An organic chemistry approach toward the synthesis of valuable biological compounds: Synthetic progress toward the Palmerolide A subunits, expeditious enyne coupling via alkynes, and development of the next generation of HIV-1 integrase inhibitors

A very rare opportunity has been bestowed into me to work in three different facets of organic chemistry: total synthesis, methodology, and medicinal chemistry. While this intensive experience has certainly assisted me to become a better scientist, there are still many more tasks for me to accomplish. Still, I am confident that my PhD training has prepared me to embark upon the world ahead.;In chapter 1 of this thesis, I will describe the synthetic progress of two subunits, which can be coupled to make a macrolide called Palmerolide A, a bioactive molecule targeting melanoma (i.e. skin cancer). The synthesis of the first subunit is almost complete and it proceeds without significant deviation from the originally proposed scheme. The synthesis of the second subunit is halfway complete. Sensitive functional groups in the second subunit have made it more challenging to complete this piece of Palmerolide A.;A major challenge faced in the preparation of Palmerolide A was the macrocyclization step. Although the boron-Heck reaction did not work successfully for macrocyclization of Palmerolide A, various aspects of this methodology have come to surface. While working on several different coupling reactions for the total synthesis project, I had a chance to explore different aspects of an sp-sp2 boron-Heck coupling reaction, which will be described in detail in Chapter 2.;Chapter 3 details a collaborative project between my advisor and a colleague of his toward the synthesis of the next generation HIV-1 integrase inhibitors. Utilizing focus alteration strategy, an unexpected hit compound has been optimized into a marginally more potent integrase inhibitor.