Development of strategy toward the unified total synthesis of natural and artificial daphnan/tigrian diterpenoids and discovery of new functional molecules

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K15554
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 33020:Synthetic organic chemistry-related
• Research Institution: The University of Tokyo
• Principal Investigator: Nagatomo Masanori 東京大学, 大学院薬学系研究科(薬学部), 講師 (70634161)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 全合成 / 天然有機化合物 / 中分子 / テルペノイド / ラジカル反応 / 高酸化度天然物 / 統一的合成戦略 / リード化合物

Outline of Final Research Achievements

Rhamnofolane, tigliane, and daphnane diterpenoids are known to exhibit a wide range of important biological activities depending on their substituent patterns and have great potential for the discovery of new drugs. However, it is extremely difficult to utilize these highly oxidized middle-molecular diterpenes as lead compounds for new drugs due to the complexity of their chemical structures. In this study, we attempted to solve this problem, which is of high social importance. As a result, we established a method for the construction of the tricyclic synthetic intermediate with the common carbon skeleton. We achieved the total synthesis of three natural products, resiniferatoxin, prostratin, and crotophorbolone from the common intermediates, all in about 20 steps from the starting materials.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

本成果は、生物資源からの単離利用が限定的であったこれら天然物群の量的供給を可能にするものであり、多様な類縁体合成を基盤とした創薬研究の発展に寄与することが期待される。すなわち、ここで確立された独創的な合成戦略と保護基戦略は、天然および人工のラムノフォラン、チグリン、ダフナンジテルペノイドの多様な全合成を加速させ、それらの様々な生物学的機能の詳細な調査と治療活性の向上につながる。