Author : Jiehui Pan
Publisher : Open Dissertation Press
ISBN 13 : 9781361426166
Total Pages : pages
Book Rating : 4.4/5 (261 download)
Book Synopsis Transition Metal Catalyzed Cyclization and Synthesis of Triptolide Analogs by : Jiehui Pan
Download or read book Transition Metal Catalyzed Cyclization and Synthesis of Triptolide Analogs written by Jiehui Pan and published by Open Dissertation Press. This book was released on 2017-01-27 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "Transition Metal Catalyzed Cyclization and Synthesis of Triptolide Analogs" by Jiehui, Pan, 潘杰輝, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled TRANSITION METAL CATALYZED CYCLIZATION AND SYNTHESIS OF TRIPTOLIDE ANALOGS Submitted by Pan Jiehui for the Degree of Doctor of Philosophy at The University of Hong Kong in March 2006 (-)-Triptonide, (-)-triptolide, and 16-hydroxytriptolide are bioactive natural product, isolated from the Chinese medicinal plant Tripterygium wilfordii Hook. F. (Lei Gong Teng). They show potent immunosuppressive, antileukemic, and antifertile activities. However, their mechanisms of actions still remain elusive, and only limited structure-activity relationship studies of triptolide and its analogs have been carried out. I have successfully synthesized bioactive alkyne-derived triptolide probe and azide functionalized fluorophore tags, which were designed for identifying the receptors of triptolide by using the click chemistry method. A model reaction simulating the cycloaddition between the bioactive triptolide probe and rhodamine tag has been successfully accomplished, which could be applied in the search for the receptors of triptolide. Synthetic studies of triptolide analogs could provide new methods to prepare analogs containing moieties different from the original triptolide molecule, and possibly enable its curative effects to be distinguished from its toxic effects. Two efficient cross-coupling methods including the Heck reaction and the Sonogashira coupling have been utilized for the introduction of the C-13 side chain of triptolide analogs. These protocols provide new ways to modify the triptolide molecule at the C-13 position in addition to the Claisen rearrangement. Several novel dimeric triptolide analogs with different functionalities at the C-13 position have been prepared. The exploration of transition metal-catalyzed cyclization reactions has been at the frontier of organic synthesis. I have prepared several sterically bulky N, N'-disubstituted cyclic thiourea-gold(I) complexes. The crystal structures of the complexes reveal the different coordination nature of sulphur in these complexes in the solid state. In solution, a ligand scrambling reaction has been observed with the N, N'-dialkyl cyclic thiourea ligands. Useful information about the equilibrium of ligand scrambling reaction has been obtained from the H NMR experiments. I have used bulky N, N'-disubstituted cyclic thioureas as effective ligands for the Au(I)-catalyzed carbocyclization of 1,3-dicarbonyl compounds with alkynes. The reactions can be readily conducted with a low catalyst loading, short reaction time in an "open flask" system and in high yields. In addition, I have demonstrated an application of the bulky N, N'-disubstituted cyclic thiourea-Au(I) complexes in the cycloisomerization of acetylenic 1,3-dicarbonyl compounds to form γ-lactones and γ-lactams. These reactions can be readily conducted with low catalytic loading in an "open flask" system and provide a new method to generate γ-lactones and γ-lactams. DOI: 10.5353/th_b3776596 Subjects: Ring formation (Chemistry) Bioactive compounds - Synthesis Transition metal catalysts
