Study toward Rational Simplification of on Polyketides and Creation of Bioactive Molecules

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03366
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
• Research Institution: Toyama Prefectural University
• Principal Investigator: Urabe Daisuke 富山県立大学, 工学部, 教授 (80503515)
• Co-Investigator(Kenkyū-buntansha): 深谷 圭介 富山県立大学, 工学部, 助教 (40821575) ; 生城 真一 富山県立大学, 工学部, 教授 (50244679)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 有機合成化学 / 天然物化学 / NMR計算 / 分子設計

Outline of Final Research Achievements

Polyketides are attractive leads for drug development because of their diverse structures and biological activities. On the other hand, structural modification, especially simplification, of bioactive natural products, toward drug discovery, is difficult, and no rational standard process has been established. In this study, three rare polyketides were selected as targets for developing rational process for simplification of structures focusing on their unique conformations. When the study was started , the structures of the three polyketides had not been fully elucidated. Therefore, the structures of formosalide A and amphidinolide L were estimated by NMR calculations. Synthetic studies of the deduced structures led to establishment of the efficient synthetic route to the C1-C18 fragment of formosalide A and the C20-C26 fragment of amphidinolide L.

Free Research Field

化学系薬学

Academic Significance and Societal Importance of the Research Achievements

NMR計算によってホルモサリドAとアンフィジノリドLの構造を推定した際に、置換基の立体化学によって配座(3次元的な立体構造)が大きく異なるという知見を得た。この知見を基盤にすれば、ホルモサリドAとアンフィジノリドLの多様な立体異性体の供給を見据えて確立した合成法は、多様な3次元をもつ模倣分子や簡略化分子が設計・供給を可能にすることを意味する。天然物創薬を加速する合理的プロセスとして、生物活性物質の3次元構造の再現と構造簡略化の重要性の追求を、本研究で具現化しつつある。