Development for the New Method for Divergent Total Synthesis of Highly Oxygenated Natural Products with Steroidal Tetracycles

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K14622
• 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: Hagiwara Koichi 東京大学, 大学院薬学系研究科(薬学部), 特任助教 (20804371)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 有機化学 / 天然物合成化学 / ステロイド / カップリング反応 / ラジカル反応

Outline of Final Research Achievements

This research aimed to establish a new method for divergent total synthesis of highly oxygenated natural products with steroidal tetracycles, which show potent and diverse bioactivities. This time, I established a new strategy in which a convergent coupling of highly oxygenated AB-ring and D-ring followed by the C-ring construction by a radical or an anionic reaction was utilized to construct the steroidal tetracycles in efficient manner. By using this strategy, I synthesized the key intermediate for the synthesis of cardenolides and bufadienolides, and also achieved the efficient total synthesis of a complex steroidal alkaloid, batrachotoxin (22 steps).
In future, I will apply this strategy to the synthesis of various highly oxygenated steroidal natural products.

Free Research Field

天然物合成化学

Academic Significance and Societal Importance of the Research Achievements

本研究では、強力かつ多様な生物活性を有するステロイド様化合物が有する4環性骨格の新規効率的構築法を開発した。本手法を用いて、複雑天然物であるバトラコトキシンの全合成を達成した。本手法を応用し、使用するフラグメントの酸化度を変更することで、様々な酸化度のステロイド様天然物の全合成へと展開可能であり、ステロイド様化合物を基盤とした創薬研究の発展も期待できる。従って、有機合成化学・創薬化学の観点から重要な研究成果が得られたと言える。