半日花烷型二萜天然產物 pallambins A-D 是從中國苔植物Pallavicinia ambigua 中分獲取的，這二萜中的許多化合物都呈現出有趣的生物活性。從分子結構觀點看，pallambins C 和D 由獨特的梯型[6-5-5-5]四環骨架構成，該分子骨架中包含7 個毗的體中心及三烯部分。並且，二環[3.2.1]辛烷酮片段的橋接部分分別由個橋頭甲基以及橋中的乙烯基密集取代。該分子的骨架新穎性及潛在的生物活性激發我們去進相關的全合成探。在此，我們將報導pallambins C 和D 的首次全合成。 / 本文第一章首先概述pallavicinin 系的天然源，結構特點以及生物學效用。此外，重點介紹pallambins C 和D 的分，結構鑒定以及反合成分析。 / 第二章討消旋體pallambins C 和D 的全合成細節。該合成以消旋Wieland-Miescher ketone (WMK)為起始原，經38 步線性步驟得到最終產物。該合成線突出以下個重要的化學轉化：a) 一個由Grob 碎及分子內aldol成環反應組成的多米式程，構建目標分子內關鍵的二環[3.2.1]辛烷酮單元；b) 一個由脲/鈀體系催化的烷氧羰基化增環反應，構建稠環型四氫呋喃/γ 內酯雙環框架。 / 第三章總結本文的相關研究工作。 / 第四章給出相關工作的詳細實驗據。 / Naturally occurring pallambins A-D isolated from the Chinese liverwort Pallavicinia ambigua are classified as modified labdane-type diterpenoids, many of which exhibit interesting biological activities. From a structural perspective, pallambins C and D are consisting of trienes and an unprecedented ladder-shaped [6-5-5-5] tetracyclic skeleton bearing seven contiguous stereogenic centers. Furthermore, the bridge of the bicyclo[3.2.1]octane segment is densely substituted with two methyl groups on the bridge-heads and a vinyl group on the carbon bridge. The skeletal novelty and potential bioactivities of pallambins C and D inspired us to explore their total synthesis. In this thesis, the first total synthesis of (±)-pallambins C and D is described. / In Chapter 1, a general introduction to the natural occurrence, structural features and biological potency of pallavicinin family is presented briefly. In addition, the background of pallambins C and D including isolation, structural elucidation and retrosynthetic analysis is emphasized. / In Chapter 2, detailed synthesis of (±)-pallambins C and D involving a linear 38 steps starting from the known (±)-Wieland-Miescher ketone is discussed. The synthetic approach features the following two key conversions: a) a domino process including Grob fragmentation and intramolecular aldol cyclization to build up the bicyclo[3.2.1]octanone embedded in the target molecules; b) a thiourea/palladium-catalyzed alkoxycarbonylative annulation to assemble the fused tetrahydrofuran/γ-lactone bicyclic framework. / Chaper 3 provides a conclusion of this research work. / Chapter 4 is concerned with the experimental details. / [With images.] / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Xu, Xuesong. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references. / Abstracts also in Chinese. / ACKNOWLEDGEMENTS --- p.I / CONTENTS --- p.II / ABBREVIATIONS --- p.V / PART I: / ABSTRACT --- p.1 / Chapter CHAPTER 1. --- INTRODUCTION / Chapter 1.1 --- General background --- p.4 / Chapter 1.1.1 --- General introduction to liverworts --- p.4 / Chapter 1.1.2 --- General introduction to terpenoids in liverworts --- p.5 / Chapter 1.2 --- Introduction to pallavicinin family --- p.9 / Chapter 1.2.1 --- Isolation and structural elucidation of pallavicinin compounds --- p.9 / Chapter 1.2.2 --- Synthetic advances on pallavicinin family --- p.13 / Chapter 1.3 --- Introduction to the present research --- p.16 / Chapter 1.3.1 --- Structural elucidation and features of pallambins C and D --- p.16 / Chapter 1.3.2 --- Biogenetic hypothesis and retrosynthetic analysis of pallambins C and D --- p..20 / Chapter 1.4 --- Aim of the present work --- p.22 / Chapter CHAPTER 2. --- RESULTS AND DISCUSSION --- p.24 / Chapter 2.1 --- Previous synthetic effort on pallambin D (2) --- p.24 / Chapter 2.2 --- Successful synthetic approach to 1 and 2 --- p.25 / Chapter 2.2.1 --- Synthesis of compound 24 --- p.25 / Chapter 2.2.2 --- Synthesis of compound 14 --- p.30 / Chapter 2.2.3 --- Synthesis of compound 13 --- p.37 / Chapter 2.2.4 --- Synthesis of compound 12 --- p.43 / Chapter 2.2.5 --- Synthesis of 1 and 2 --- p.53 / Chapter CHAPTER 3. --- CONCLUSION --- p.60 / Chapter CHAPTER 4. --- EXPERIMENTAL SECTION --- p.62 / REFERENCES --- p.104 / PART II: / ABSTRACT --- p.110 / Chapter CHAPTER 1. --- INTRODUCTION --- p.113 / Chapter 1.1 --- Introduction to bicyclo[3.2.1]octane skeleton --- p.113 / Chapter 1.1.1 --- Structural features of bicyclo[3.2.1]octane --- p.113 / Chapter 1.1.2 --- Bicyclo[3.2.1]octane-containing bioactive natural products --- p.114 / Chapter 1.1.3 --- Methodologies for synthesis of bicyclo[3.2.1]octane derivatives --- p.116 / Chapter 1.1.4 --- Gold-catalyzed construction of bicyclo[3.2.1]octane unit --- p.117 / Chapter 1.2 --- Background of the present research --- p.119 / Chapter 1.2.1 --- Introduction to dhilirolides A-D --- p.119 / Chapter 1.2.2 --- Retrosynthetic analysis of dhilirolide A (1) --- p.121 / Chapter 1.3 --- Aim of the present work --- p.122 / Chapter CHAPTER 2. --- RESULTS AND DISCUSSION --- p.124 / Chapter 2.1 --- Synthesis of the key acetal allene precursor 6 --- p.124 / Chapter 2.1.1 --- Preparation of the starting dimethoxyl ketone 7 --- p.124 / Chapter 2.1.2 --- Preparation of alkynyl furan 11 --- p.126 / Chapter 2.1.3 --- Preparation of acetal allene 6 --- p.128 / Chapter 2.2 --- Synthesis of bicyclo[3.2.1]octenone derivative 5 --- p.134 / Chapter 2.3 --- Synthesis of mono-tosylate 26 --- p.138 / Chapter CHAPTER 3. --- CONCLUSION --- p.141 / Chapter CHAPTER 4. --- EXPERIMENTAL SECTION --- p.143 / REFERENCES --- p.162 / APPENDIX --- p.167
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_328666 |
| Date | January 2013 |
| Contributors | Xu, Xuesong., Chinese University of Hong Kong Graduate School. Division of Chemistry. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, bibliography |
| Format | electronic resource, electronic resource, remote, 1 online resource (viii, 284 leaves) : ill. (some col.) |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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