Synthesis and function search of all-nitrogen sugars

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22189
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 33:Organic chemistry and related fields
• Research Institution: Keio University
• Principal Investigator: Chida Noritaka 慶應義塾大学, 理工学部(矢上), 教授 (50197612)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: 全窒素糖 / 連続的Overman転位 / 多重シグマトロピー転位

Outline of Final Research Achievements

All-nitogenated sugars, in which all hydroxy groups in a normal sugar are replaced with amino groups, are expected to possess useful biological activities, but no report on the synthesis of all-nitogenated sugar has appeared. In this study, short-step synthesis of all-nitorogenated sugars having 5- and 6-carbons starting from aldohexoses utilizing sequential Overman rearrangements, are carried out, and the following positive results were obtained. 1) D-Galactose was converted to pentakisimidate, which underwent sequential Overman rearrangements upon heating, to afford the five-time rearranged products. The rearranged compound was transformed to D-glucofuranose-type all-nitrogenated sugar. By this procedure, nine all-nitorgenated sugars have been synthesized. 2) Biological assessment of all-nitogenated sugars and their derivatives revealed that the L-arabinofuranose-type possessing cholesterol as an aglycon exhibited antiproliferative effects against human cancer cell lines.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

本研究において、全窒素糖を世界に先駆けて合成することに成功した。入手容易な単糖（グルコース、アラビノースなど）から合成したアリルポリオールに連続的多重Overman転位を施すことにより、効果的に糖の水酸基をアミノ基に変換し、短工程で全窒素糖を合成する経路を確立した。合成した全窒素糖の誘導体がヒトがん細胞に対し細胞毒性を示すことを見出し、新規有用物質の創成に資することができた。