Gamma-butyrolactones (GBLs) are signaling molecules produced by Streptomyces that play a key role in secondary metabolite production. Secondary metabolites, also known as natural products, have been used extensively in medicine and agriculture due to their bioactive properties. Genomic sequencing of the biosynthetic gene clusters (BGCs) from Streptomyces shows that only a small fraction of their secondary metabolites has been discovered. Activation of these silent BGCs has reinvigorated natural products chemistry as researchers become aware of the potential reservoir of novel lead compounds that remain unmined. One such GBL produced by Streptomyces is avenolide, responsible for activating production of avermectin, an anti-parasitic drug with over $850 million annual sales. In the work presented here, progress was made towards accessing the molecule avenolide in a synthesis commendable to derivatization with the aim of creating a library of avenolide-like molecules that could potentially “unlock” cryptic biosynthetic gene clusters and lead to the discovery of new bioactive secondary metabolites.

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

Plakortide E (85), which is isolated from the Jamaican marine sponge Plakortis halichondrioides, contains a five-membered peroxide ring, with the oxygen atoms are linked to tertiary C4 and C6 centers.34,57 In this thesis, the total synthesis of plakortide E (85) is described. A novel palladium-catalyzed approach towards 1,2-dioxolanes has been developed. A lipase-catalyzed kinetic resolution was employed to provide optically pure 1,2-dioxolane central cores. Coupling of the central cores and side chains was achieved by a Negishi reaction. All four isomeric structures of plakortide E methyl ester, namely, 86a-d were synthesized, and one of these molecules, 86d proved to be natural plakortide E methyl ester on the basis of 1H, 13C NMR spectra and specific rotation. With plakortide E methyl ester (4S,6R, 10R)-(-)- cis-(86d) and its other three isomers in hand, we successfully converted them into plakortone B (3S,4S,6 R,10R)-(87a), and its isomers ent-87a, 87b and ent-87b via an intramolecular oxa-Michael addition/lactonization cascade reaction. Saponification converted 1,2-dioxolane 86d into plakortide E (85a) whose absolute configuration (4S,6 R,10R) was confirmed by comparison of spectral and physical data with those previously reported.35b / Sun, Xiaoyu. / Adviser: Henry N. C. Wong. / Source: Dissertation Abstracts International, Volume: 73-06, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 183-195). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

by Andy Kwong Shun Tse. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 53-57). / ACKNOWLEDGMENTS --- p.i / ABBREVIATIONS --- p.ii / ABSTRACT --- p.iv / CONTENTS --- p.v / Chapter Part 1: --- Serendipitous Synthesis of Cobalt(III) and Rhodium (III) Porphyrin-phosphoryls / Chapter I. --- INTRODUCTION --- p.1 / Chapter II. --- RESULTS AND DISCUSSIONS --- p.6 / Chapter III. --- CONCLUSION --- p.28 / Chapter Part 2: --- Synthesis of Rhodium(III) Porphyrin-silyls / Chapter I. --- INTRODUCTION --- p.29 / Chapter II. --- RESULTS AND DISCUSSIONS --- p.32 / Chapter III. --- CONCLUSION --- p.41 / EXPERIMENTAL --- p.42 / REFERENCES --- p.53 / APPENDIX I-III --- p.58 / LIST OF SPECTRA --- p.61 / SPECTRA --- p.62

by Michael Tsang Ming Choi. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves 85-90). / Abstracts in English and Chinese. / ACKNOWLEDGMENT --- p.i / TABLE OF CONTENTS --- p.ii / LIST OF FIGURES --- p.iv / LIST OF TABLES --- p.vi / ABBREVIATIONS --- p.vii / ABSTRACT --- p.viii / 摘要 --- p.ix / Chapter PART I. --- "SYNTHESIS, SPECTROSCOPIC PROPERTIES AND AGGREGATION BEHAVIOR OF SUBSTITUTED 2,3- NAPHTHALOCYANINES" / Chapter 1 --- INTRODUCTION --- p.2 / Chapter 1.1 --- "Synthesis of 2,3 -Naphthalocyanines" --- p.6 / Chapter 1.2 --- Aggregation Phenomena of Phthalocyanines --- p.14 / Chapter 1.3 --- Phthalocyanines with Crown Ether Voids --- p.20 / Chapter 2 --- RESULTS AND DISCUSSION --- p.26 / Chapter 2.1 --- "Synthesis of Substituted 2,3-Naphthalocyanines" --- p.26 / Chapter 2.2 --- Synthesis of Substituted Phthalocyanines --- p.29 / Chapter 2.3 --- "Characterization of 2,3-Naphthalocyanines and Phthalocyanines" --- p.31 / Chapter 2.4 --- "Aggregation Behavior of Octasubstituted 2,3-Naphthalocyanines and Phthalocyanines" --- p.34 / Chapter 2.5 --- Liquid Crystalline Properties of64 --- p.43 / Chapter 2.6 --- "Synthesis of a Crown Ether-Substituted 2,3-Naphthalocyanine" --- p.45 / Chapter 2.7 --- Conclusion --- p.48 / Chapter 3 --- EXPERIMENTAL SECTION --- p.49 / Chapter 3.1 --- Materials --- p.49 / Chapter 3.2 --- Physical Measurements --- p.49 / Chapter 3.3 --- General Procedure for the Preparation of Dinitriles --- p.50 / Chapter 3.4 --- General Procedure for the Cyclization of Dinitriles --- p.53 / Chapter PART II. --- SYNTHETIC STUDIES OF SUBSTITUTED DICYANO-ANTHRACENES AND TETRACENES / Chapter 1 --- INTRODUCTION --- p.57 / Chapter 2 --- RESULTS AND DISCUSSION --- p.63 / Chapter 2.1 --- Synthesis of Substituted Anthracenes --- p.63 / Chapter 2.2 --- Synthesis of Substituted Tetracenes --- p.72 / Chapter 2.3 --- Conclusion --- p.77 / Chapter 3 --- EXPERIMENTAL SECTION --- p.78 / REFERENCES --- p.85 / Chapter APPENDIX --- Crystallographic data of dimer of anthracene118 --- p.91

Chan Kin Fai. / "April 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 151-157). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Graduation date: 1999

Graduation date: 1995

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