Isolation and synthetic study of plant alkaloids possessing antitumor activity

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03395
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 47050:Environmental and natural pharmaceutical resources-related
• Research Institution: Chiba University
• Principal Investigator: KITAJIMA Mariko 千葉大学, 大学院薬学研究院, 准教授 (60195261)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 天然活性物質 / 生物活性物質の探索 / アルカロイド / 化学合成 / 構造解析

Outline of Final Research Achievements

Alkaloids including new minor constituents were isolated from medicinal plant resources such as Apocynaceae, Gelsemiaceae, Rubiaceae, and Loganiaceae plants. Three new monoterpenoid indole alkaloids with a unique structure were found from Gelsemium elegans and asymmetric total synthesis of a gelsedine-type compound gelsevietmine-A was accomplished. A new pentacyclic monoterpenoid indole alkaloid glycoside secorubenine was isolated from Adina rubescens and its enantioselective total synthesis was accomplished. Asymmetric total synthesis of huperzine H, a Lycopodium alkaloid with a novel skeleton, was achieved and its relative and absolute stereochemistry was established. Asymmetric total synthesis of some monoterpenoid indole alkaloids were studied. Evaluation of biological activities of isolated and synthetic compounds is in progress.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

現在の超高齢社会においてがんの罹患数と死亡数はともに増加し続けており、がんに対応するための新しい治療薬の開発が強く望まれている。本研究では、薬用資源植物からの抗腫瘍活性を有するアルカロイドの探索と、生物活性評価用サンプルの供給と合成法の確立に向けた微量天然アルカロイドなどの不斉全合成研究を実施し、新規微量アルカロイド類の取得とアルカロイド類の不斉全合成を達成した。今後、これら化合物の生物活性評価や構造活性相関研究等を進めることで新規抗腫瘍薬開発のためのシード分子の取得へとつながることが期待できる。