2022 Fiscal Year Final Research Report
Development of strategy towards the unified total syntheses of premyrsinane and jatrophane diterpenoids orienting new drug discovery
Project/Area Number |
21K14745
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
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Research Institution | The University of Tokyo |
Principal Investigator |
Fujino Haruka 東京大学, 大学院薬学系研究科(薬学部), 特任助教 (60897023)
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Project Period (FY) |
2021-04-01 – 2023-03-31
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Keywords | 全合成 / テルペノイド / 中分子 / 統一的合成戦略 / ラジカル反応 |
Outline of Final Research Achievements |
Densely oxygenated premilarsinanes are a diterpenoid family that exhibits a variety of biological activities depending on the stereochemistry and oxygen functional group patterns and thus have great potential for new drug discovery. However, their intricately-fused tetracyclic structure imposes a formidable challenge on their chemical synthesis. As a result, the total synthesis of these natural products has not yet been accomplished. This time, we envisaged and attempted two distinct synthetic strategies for the first total synthesis of these natural products. In both routes, radical-based transformations are implemented as powerful tools connecting the sterically-cumbersome carbon-carbon bonds in a highly diastereoselective fashion, without affecting polar functional groups of architecturally-complex synthetic intermediates. These results illustrate the potential of radical reaction for further application in the total syntheses of other densely functionalized natural products.
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Free Research Field |
有機合成化学
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Academic Significance and Societal Importance of the Research Achievements |
本研究成果は、現代の有機合成化学の発展をもってしてもなお達成困難な高酸化度複雑テルペノイドの、ラジカル戦略を基盤とする新しい全合成論を提供するものである。高酸化度複雑テルペノイドの多くは強力かつ多彩な生物活性を示す優れた創薬特性を有するにもかかわらず、天然からの単離量が僅少であるという量的制限のため、従来創薬題材分子として未活用であった。したがって、本研究で確立した合成戦略は、プレミルシナン類のみならず多様な構造クラスの高酸化度複雑テルペノイドの合成研究を加速かつ効率化しうる。そのため本研究は、創薬科学を端緒とする普遍的な科学技術・公衆衛生分野に大きな波及効果を与えうる重要な基礎研究である。
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