Synthesis of glycosaminoglycans via enzymatic polymerization

Hyaluronic acid and chondroitin were successfully synthesized as representative molecules of glucosaminoglycans and galactosaminoglycans found in a glycosaminoglycan family via enzymatic polymerization catalyzed by testicular hyaluronidases. A newly designed N‐acetylhyalobiuronate oxazoline derivative with a β‐D‐glucuronyl‐(1→3)‐N‐acetyl‐D‐glucosamine disaccharide structure served as a transition‐state analogue substrate monomer for the enzyme, giving rise to artificial hyaluronic acid in 52% yields with a number‐average molecular weight of 1.35 × 104 through ring‐opening polyaddition in a perfect regioselective and stereoselective manner. A novel N‐acetylchondrosine oxazoline derivative with a β‐D‐glucuronyl‐(1→3)‐N‐acetyl‐D‐galactosamine disaccharide structure also acted as a transition‐state analogue substrate monomer for the enzyme, yielding artificial chondroitin in 35% yields with a number‐average molecular weight of 2.5 × 103. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3541–3548, 2003 Hyaluronic acid and chondroitin were successfully synthesized via enzymatic polymerization catalyzed by testicular hyaluronidases. A newly designed N‐acetylhyalobiuronate oxazoline derivative (1) served as a transition‐state analogue substrate monomer for the enzyme, giving rise to artificial hyaluronic acid in 52% yields with a number‐average molecular weight of 1.35 × 104 through ring‐opening polyaddition in a perfect regioselective and stereoselective manner. A novel N‐acetylchondrosine oxazoline derivative (2) also acted as a transition‐state analogue substrate monomer for the enzyme, yielding artificial chondroitin in 35% yields with a number‐average molecular weight of 2.5 × 103.