, chemoenzymatic synthesis, has received a great deal of attention recently.…”

Semisynthesis of Chondroitin Sulfate Oligosaccharides Based on the Enzymatic Degradation of Chondroitin

“…Despite recent advances in the synthesis of CS oligosaccharides, , the extremely long routes, low yields, and small scale limit the supply of enough pure CS materials for biological research, which stagnates current studies at the tetrasaccharide level, so the development of new synthetic strategies for CS oligomers, especially for the hexamer and longer sequences, is of great importance but still challenging. To reduce protecting-group manipulations and the iterative glycosylation steps, our research group has recently reported the semisynthesis of CS-E tetrasaccharide from hyaluronan with enzymatic degradation and C4 hydroxyl group conversion as the key steps (Scheme ).…”