Chemoenzymatic Synthesis of Neu5Ac and KDN Derivatives

• Main Authors: Chi-Hao Chang, 張志豪
• Other Authors: Shih-Hsiung Wu
• Format: Others
• Language: zh-TW
• Published: 2001
• Online Access: http://ndltd.ncl.edu.tw/handle/73726311791862448493

碩士 === 國立臺灣大學 === 生化科學研究所 === 89 === By virtue of their importance in medicine, sialic acid acetylated derivatives have been considered to be synthesized via different strategies, including conventional organic chemistry or chemoenzymatic methods. Compared with the chemoenzymatic methods, the conventional organic synthesis is more complicated and time-consuming due to many steps in protection and deprotection. Using peracetylated sialic acid derivatives as substrates, we apply different kinds of lipases from microorganisms, including lipase OF, MY, CCL, OR, AK, AY, R, MAP10 and AP6, for the preparation of sialic acid acetylated derivatives by deacetylation. In our experiments, the substrate compounds 9, 10, 16, 17 were prepared first, and then each compound was tested with lipases. Among the lipases, lipase AP6 was found to be suitable for the deacetylation of peracetylated sialic acid derivatives. Lipase AP6 showed better selective deacetylation for b form of silaic acid derivatives, while showed faster hydrolytic rate for a form of sialic acid derivatives. Compounds 11, 12, 13 and 18 were isolated and purified from the deacetylation of a and b forms. With the analyses of NMR and MS data, copmpounds 11, 12, 13 and 18 were identified as Neu4,5Ac2, Neu4,5,7Ac3, Neu5Ac and fully deacetylated KDN derivative. However, compounds 19 and 20 were obtained in trace amount and their structures could not be determined, only identified as derivatives with 2 and 1 acetyl groups, respectively.