Bottom-up synthesis of hyaluronan and its derivatives via enzymatic polymerization: direct incorporation of an amido functional group.
Bottom-up synthesis of hyaluronan and its derivatives via enzymatic polymerization: direct incorporation of an amido functional group.
复制标题
通过酶聚合自下而上合成透明质酸及其衍生物：直接掺入酰胺基官能团。
作者：
Hirofumi Ochiai;M. Ohmae;Tomonori Mori;Shiro Kobayashi
本文报道了透明质酸酶催化2-取代恶唑啉衍生物单体聚合合成透明质酸（HA）及其衍生物。由N-乙酰基透明质酸酯（GlcAbeta（1->3）GlcNAc）聚合的2-甲基恶唑啉单体在pH 7.5和30 ℃下有效地进行，在区域选择性和立体化学的完全控制下通过开环聚合加成以78%的最佳产率产生合成HA（天然型）。透明质酸酶催化使得2-乙基、2-正丙基和2-乙烯基单体能够聚合，以良好的产率提供在所有葡糖胺单元的C2位分别具有N-丙酰基、N-丁酰基和N-丙烯酰基官能团的相应HA衍生物（非天然型）。2-异丙基恶唑啉衍生物以低产率提供HA的N-异丁酰基衍生物。2-苯基和2-异丙烯基恶唑啉衍生物的单体不聚合。讨论了聚合反应机理。
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.