Bottom-up synthesis of hyaluronan and its derivatives via enzymatic polymerization: direct incorporation of an amido functional group.
This paper reports the synthesis of hyaluronan (HA) and its derivatives via the hyaluronidase-catalyzed polymerization of 2-substituted oxazoline derivative monomers designed as "transition-state analogue substrates". Polymerization of 2-methyl oxazoline monomer from N-acetylhyalobiuronate (GlcAbeta(1-->3)GlcNAc) effectively proceeded at pH 7.5 and 30 degrees C, giving rise to synthetic HA (natural type) in an optimal yield of 78% via ring-opening polyaddition under total control of regioselectivity and stereochemistry. Hyaluronidase catalysis enabled the polymerization of 2-ethyl, 2-n-propyl, and 2-vinyl monomers, affording the corresponding HA derivatives (unnatural type) with N-propionyl, N-butyryl, and N-acryloyl functional groups, respectively, at the C2 position of all glucosamine units in good yields. The 2-isopropyl oxazoline derivative provided the N-isobutyryl derivative of HA in low yields. Monomers of 2-phenyl and 2-isopropenyl oxazoline derivatives were not polymerized. The mechanism of the polymerization is discussed.
Ochiai
Hirofumi
H
Department of Materials Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan.
Ohmae
Masashi
M
Mori
Tomonori
T
Kobayashi
Shiro
S
D000577:Amides; D032701:Biomimetics; D002384:Catalysis; D006820:Hyaluronic Acid / Q000138:chemical synthesis*; D006821:Hyaluronoglucosaminidase / Q000378:metabolism*; D010080:Oxazoles / Q000737:chemistry
D000577:Amides; D010080:Oxazoles; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase