Synthetic studies on anti-infective natural products with unique structures for developing new categories of medicinal drugs

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H03810
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bioorganic chemistry
• Research Institution: Tohoku University
• Principal Investigator: Kuwahara Shigefumi 東北大学, 農学研究科, 教授 (30170145)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: amycolamicin / actinoallolide A / nonthmicin / 抗菌薬 / 抗原虫薬 / 全合成

Outline of Final Research Achievements

Total synthetic studies on amycolamicin and nonthmicin, natural products with potent and broad-spectrum antibacterial activity against various drug-resistant bacteria, as well as actinoallolide A, a natural product with potent anti-trypanosomal activity, were conducted for the purpose of developing new categories of anti-infective drugs. The A, C, D, and E units of amycolamicin have been synthesized and the assembly of the C, D, and E units has been successfully achieved. The final stage of the total synthesis is now under progress. The 12-membered macrolactone part and the side chain moiety of actionallolide A have also been synthesized and the completion of the total synthesis by Suzuki-Miyaura coupling of the two parts is now underway.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

amycolamicinのDユニット合成において，新規なビニルリチウム試薬を開発し，ケトンへの高立体選択的付加を実現した。また，デカリン構造を有するCユニットの分子Diels-Alder反応では，保護基の有無がジアステレオ選択性及び収率に大きく影響すること，actinoallolide AのTHF環内包型12員環マコロリド構造の構築にアシルケテン法が有効であることを見出した。各種類縁体の合成に応用可能な全合成の完成まであとわずかであり，構造活性相関を通した新規医薬の開発に貢献できると考える。