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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳榮傑 | zh_TW |
| dc.contributor.advisor | Rong-Jie Chein | en |
| dc.contributor.author | 黃柔潔 | zh_TW |
| dc.contributor.author | Rou-Jie Huang | en |
| dc.date.accessioned | 2025-08-21T17:00:24Z | - |
| dc.date.available | 2025-09-02 | - |
| dc.date.copyright | 2025-08-21 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2025-08-05 | - |
| dc.identifier.citation | [1] Huang, R.-J.; Ong, T.-G.; Chein, R.-J. Total synthesis of cassane-type diterpenoid pikrosalvin. J. Chin. Chem. Soc. 2023, 70, 2127−2135.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/99255 | - |
| dc.description.abstract | 本論文第一章敘述 (±)-pikrosalvin、(+)-simplexene C、(+)-simplexene D 和 (±)-swartziarboreol G 之全合成。合成關鍵步驟為仿生多烯環化與內酯化反應，此仿生合成途逕來自於Stork–Eschenmoser 的假說啟發，可以有效地構建這些天然物特有的A/B環結構、芳香族C環以及內酯D環。以香草酸與香葉醇為起始物，經官能基轉換與保護後引入三甲基矽基團，並利用一鍋化反應生成二烯中間體。此中間體經碘化鋅或三氟甲磺酸鋅搭配對甲苯磺酸催化多烯環化，建構反式十氫萘骨架。三甲基矽基團轉換為碘化物後，經偶聯反應生成苯乙烯衍生物，再進行內酯化反應形成甲基內酯，並在水解甲基芳基醚後完成 (±)-pikrosalvin 之合成，此部分研究成果已發表。
以同樣苯乙烯衍生物經氧化內酯化、去保護及層析分離獲得四個異構物，其中一個為 (+)-simplexene C，另一異構物經水解甲基芳基醚後得到 (+)-simplexene D。此外，將苯乙烯衍生物中的醯胺轉為羧酸，經乙酰氧基內酯化建構六環後，獲得四個同分異構物，經結晶與 X 光單晶繞射確認結構，最終去保護得到 (±)-swartziarboreol G。此全合成共歷經十一至十四步。 第二章探討麥角生物鹼 (−)-chanoclavine-I 之合成研究。因其六環的生合成機制至今仍未明確，我們提出一種仿生合成策略，嘗試以氨基酸合成 (−)-chanoclavine-I。關鍵步驟包括環氧化的合成及光催化去羧基環化反應，本研究仍在進行中。 第三章探討一種結合 (−)-conidiogenone 與 meleagrin 的特殊萜烯–生物鹼混合型天然物 meleagrin B 之生物合成途徑。林曉青老師發現 (−)-conidiogenone B 可經雙萜合酶與 P450 單加氧酶催化生成，隨後與咪唑在 α,β-水解酶（Con-ABH）催化下進行 aza-Michael 加成反應，形成 3S-imidazolyl conidiogenone B。我們以化學合成方式獲得該化合物，並藉X光單晶繞射確認其絕對立體結構，提供給林老師做更進一步研究，此研究成果已發表。 第四章探討一種蕈類次級代謝物 (−)-antrocin，其被推測由法尼基焦磷酸 (FPP) 經萜烯環化酶催化生成，但其生合成機制尚未完全明瞭。在林曉青老師的研究中，發現 (+)-albicanol 為FPP轉化為 (−)-antrocin的中間體。為探討此轉化過程中萜烯環化酶的作用，我們以化學合成方法 (+)-albicanyl pyrophosphate，利用(+)-sclareolide 為起始物，經六步反應成功獲得 (+)-albicanyl pyrophosphate，並將其提供給林老師作為生合成中間體做測試，證實酵素 AncC 在此合成機制中具有兩個功能區域：萜類環化酶 (terpene cyclase, TC) 與焦磷酸酶(pyrophosphatase, PPase)。其中，TC 區域可將 FPP 環化生成 (+)-albicanyl pyrophosphate，接著由 PPase 區域催化去除焦磷酸基團，產生 (+)-albicanol。此研究成果已發表。 | zh_TW |
| dc.description.abstract | The total synthesis of four cassane-type diterpenoids, pikrosalvin, simplexene C, simplexene D, and (±)-swartziarboreol G, was accomplished via a biomimetic polyene cyclization strategy followed by a late-stage lactonization, completed in 11–14 steps from commercially available vanillic acid and geraniol. This synthetic approach, inspired by the Stork–Eschenmoser hypothesis, enabled the efficient construction of the decalin A/B rings, the aromatic C ring, and the lactone D ring characteristic of these natural products. This part of the study has been published.
Chapter two explores the synthetic studies of the ergot alkaloid (−)-chanoclavine-I. Since the biosynthetic mechanism of its 6-membered ring remains unclear, we propose a biomimetic synthetic strategy that attempts to access (−)-chanoclavine-I from amino acid precursors. Key steps include the construction of the epoxide intermediate and a photoredox-catalyzed decarboxylative cyclization. This research is still ongoing. In chapter three, the biosynthesis of Meleagrin B, a unique terpene–alkaloid hybrid natural product combining (−)-conidiogenone and meleagrin scaffolds, was investigated. We characterized the enzyme-mediated pathway in which a diterpene synthase and a P450 monooxygenase generate (−)-conidiogenone B, followed by an α,β-hydrolase (Con-ABH)-catalyzed aza-Michael addition with imidazole to form 3S-imidazolyl conidiogenone B. This hybrid compound was chemically synthesized, and its absolute configuration was confirmed by X-ray crystallography. This work has been published. Chapter four investigates the biosynthesis of a fungal secondary metabolite, (−)-antrocin. Its biosynthetic mechanism has not yet been fully elucidated. In this study, we identified (+)-albicanol as an intermediate in the conversion of FPP to (−)-antrocin. To investigate the role of the terpene cyclase involved in this transformation, we chemically synthesized (+)-albicanyl pyrophosphate from (+)-sclareolide in six steps. This compound was then tested as a biosynthetic intermediate, confirming that the enzyme AncC possesses two functional domains in the biosynthetic mechanism: a terpene cyclase (TC) and a pyrophosphatase (PPase). The TC domain first cyclizes FPP to form (+)-albicanyl pyrophosphate, which is subsequently dephosphorylated by the PPase domain to yield (+)-albicanol. This work has been published. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-08-21T17:00:24Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-08-21T17:00:24Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 誌謝 ii
中文摘要 iii Abstract v Table of Contents viii List of Schemes xiii List of Figures xvii List of Tables xviii Abbreviations xix Chapter 1. Total Synthesis of (±)-Pikrosalvin,1 (+)-Simplexene C, (+)-Simplexene D and (±)-Swartziarboreol G 1 1.1 Introduction 1 1.1.1 Background 1 1.1.2 Review of the Total Synthesis of Cassane-Type Natural Products 4 1.1.3 Polyene Cyclization 6 1.2 Result and Discussion 9 1.2.1 Retrosynthetic Analysis 9 1.2.2 Synthesis of Compound (±)-27 through Biomimetic Polyene Cyclization 10 1.2.3 Total Synthesis of (±)-Pikrosalvin (1),1 (+)-Simplexene C (10) and (+)-Simplexene D (11) 13 1.2.4 Hydrolysis of Amide (±)-26 under Basic Conditions 15 1.2.5 Lactonization of Amide (±)-26 under Acidic Conditions 17 1.2.6 Convert Amide (±)-26 to Acid (±)-37 through Methyl Ester 18 1.2.7 Total Synthesis of (±)-Swartziarboreol G (8) 20 1.2.8 Enantioselective Polyene Cyclization 23 1.3 Conclusion 26 Chapter 2. Synthetic Studies toward Ergot Alkaloid (–)-Chanoclavine I 27 2.1 Introduction 27 2.1.1 Background of Ergot Alkaloid (–)-Chanoclavine I 27 2.1.2 Possible Mechanism from L-Tryptophan to (–)-Chanoclavine I (61) 29 2.1.3 Literature Review of the Total Synthesis of (−)-Chanoclavine I (61) 31 2.1.4 Photoredox Catalysis Enabling Decarboxylative Radical Cyclization 33 2.2 Results and Discussion 36 2.2.1 Retrosynthetic Analysis I 36 2.2.2 Synthesis of β-Iodo-L-alanine 81, N-Cbz Diene 86, N-Cbz Epoxide 92 37 2.2.3 Retrosynthetic Analysis II 44 2.2.4 Synthesis of Epoxide via Regioselective C3-Alkylation and Examination of Photoreaction 45 2.2.5 Replace Methyl Ester to Butyl Ester to Synthesize Epoxide for Photoreaction. 53 2.2.6 Synthesis of Free-Protected Epoxide 57 2.2.7 Introduction of a Photocleavable Protecting Group for Application in Decarboxylative Cyclization Reaction 58 2.2.8 Cyclization Enabled by Leaving Group Installation on the Side Chain 71 2.3 Conclusions 74 Chapter 3. Biosynthetic Investigation of the Terpene–Alkaloid Hybrid Meleagrin B2 75 3.1 Introduction 75 3.1.1 Background 75 3.1.2 Hybridization of (−)-Conidiogenone B (160) and Meleagrin (162) via Aza-Michael Addition 78 3.1.3 Synthesis of Imidazole–(−)-Conidiogenone B via Aza-Michael Addition 79 3.2 Results and Discussion 80 3.2.1 A Model Substrate for Aza-Michael Addition 80 3.2.2 Aza-Michael Addition of (−)-Conidiogenone B (160) and Imidazole 81 3.2.3 Aza-Michael Addition of (−)-Conidiogenone B (160) and Meleagrin (162) 84 3.3 Conclusions 87 Chapter 4. Biosynthetic Investigation of the Mushroom-Derived Natural Product (−)-Antrocin 3 88 4.1 Introduction 88 4.1.1 Background 88 3.1.2 Biosynthetic Pathway of (−)-Antrocin (166) from Farnesyl Pyrophosphate (FPP) 88 4.2 Results and Disscusion 91 4.3 Conclusions 94 References 95 Supporting Information 105 1. General Methods 105 2. Pictures of Photoredox-Catalyzed Reaction Experimental Setup 106 3. Experimental Procedures 107 4. NMR Spectral Data 169 5. X-ray Crystallographic Data 302 6. HPLC data 349 | - |
| dc.language.iso | en | - |
| dc.subject | 雙萜化合物 | zh_TW |
| dc.subject | 天然物全合成 | zh_TW |
| dc.subject | 蕈類天然物 | zh_TW |
| dc.subject | 仿生策略 | zh_TW |
| dc.subject | 生物合成機制 | zh_TW |
| dc.subject | 多烯環化反應 | zh_TW |
| dc.subject | 麥角生物鹼 | zh_TW |
| dc.subject | total synthesis | en |
| dc.subject | cassane-type diterpenoid | en |
| dc.subject | hybrid compound | en |
| dc.subject | natural product synthesis | en |
| dc.subject | biomimetic strategy | en |
| dc.subject | mushroom-derived natural product | en |
| dc.subject | biosynthetic investigation | en |
| dc.subject | polyene cyclization | en |
| dc.title | Cassane 類雙萜化合物與麥角生物鹼 (−)-Chanoclavine-I 之全合成；雜環萜類天然物 Meleagrin B 與蕈類天然物(−)-Antrocin 的生物合成途徑研究 | zh_TW |
| dc.title | Total Synthesis of Cassane-Type Diterpenoids and the Ergot Alkaloid (−)-Chanoclavine-I; Biosynthetic Investigation of the Terpene–Alkaloid Hybrid Meleagrin B and the Mushroom-Derived Natural Product (−)-Antrocin | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-2 | - |
| dc.description.degree | 博士 | - |
| dc.contributor.coadvisor | 王朝諺 | zh_TW |
| dc.contributor.coadvisor | Tiow-Gan Ong | en |
| dc.contributor.oralexamcommittee | 李瑜章;林曉青;侯敦仁;謝俊結 | zh_TW |
| dc.contributor.oralexamcommittee | Yu-Jang Li;Hsiao-Ching Lin;Duen-Ren Hou;Jiun-Jie Shie | en |
| dc.subject.keyword | 天然物全合成,雙萜化合物,麥角生物鹼,多烯環化反應,生物合成機制,仿生策略,蕈類天然物, | zh_TW |
| dc.subject.keyword | total synthesis,biomimetic strategy,natural product synthesis,polyene cyclization,biosynthetic investigation,mushroom-derived natural product,hybrid compound,cassane-type diterpenoid, | en |
| dc.relation.page | 349 | - |
| dc.identifier.doi | 10.6342/NTU202503325 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2025-08-08 | - |
| dc.contributor.author-college | 理學院 | - |
| dc.contributor.author-dept | 化學系 | - |
| dc.date.embargo-lift | N/A | - |
| 顯示於系所單位： | 化學系 | |
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