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Natural products have always been a valuable source for scientists who try to identify molecules possessing unique bioactivities and functions. Due to the rapid evolution of synthetic methodologies and strategies over the past two centuries, the field of natural product total synthesis has advanced to an awe-inspiring level. Meanwhile, a number of new concepts to guide the development of next generation total synthesis have emerged. One of the most evoking terms is divergent synthesis, which is also known as common intermediate-based synthesis. It aims to efficiently assemble a collection of structurally distinct natural products, instead of one single molecule, via a well-designed common synthetic intermediate. Such process is of particular significance for research in the pharmaceutical industry, material science, and agricultural industry, where high level of molecular diversity is demanded. This dissertation describes our efforts to utilize a divergent approach in completing a range of natural products in the Laurencia ethers and the manginoid family. Thus, Chapter 1 will provide a brief overview of divergent total synthesis and introduce the general challenges and opportunities in this area. Three previous successful works using this principle are discussed to showcase how the common intermediates of their choice necessitate innovation of new chemical tools. Moreover, these examples will also highlight how the development of novel strategies could lead to a versatile common intermediate and synthetic route with high degree of divergence. Chapter 2 will detail our efforts to synthesize five members of the Laurencia ethers encompassing two distinct 8-menbered ring motifs from a common intermediate. In this work, we will describe a new variant of BDSB-induced ring expansion with an enyne substrate, which could fashion the 8-membered ring with the bromoallene appendage present in microcladallenes. Meanwhile, we will also demonstrate that the BDSB-induced ring expansions (with an alkene or enyne) could proceed in the presence of an additional ring attached to the tetrahydrofuran core. These results, along with the completion of our five targets, will showcase the power of common intermediate-based strategy in the synthesis of Laurencia natural products. Finally, in Chapter 3, we will propose a divergent synthesis towards members of the manginoid family and a range of natural products containing a similar trans-hydrindane system. Then the first total synthesis of manginoid A via a number of highly chemo- and stereo-selective operations based on the designed common intermediate will be presented. The establishment of a concise and robust preparation of the plausible common intermediate lays the foundation for our global approach towards all other target molecules.




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