by Tat-hung Tong. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1991. / Includes bibliographical references. / Chapter I. --- Acknowledgements --- p.(1) / Chapter II. --- List of Nomenclatures --- p.(2) / Chapter III. --- Abstract --- p.(4) / Chapter IV. --- Introduction --- p.(5) / Chapter V. --- Results and Discussion --- p.(12) / Chapter (1) --- Synthetic Strategy --- p.(12) / Chapter (2) --- Preparation of onychine (4) --- p.(13) / Chapter (3) --- Preparation of eupolauridine (1) --- p.(25) / Chapter (4) --- "Preparation of benzo-annulated derivative of eupolauridine : 2,3-benzo-l ,6-diazafluoranthene (9)" --- p.(26) / Chapter (5) --- "NMR data interpretation of 2,3-benzo-4-aza-l-methyl-fluoren-9-one (12) and 2,3-benzo-l,6-diazafluoranthene (9)" --- p.(27) / Chapter (6) --- Synthetic study of eilatin (10) --- p.(32) / Chapter VI. --- Conclusion --- p.(36) / Chapter VII. --- Experimental Section --- p.(37) / Chapter VIII. --- References --- p.(56) / Chapter IX. --- NMR Spectra --- p.(58)

A synthetic approach toward the two major fragments of cathedulin K-19, euonyminol (4) and dimethyl cathate (69), was investigated. Synthesis of dimethyl cathate was accomplished in 3 steps starting from 73. Efforts directed towards the synthesis of euonyminol, a highly oxygenated dihydroagarofuran sesquiterpene, was advanced to a stage in which most of the A ring of 4 was completed. Compound 79 was used as a starting material which was obtained from a Diels-Alder reaction of 80 and 81. Subsequent bromination of 79 and elimination of hydrogen bromide afforded 93 in a one-pot operation. A remarkable chemo- and stereoselective reduction of 93 under Luche conditions gave 94 and the latter was epoxidized stereoselectively by m-chloroperbenzoic acid to yield 91. Introduction of an isopropenyl moiety to 91 was accomplished following Liotta's protocol to provide 145. Vanadium catalyzed epoxidation installed the epoxide moiety of 152a with good stereoselectivity. Two approaches towards 4 from the key intermediate 152a were pursued. The first approach entailed the epoxide cascade reaction of 152a. Treatment of 152a with trifluoro- or trichloroacetic acid afforded 165 and 166, respectively, which possessed most of the functionality required for 4. The second route to 178 proceeded in 5 steps from 152a. Treatment of 152a with titanium tetraisopropoxide afforded 168, which was cyclized to 169 under acid catalysis. The diol moiety of 169 was protected as a benzylidene acetal and subsequent hydroxylation following Davis' procedure afforded 171. Stereoselective reduction of 171 using lithium aluminum hydride in the presence of titanium tetraisopropoxide provided 178. / Graduation date: 1994

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

PART I. The preparation of (-)-ibogamine (1) in fourteen steps from benzoquinone and in 10% overall yield is a powerful illustration of the value of the asymmetric Diels-Alder reaction as a starting point in a multistep synthesis. All four cycloadducts, 70, 77, 84 and 96, obtained with the (S)-BINOL-TiCl��� complex were found to have the same absolute configuration. Furthermore, they are in the same enantiomeric series that Mikami observed with 1,4-naphthoquinone using the same catalyst, lending confidence to future stereochemical predictions that may be made with this system. PART II. Three different routes for the synthesis of the hexahydroisoquinoline 98 met obstacles which defeated our approach to koumine. The Diels-Alder reaction of cyclic 1-azadienes 102 and 108 was abandoned due to the lack of reactivity of the dienes. An anionic oxy-Cope rearrangement of the azabicyclo[2.2.2]octane system caused mainly decomposition of the starting materials. Finally, an intramolecular [2+2] photocycloaddition generated "crossed", "straight" and hydroisoquinoline products in varying ratios, depending on the substituent pattern of the substrate, but this approach was not synthetically useful. The results from this last study may be valuable for predicting the regiochemical outcome of certain intramolecular photocycloadditions. / Graduation date: 2003

Graduation date: 1998

Herein is described our synthetic efforts toward the synthesis of (±)-nakadomarin A, a member of the manzamine alkaloids. The first chapter describes the isolation and biological significance of (–)-nakadomarin A. Chapter 2 describes the previous total syntheses as well as other partial syntheses of both (–)-nakadomarin A and its unnatural enantiomer. Chapter 3 discusses our approach to the formation of rings A and B in nakadomarin, as well as the installation of the quaternary center and the regioselective incorporation of a hydrazine moiety. Chapter 4 contains the development of a new methodology for the cleavage of hydrazine N-N bonds situated alpha to a carbonyl functionality. Chapter 5 describes the formation of rings D and E. Chapter 6 consists of experimental details and characterization data for all new compounds. / text

Herein is described our work towards the total synthesis of the marine natural product (±)-chartelline C and the potent antibiotic (-)-platensimycin. Part 1 relates the (±)-chartelline C project. The first chapter reviews (±)-chartelline C’s isolation, biogeneity, and previously reported studies relevant to the area. Chapter 2 tells of our contributions including the development of a convergent, regioselective assembly of an indole-imidazole compound en route to the natural product. Chapter 3 includes the experimental details of this work and the characterization of previously unreported compounds. Part 2 recounts the (-)-platensimycin research project. Chapter 4 discusses the importance of the natural product and the relevant previous research reported. Chapter 5 describes our efforts in this area, culminating in the stereoselective synthesis of an intermediate closely related to a known compound, which was converted to the natural product. Chapter 6 includes the experimental details of this work and the characterization of previously unreported compounds. / text

Herein describes our approaches to the Daphniphyllum alkaloids. Specifically targeted are the recently isolated daphnicyclidins. The first chapter describes the structural diversity and biological properties of this class of alkaloids. Chapter 2 discusses some exploratory chemistry towards the daphnicyclidin fused tricycle. Chapter 3 describes the use of cyclopropanes in synthesis and their use in our ring expansion strategy. Preliminary results on the key cyclopropane ring expansion and the stereoselective quaternary center formation are also discussed. The chemistry concerning the diasteroselective cyclopropanation of a key intermediate and further details concerning the cyclopropane ring expansion are delineated. Chapter 4 contains the experimental details and characterization data for all new reported compounds. / text

(Uncorrected OCR) Abstract of thesis entitled SYNTHETIC STUDIES TOWARDS ISAINDIGOTIDIONE Submitted by Poon Ch Yan for the degree of Doctor of Philosophy at The University of Hong Kong in October 2004 Banlangen (WlWMi), more commonly known in the West as baphicacanthus, is a well-reputed traditional Chinese medicinal herbal drug commonly used to treat ailments such as influenza. It was even prescribed recently in Hong Kong for bolstering immunity against the Severe Acute Respiratory Syndrome (SARS) virus. It is the root of Isatis indigotica Fort. (Cruciferae), a biennial plant found along the valley of the Yangtze River (Changjiang) in central China. Isaindigotidione (I) is an alkaloid isolated from the root of I. indigotica. The organic extracts of this root were found to be active in antiendotoxic tests, indicating that isaindigotidione, like other alkaloids from the root, may possess interesting biological activity. As isaindigotidione is found naturally only in small quantities in I. indigotica, further investigation will only be possible when sufficient quantities are synthesized. Chemically, the structure of isaindigotidione is a novel derivative of indolizino[7,6- cjquinoline (II) found in natural and synthetic products for the first time. To our knowledge, no synthetic studies of this compound or its derivatives have yet been reported, and this thesis describes our efforts to synthesize isaindigotidione and its analogues. The main building blocks of the tetracyclic framework II were L-proline (V) and isatin (VI). The acylation of L-proline derivative VII by BOC-protected isatin was achieved under basic conditions to give phenylglyoxylic amide VIII. It was found that, in the presence of base under reflux, VIII underwent bis-cyclization to afford II. It was noted that four transformations (aldol cyclization, dehydration, acylation, and BOC-deprotection) occurred in a one-pot operation very efficiently to produce excellent yields of II. The isaindigotidione analogues III and IV were also synthesized by the same strategy. Substituents at C-7 were introduced by cuprate addition and a Heck reaction to intermediate IX. Epimerization at the C-7 centre was found to occur under the bis-cyclization conditions, and analogues III and IV were obtained as epimeric mixtures. Unfortunately, it was discovered upon extensive investigation that these organometallic conjugate addition reactions did not lend themselves to the addition of the 2,6-dimethoxy-l-phenol moiety to IX and its derivatives, which this retroanalysis indicates is required for the synthesis of isaindigotidione. Several factors were found to deter the addition of the desired substituent, including the steric demands of IX, and the low reactivity of phenyl and aryl organometallic reagents. O. ^N�''/ i H ^O OMe OH OMe II ,NL !""'H ^CH3 i H ^O III IV COOH "N H O^N H VI H .0 OMe OMe � ^ BOC f OMe VII VIII IX / abstract / toc / Chemistry / Doctoral / Doctor of Philosophy