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

The pyrrolo[3,2,1-ij]quinolin-6-one ring system was synthesised from 3-aryl-4,6-dimethoxyindoles and 2,3-disubstituted-4,6-dimethoxyindoles. The reaction of 4,6-dimethoxyindoles under Friedel-Crafts or Vilsmeier-Haack acylation gave the 2- and 7-indolyldeoxybenzoins in good yield. Cyclisation of 7-indolyldeoxybenzoins with N,N-dimethylformamide dimethyl acetal as a one carbon reagent gave the pyrroloquinolin-6-ones in high yield. Reduction of pyrroloquinolin-6-ones with hydrogen gas and 10% palladium on carbon or lithium aluminium hydride yielded the dihydropyrroloquinolin-6-ones. Demethylation of pyrroloquinolin-6-ones with 48% hydrobromic acid in glacial acetic acid gave a mixture of the monohydroxy and dihydroxy analogues in high yield. The synthesis of quinolin-4-ones using the Conrad-Limpach method was attempted using three different cyclisation conditions such as Dowtherm A, polyphosphoric acid and a mixture of diphenyl ether and methanesulfonic acid. Quinolin-2-ones such as 4-methyl-3-aryl-, 3,4-diaryl- and 3-aryl-4-benzyl-5,7-dimethoxyquinolin-2-ones could be synthesised from either the N-phenylacetylaniline or the N-trifluoroacetyl aniline strategy. Attempted reduction of the quinolin-2-ones with standard metal hydride reagents was unsuccessful. However reduction was achieved via the conversion of quinolin-2-one to the corresponding 2-chloroquinoline followed by reaction of the chloroquinoline with zinc powder and glacial acetic acid to produce a novel, highly substituted quinoline system. Demethylation was successfully carried out with 48% hydrobromic acid in glacial acetic acid to give the trihydroxyquinolin-2-one in high yield. The reactions of 4-substituted-5,7-dimethoxyquinolin-2-ones and the corresponding 2-chloroquinolines as potential organic intermediates were explored. Facile formylation of both quinolin-2-ones and 2-chloroquinolines was observed under Vilsmeier-Haack conditions while acetylation was successful under Friedel-Crafts conditions using antimony (V) pentachloride as the Lewis acid. Further reaction of 8-formyl-quinolin-2-one with 1,2-diaminobenzene in N,N-dimethylformamide led to the formation of a new 8-(benzimidazolyl)-quinolin-2-one ring system. The quinolin-2-ones exhibited selective electrophilic substitution at the C8 position for a range of reactions. However, an unexpected nitration occurred at the C3 position for the 4-methoxy and 4-phenyl-5,7-dimethoxyquinolin-2-ones with good yields. A series of novel 4,6-hydroxylindoles was successfully synthesised from the corresponding methoxy analogues in high yield using anhydrous aluminium chloride. When 3-(4-bromophenyl)-4,6-dimethoxyindole was reacted with 48% hydrobromic acid in glacial acetic acid a 2,2?-indolylindoline dimer was formed. The 5,7-dihydroxyquinolin-2-ones were similarly synthesised in high yield using anhydrous aluminium chloride in chlorobenzene.

No description available.

No description available.

No description available.

The pyrrolo[3,2,1-ij]quinolin-6-one ring system was synthesised from 3-aryl-4,6-dimethoxyindoles and 2,3-disubstituted-4,6-dimethoxyindoles. The reaction of 4,6-dimethoxyindoles under Friedel-Crafts or Vilsmeier-Haack acylation gave the 2- and 7-indolyldeoxybenzoins in good yield. Cyclisation of 7-indolyldeoxybenzoins with N,N-dimethylformamide dimethyl acetal as a one carbon reagent gave the pyrroloquinolin-6-ones in high yield. Reduction of pyrroloquinolin-6-ones with hydrogen gas and 10% palladium on carbon or lithium aluminium hydride yielded the dihydropyrroloquinolin-6-ones. Demethylation of pyrroloquinolin-6-ones with 48% hydrobromic acid in glacial acetic acid gave a mixture of the monohydroxy and dihydroxy analogues in high yield. The synthesis of quinolin-4-ones using the Conrad-Limpach method was attempted using three different cyclisation conditions such as Dowtherm A, polyphosphoric acid and a mixture of diphenyl ether and methanesulfonic acid. Quinolin-2-ones such as 4-methyl-3-aryl-, 3,4-diaryl- and 3-aryl-4-benzyl-5,7-dimethoxyquinolin-2-ones could be synthesised from either the N-phenylacetylaniline or the N-trifluoroacetyl aniline strategy. Attempted reduction of the quinolin-2-ones with standard metal hydride reagents was unsuccessful. However reduction was achieved via the conversion of quinolin-2-one to the corresponding 2-chloroquinoline followed by reaction of the chloroquinoline with zinc powder and glacial acetic acid to produce a novel, highly substituted quinoline system. Demethylation was successfully carried out with 48% hydrobromic acid in glacial acetic acid to give the trihydroxyquinolin-2-one in high yield. The reactions of 4-substituted-5,7-dimethoxyquinolin-2-ones and the corresponding 2-chloroquinolines as potential organic intermediates were explored. Facile formylation of both quinolin-2-ones and 2-chloroquinolines was observed under Vilsmeier-Haack conditions while acetylation was successful under Friedel-Crafts conditions using antimony (V) pentachloride as the Lewis acid. Further reaction of 8-formyl-quinolin-2-one with 1,2-diaminobenzene in N,N-dimethylformamide led to the formation of a new 8-(benzimidazolyl)-quinolin-2-one ring system. The quinolin-2-ones exhibited selective electrophilic substitution at the C8 position for a range of reactions. However, an unexpected nitration occurred at the C3 position for the 4-methoxy and 4-phenyl-5,7-dimethoxyquinolin-2-ones with good yields. A series of novel 4,6-hydroxylindoles was successfully synthesised from the corresponding methoxy analogues in high yield using anhydrous aluminium chloride. When 3-(4-bromophenyl)-4,6-dimethoxyindole was reacted with 48% hydrobromic acid in glacial acetic acid a 2,2?-indolylindoline dimer was formed. The 5,7-dihydroxyquinolin-2-ones were similarly synthesised in high yield using anhydrous aluminium chloride in chlorobenzene.

An alternate approach to the synthesis of calix[3]indoles has been demonstrated, but further attempted synthetic approaches to calixindoles using new leaving groups led to uncharacterized polymeric products. The synthesis of new 7,7'-diindolylmethane- 2,2'-dicarbaldehydes gives potential for further ligand design and metal complex formation. In addition, 4,6-dimethoxyindole-7- carbaldehydes have been effectively converted to a range of 6-methoxyindole-4,7-diones by Dakin oxidation. Various electrophilic substitution reactions have been performed on the 4,6-dimethoxybenzimidazoles. Formylation, acylation, acid catalyzed addition of formaldehyde and nitration revealed that the activated benzimidazoles are less reactive at the specified C-7 position compared to the analogous indoles. The key starting material for a potential calixbenzimidazole was synthesized by the selenium dioxide oxidation of 2-methyl-7-formyl-4,6-dimethoxybenzimidazole and by oxidative cleavage of 4,6-dimethoxy- 2-styrylbenzimidazole by Lemieux-Johnson reagent followed by reduction. Nevertheless, attempted preparation of calixbenzimidazole from 2-hydroxymethyl-4,6-dimethoxy benzimidazole led to formation of a dibenzimidazolyl ether. The synthesis of some novel activated bisbenzimidazoles has been developed. Furthermore, benzimidazoles were incorporated into new ligand systems which have led to a wide range of acyclic quadridentate neutral metal complexes. Activated benzimidazoles overall illustrate one electron irreversible oxidation to form a radical cation followed by multielectron oxidations. On the other hand, the nickelII and cobaltII benzimidazole metal complexes investigated showed one electron ligand centered reversible reduction. Irreversible radical cation oxidation followed by multielectron oxidation of the metal complexes further demonstrates the rich electrochemical nature of the 4,6-dimethoxybenzimidazoles. Some novel 7-(indol-2-yl)-4,6-dimethoxybenzimidazoles were prepared with indolin-2-one and triflic anhydride and an alternate procedure afforded 2-(4,6-dimethoxyindol-7-yl)-benzimidazoles from activated indoles and 2-benzimidazolinone. Two new isomeric series of 2-substituted-5,7-dimethoxybenzothiazoles and 2-substituted-4,6-dimethoxybenzothiazoles were synthesized via Jacobson cyclization. The two strategically placed electron donating methoxy groups activate these benzothiazoles to undergo various electrophilic substitutions at the 4- and 7- positions respectively.

abstract / Chemistry / Doctoral / Doctor of Philosophy

No description available.

An alternate approach to the synthesis of calix[3]indoles has been demonstrated, but further attempted synthetic approaches to calixindoles using new leaving groups led to uncharacterized polymeric products. The synthesis of new 7,7'-diindolylmethane- 2,2'-dicarbaldehydes gives potential for further ligand design and metal complex formation. In addition, 4,6-dimethoxyindole-7- carbaldehydes have been effectively converted to a range of 6-methoxyindole-4,7-diones by Dakin oxidation. Various electrophilic substitution reactions have been performed on the 4,6-dimethoxybenzimidazoles. Formylation, acylation, acid catalyzed addition of formaldehyde and nitration revealed that the activated benzimidazoles are less reactive at the specified C-7 position compared to the analogous indoles. The key starting material for a potential calixbenzimidazole was synthesized by the selenium dioxide oxidation of 2-methyl-7-formyl-4,6-dimethoxybenzimidazole and by oxidative cleavage of 4,6-dimethoxy- 2-styrylbenzimidazole by Lemieux-Johnson reagent followed by reduction. Nevertheless, attempted preparation of calixbenzimidazole from 2-hydroxymethyl-4,6-dimethoxy benzimidazole led to formation of a dibenzimidazolyl ether. The synthesis of some novel activated bisbenzimidazoles has been developed. Furthermore, benzimidazoles were incorporated into new ligand systems which have led to a wide range of acyclic quadridentate neutral metal complexes. Activated benzimidazoles overall illustrate one electron irreversible oxidation to form a radical cation followed by multielectron oxidations. On the other hand, the nickelII and cobaltII benzimidazole metal complexes investigated showed one electron ligand centered reversible reduction. Irreversible radical cation oxidation followed by multielectron oxidation of the metal complexes further demonstrates the rich electrochemical nature of the 4,6-dimethoxybenzimidazoles. Some novel 7-(indol-2-yl)-4,6-dimethoxybenzimidazoles were prepared with indolin-2-one and triflic anhydride and an alternate procedure afforded 2-(4,6-dimethoxyindol-7-yl)-benzimidazoles from activated indoles and 2-benzimidazolinone. Two new isomeric series of 2-substituted-5,7-dimethoxybenzothiazoles and 2-substituted-4,6-dimethoxybenzothiazoles were synthesized via Jacobson cyclization. The two strategically placed electron donating methoxy groups activate these benzothiazoles to undergo various electrophilic substitutions at the 4- and 7- positions respectively.