Development of stereoselective glycosylation using alkoxymethyl groups and application to the total synthesis of natural products

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K05462
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38040:Bioorganic chemistry-related
• Research Institution: Kyushu University
• Principal Investigator: Torikai Kohei 九州大学, 理学研究院, 助教 (20456990)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: グリコシル化 / 1,2-トランス / 糖鎖 / 隣接基関与 / アルコキシメチル基 / β選択的 / NAPOM基 / ワンポット

Outline of Final Research Achievements

Before starting this project, only one example for the glycosylation of 2-O-alkoxymethyl (AM) donor, in which 1,2-cis selectivity had been observed for a 2-O-methoxymethyl donor, was reported. Contrary to it, we envisaged that reversed selectivity should appear if the oxygen atom of AM participates the oxocarbenium ion. After our considerable experimentation (with more than dozens of examples), we found that all the reactions gave 1,2-trans glycosides. Furthermore, we found that AM donors had higher reactivity than traditional 2-O-acyl donors and thus developed a one-pot iterative glycosylation strategy. In addition, during the development of the above one-pot strategy, we created a simple apparatus to add solid materials under inert atmosphere without any contamination by air.

Free Research Field

有機合成化学，天然物有機化学

Academic Significance and Societal Importance of the Research Achievements

本研究では，1例の誤った情報から1,2-cis選択的であると考えられていた2-O-アルコキシメチル（AM）糖供与体のグリコシル化が，本当は1,2-trans選択的に進行することを世界で初めて報告した．さらに2-O-AM供与体が，非常に高い反応性を有することを見出した．これらは糖鎖合成化学に大きなインパクトをもたらした．

さらに不活性ガス雰囲気下の固体試料添加に一つの答えを提供したことは，糖鎖合成化学者のみならず有機・無機を問わず合成化学に携わる全ての研究者の助けとなると考えられる．さらに物理化学等への応用も期待できる．これを機に化学がより加速度的に発展すれば学術はもちろん社会的意義にもつながる．