The synthesis of compounds for the treatment of current health concerns : potent anti-HIV agents and cholesterol-lowering functional food products

Author

Anthony Michael Condo

Date of Award

12-2001

Degree Type

Thesis

Degree Name

Master of Science

Major

Chemistry

Major Professor

Linda J. Magid

Committee Members

Elizabeth E. Howell, Ronald M. Magid

Abstract

In an ongoing effort to develop pharmaceutically active compounds for use in treating patients with HIV, we have investigated a series of 3-aryl-2-methyl-2,3- dihydrobenzo[d]isothiazole 1,1-dioxides. Some of these compounds, commonly known as "sultams", have shown potent activity in in vitro screens as non-nucleoside reverse transcriptase inhibitors (NNRTIs) of HIV-1 (EC₅₀'s in the submicromolar range). The compounds that have been identified as the most potent in the biological screens have been substituted analogs at the 3-position of the 0 ring. In light of these results, we have extended our studies to include an investigation of the effects of substitution at the 3-position on the biological activity. The synthesis of a number of analogs bearing a range of functional groups at this position has been accomplished. The ability of phytosterols and phytostanols to lower serum low-density lipoprotein-cholesterol (LDL-C) levels in humans is well documented. Commercially, "functional foods" such as Benecol® and Take Control®, contain fatty acid esters of both phytosterols and phytostanols, respectively. The purpose of the esterification is to improve the solubility of the otherwise insoluble free sterol or stanol. These esters are hydrolyzed in the intestine to the proposed physiologically active sterol or stanol. The aim of this project was to synthesize multi-gram quantities of these fatty acid esters to be used in an appropriate hamster-feeding study by our USDA collaborators. We were able to synthesize these esters under mild laboratory conditions which we thought to be more amenable to large-scale production and reproducibility than that which was previously reported in the literature.

Recommended Citation

Condo, Anthony Michael, "The synthesis of compounds for the treatment of current health concerns : potent anti-HIV agents and cholesterol-lowering functional food products. " Master's Thesis, University of Tennessee, 2001.
https://trace.tennessee.edu/utk_gradthes/9595