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

Authors

Jiliang Hang, University of Nebraska-LincolnFollow

Date of this Version

Spring 4-5-2012

Comments

A DISSERTATION Presented to the Faculty of The Graduate College at the University of Nebraska In Partial Fulfillment of Requirements For the Degree of Doctor of Philosophy, Major: Chemistry, Under the Supervision of Professor Patrick H. Dussault. Lincoln, Nebraska: April, 2012

Copyright (c) 2012 Jiliang Hang

Abstract

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 (¹O₂) is the lowest excited state of oxygen molecule. Due to its special properties, ¹O₂ 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 ¹O₂ lifetime as a major drawback. Therefore, there is a need for ¹O₂ 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 ¹O₂. 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 ¹O₂ via Grob-like process.

Advisor: Patrick H. Dussault