I. Synthesis of β-Sitosterol and Phytosterol Esters; II. New Methodology for Singlet Oxygen Generation from 1,1-Dihydroperoxides

Phytosterols are steroid compounds structurally similar with cholesterol and vary in the nature of carbon side chain. β-Sitosterol is commercially available in preparative amount only as mixtures with other phytosterols. New semipreparative synthesis of pure β-sitosterol and sidechain-modified phytosterols is discussed in this dissertation. This new synthesis is achieved via a temporary masking of the stigmasterol 5,6-alkene as an epoxide. Following performance of the desired modification, the alkene is regenerated through a mild deoxygenation. Preparation of phytosterol esters for cholesterol metabolism study is also discussed in this dissertation. Singlet oxygen (1 O 2) is the lowest excited state of oxygen molecule. Due to its special properties, 1 O 2 has been widely used as the oxidant in chemistry, biology, and medicine. In the past decades, two major generation methods have been developed, photosensitization and chemical generation. However, most of the reported chemical generations require the water-rich media, which is associated with short 1 O 2 lifetime as a major drawback. Therefore, there is a need for 1 O 2 generation from organic solvents. The investigation of fragmentation of monoactivated derivatives of 1,1-dihydroperoxides is discussed in this dissertation. This previously unobserved fragmentation can be conducted in various organic solvents and generate high yield of 1 O 2. This reaction is general for a range of skeletal frameworks and activating groups, and can be applied directly to 1,1-dihydroperoxides via in situ activation. Kinetic and mechanistic investigation suggests it involving rate-limiting formation of a peroxyanion, which decompose to generate 1 O 2 via Grob-like process. i Acknowledgements Foremost, I would like to thank my advisor, Professor Patrick Dussault, for his continuous support of my Ph.D study and research. His guidance helped me in all the time of research and writing of this thesis. I am very lucky to have such a great advisor. for the help and useful discussions in my research projects. Finally, I would like to thank my parents, Zhengqing Hang and Aiqin Yu, and my wife, Lili Lou for their love and understanding. They always supported me in all my pursuits. Without their encouragement it would be impossible for me to finish my study. I would also like to thank my son Kevin for bringing me so much fun. ii Table of Contents Chapter 1 Synthesis of pure β-sitosterol and other phytosterols 1.1 Introduction 1 1.2 Results and discussion 5 Stigmasterol hydrogenation with Raney Nickel 5 Stigmasterol hydrogenation with Rieke …