2019 Fiscal Year Final Research Report
Total Synthesis, Structure Determination, and Bioactive Stereostructure of Complex Macrolides
| Project/Area Number |
17K01941
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biomolecular chemistry
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| Research Institution | Chuo University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 全合成 / 構造決定 / 立体配置 / NMR解析 / タンデム反応 / 閉環メタセシス |
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| Outline of Final Research Achievements |
Total synthesis of the proposed structure of iriomoteolide-2a has been achieved. Our synthesis involved: 1) convergent assembly of important fragments via a Suzuki-Miyaura reaction and an esterification, and 2) forging the macrocyclic skeleton by means of a ring-closing metathesis. However, the NMR spectra of our synthetic material did not match those of natural iriomoteolide-2a. Synthesis/NMR analysis of model compounds and careful inspection of the NMR data of the authentic sample, followed by total syntheses of possible structures enabled us to determine the absolute configuration of iriomoteolide-2a.
Total synthesis of enigmazole A has been completed. The salient features of our synthesis include: 1) a stereoselective tandem synthesis of the tetrahydropyran ring, 2) a Au(I)-catalyzed Meyer-Schuster rearrangement of a propargylic benzoate, and 3) a macrocyclic ring-closing metathesis.
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| Free Research Field |
天然物化学
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| Academic Significance and Societal Importance of the Research Achievements |
海洋生物が生産する二次代謝産物（天然物）は、生物活性物質の構造多様性の源泉であり、新たな新薬の候補化合物の宝庫である。しかし、海洋天然物の多くは自然界には微量しか存在しないため、化学合成による化合物供給が天然物創薬には必須である。本研究では抗腫瘍性海洋天然物iriomoteolide-2aおよびenigmazole Aの完全化学合成（全合成）を達成した。これにより天然物および構造改変体の人工供給が可能となり、構造活性相関や活性発現機構の解析へと研究を展開するための基盤を確立した。
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