Synthetic chemistry for the development of oligosaccharide-type sialidase inhibitors

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H02097
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
• Research Institution: Kyushu University
• Principal Investigator: Hirai Go 九州大学, 薬学研究院, 教授 (50359551)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: シアル酸 / シアリダーゼ / 阻害剤 / C-H挿入反応 / グリコシル化

Outline of Final Research Achievements

We have found that novel disaccharide analogues are effective inhibitors of sialidase despite their substrate structure. Conversion to oligosaccharide structure from these analogs is expected to be a more effective inhibitors for sialidases. Therefore, in this study, we worked to establish an efficient synthetic method. Although we could not achieve the site-selective C-H insertion reaction at the C3 position, we succeeded in introducing acetic acid or malonic acid units by oxidative radical coupling, and achieved the modification of C3-position of the sialic acid in only four steps. Furthermore, the results suggest that this route may also improve the efficiency of glycosylation, which was another problem.

Free Research Field

生物有機化学・有機合成化学

Academic Significance and Societal Importance of the Research Achievements

本研究では、インフルエンザなどの感染症や、がんなどに関与する酵素であるシアリダーゼの新たな阻害剤を開発するための、基盤となる有機合成研究である。これまでの工程数を半減するルートの開拓を目指し、種々検討した結果、これまでの問題点をほぼ克服した新たな合成経路を見出すことに成功した。今回得た成果をさらに発展させることで、この新たなシアリダーゼ阻害剤をより効率的に合成でき、さらに効果的な阻害剤創製につながることが期待される。