Efficient synthetic study of tutin and its novel derivatives

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K15549
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 33020:Synthetic organic chemistry-related
• Research Institution: Hokkaido University
• Principal Investigator: Ikeuchi Kazutada 北海道大学, 理学研究院, 助教 (70756676)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: ツチン / コリアミルチン / 全合成 / 分子内アルドール反応

Outline of Final Research Achievements

Tutin is one of picrotoxane sesquiterpenoids isolated from Coriaria species. The structure feature is a highly congested functionalization in 5,6-cis fused skeleton. Although tutin shows neurotoxin, recent work reported that its derivatives do not show the bioactivity. To establish the synthetic method of the complex structure and elucidate the difference of bioactivities, their total synthesis was examined. As the result of several investigations, I achieved the formal synthesis of coriamyrtin where a hydroxy group at the C-2 position in tutin lacks. The key steps for constructing the 5,6-cis fused skeleton used L-proline mediated intramolecular aldol reaction. To apply the reaction for the synthesis of tutin, the development of the efficient synthetic method of its precursor is now being conducted.

Free Research Field

有機合成

Academic Significance and Societal Importance of the Research Achievements

確立したコリアミルチンの合成経路は他の天然物合成へのアクセスが容易である。例えば、分子内アルドール反応によって得られる5,6-cis縮環化合物は５員環上にケトンを有するため、それを足がかりにピクロトキシニンやコリアノールなどのツチン類縁体合成への発展が見込める。また、脱水を経由して橋頭位のヒドロキシ基を水素に置換すれば、他の種類のデンドルビンセスキテルペンの合成研究も可能となる。