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2023 Fiscal Year Final Research Report

Synthesis and evaluation of novel tricyclic alkaloid derivatives using sequential Henry reaction toward anti-cancer drugs

Research Project

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Project/Area Number 19K05486
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 33020:Synthetic organic chemistry-related
Research InstitutionKagawa Nutrition University

Principal Investigator

AKAI SHOJI  女子栄養大学, 栄養学部, 教授 (00322537)

Project Period (FY) 2019-04-01 – 2024-03-31
Keywordsパンクラチスタチン / ニトロアルドール / Henry反応 / アナログ / 抗腫瘍活性
Outline of Final Research Achievements

To create novel lead compounds for anticancer drugs from one of the tricyclic natural alkaloids, pancratistatin, we conducted a synthetic study of novel derivatives by combining the sequential Henry reaction and diversity-oriented synthesis. As a result, three 2-position derivatives (deoxy, epi, and methoxy) were synthesized, and the synthesis of 2-fluorinated derivatives is also in progress. Additionally, the sequential Henry reaction discovered a novel method for synthesizing 5-6-6 membered derivatives with a reduced A-ring of the natural product. This demonstrates the effectiveness of diversity-oriented synthesis for the synthesis of derivatives. Furthermore, cytotoxicity studies of the 2-position derivatives revealed that the interaction of the 2-position OH group is crucial for the expression of activity, providing valuable insights for creating lead compounds.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

パンクラチスタチンの2位誘導体の合成とその活性試験により、2位OH基が活性発現に極めて重要であることを明らかにすることができた。また、A環のサイズを小さくした5-6-6員環誘導体の合成は比較的容易で、選択性や活性のまったく異なる新たな物質の創製につながる多くの知見が得られた。研究の基軸となる連続Henry反応を用いるパンクラチスタチンの全合成法は、様々な誘導体の合成に優れ、2位をフッ素原子に置換した誘導体は、応用研究により癌組織のイメージングへと発展可能な点で学術的意義の高い研究と言える。このような低分子医薬の基礎研究は、社会的要請の高い抗がん剤へとつながるものであり、社会的意義も十分である。

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Published: 2025-01-30  

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