Collective total synthesis of unidentified natural products and structure-activity relationship on prevention of neurodegenerative disorder

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07779
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bioorganic chemistry
• Research Institution: Osaka Institute of Technology
• Principal Investigator: Kobayashi Shoji 大阪工業大学, 工学部, 准教授 (30374903)
• Co-Investigator(Kenkyū-buntansha): 長井 薫 千里金蘭大学, 生活科学部, 教授 (20340953)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 天然物 / 全合成 / 構造活性相関 / ゲラニル-レゾルシノール / アセトゲニン / 構造決定 / 小胞体ストレス / 神経細胞保護効果

Outline of Final Research Achievements

Artificial total syntheses of precious bioactive molecules that are included in medicinal mushrooms effective for prevention and treatment of dementia, and red algae unused as a resource, as well as their bioactivities against neuronal cells were studied. A divergent synthetic method to afford a variety of mushroom-derived natural products with different structures were developed. Some of the synthetic compounds exhibited neuroprotection against endoplasmic reticulum stress-dependent cell death, which is considered to be one of the causes for dementia. Furthermore, a structure-activity relationship for neuroprotection was elucidated for the first time. In addition, regarding the red algae-derived natural products, a highly-stereocontrolled synthetic method to establish all stereochemistries in the molecules were developed, and the unknown structures of natural products were identified.

Free Research Field

天然物合成化学

Academic Significance and Societal Importance of the Research Achievements

認知症をはじめとする神経変性疾患の予防や治療に役立つ可能性のある分子を合成化学的に供給する有効な手段を提供したことが最も重要な意義である。また本研究の成果は，キノコや海藻の生理機能を成分分子の働きとして理解し，活性発現の鍵となる分子の構造，分子構造と作用の相関関係，生理作用発現のメカニズムなどを解明することにも役立つ。