Enzymatic precision polymerization for synthesis of glycosaminoglycans and their derivatives

Hyaluronidase (HAase)-catalyzed polymerization was performed to provide synthetic hyaluronan (HA), chondroitin (Ch) and their derivatives. The 2-methyl oxazoline derivatives derived from their repeating disaccharides of N-acetylhyalobiuronate (1a) and N-acetylchondrosine (3a) were effectively polymerized by the enzyme, giving rise to synthetic HA and synthetic Ch in good yields through regio-selective and stereo-controlled ring-opening polyaddition. The oxazoline derivatives of 2-ethyl (1b, 3b), 2-n-propyl (1c, 3c), 2-isopropyl (1d, 3d), 2-phenyl (1e, 3e), 2-vinyl (1f, 3f) and 2-isopropenyl (1g) were synthesized and subjected to the enzymatic reaction. Monomers 1b, 1c, 1f, 3b and 3f were polymerized to corresponding polysaccharides 2b, 2e, 2f, 4b and 4f, all of which are unnatural glycosaminoglycans. Compounds 1d, 3e and 3d were also catalyzed by the enzyme, affording oligomers of 2d, 4c and 4d were produced in trace amounts. Monomers 1e, 1g and 3e were not catalyzed by HAase.