Title

Part I: Synthesis of novel dihydroceramides from the dental pathogen Porphyromonas gingivalis. Part II: The use of poly(3,4-ethylenedioxythiophene) (PEDOT) as a chemical reagent

Date of Completion

January 2008

Keywords

Chemistry, Organic

Degree

Ph.D.

Abstract

Part I. Porphyromonas gingivalis is a suspected periodontal pathogen that produces two classes of novel phosphatidyl dihydroceramides, with biological activity ranging from pro-inflammatory agents to compounds that induce bone degeneration and compounds that appear to trigger multiple sclerosis symptoms in mice. GCMS and NMR analysis of the extracts suggested these lipids are in fact dihydroceramides that are characterized by isobranched, odd-carbon chains, and β-hydroxyl functionality. The dihydrosphinganine portion of the dihydroceramide contains either a C17 or C19 isobranched alkyl chain or a C18 straight alkyl chain. Attached to the dihydrosphinganine through the amide linkage is a C19 isobranched β-hydroxy fatty acid. We have synthesized several of these punitive pieces and verified their presence in the complex lipid mixture. Apart from the synthesis and verification of the structure, our work is focused on determining the absolute and relative stereochemistry of the most active dihydroceramides. Due to the complexity of the lipid extracts, we have not been able to isolate individual dihydroceramide lipid components in pure form, directly from P. gingivalis by using chromatographic methods, making their synthesis essential for both structural verification and determination of the stereochemistry of the stereogenic centers. ^ Part II. Conducting polymers are rarely thought of as chemical reagents that promote chemical transformations. Poly(3,4-ethylenedioxythiophene) is a conductive polymer that is prepared electrochemically with a triflate counterion. Chemical reactions induced by PEDOT alone have not been reported prior to our work. The commercial importance of PEDOT, along with the ease of preparation and handling, stability in air and solvents, and its conductive properties, led us to choose it for our studies. ^ In our work, PEDOT induces chemical reactions of alcohols without overoxidation, without incorporating reactive functional groups, and without adding additional reagents. With this in mind, we decided to study the chemistry occurring between PEDOT and alcohol derivatives, specifically benzylic or allyic alcohols and sorbitol and its derivatives. The purpose of our work is to show that by using PEDOT, simple acid-catalyzed chemical transformations can be done more cleanly and efficiently within a neutral medium having water be the only by-product. ^