Peterson, John Robert
M.S. (Master of Science)
Department of Chemistry
Podophyllotoxin; Antineoplastic agents
Podophyllotoxin is a molecule with interesting biological activity. Using cinnamic acids as starting materials, some advanced synthetic precursors to this class of anticancer agents were prepared. A new method for synthesis of dicinnamic acid bislactones (2,6- diaryl-3,7-dioxabicyclo[3.3.0]octane-4,8-diones) using cerium(IV) sulfate as an oxidant of cinnamic acid molecules was developed. These bislactones readily underwent rearrangement in methanolic hydrogen chloride to dimethyl 1-aryl-trans-1,2-dihydronaphthalene-2,3-dicarboxylates. The synthetic serviceability of this two-step procedure was determined as a route to the podophyllotoxin carbocyclic skeleton. Another route to the dicinnamic acid bislactones that was explored used manganese(III) acetate as a novel oxidant of potassium methyl malonate. This reaction afforded good yields of dihydro-5-aryl-3,4-di(carboxymethyl)-2(3H)-furanones. The condensation of the latter lactone with benzoyl chloride introduced the second aroyl group and produced a dihydro-3-benzoyl-5-aryl-3,4-di-(carboxymethyl)-2(3H)-furanone. The success of this condensation reaction was considered an important step toward the accomplishment of our goal. Finally, some preliminary studies toward the synthesis of podophyllotoxin using the advanced synthetic intermediates developed above and methyl cinnamates as model compounds were undertaken.
Surjasasmita, Irawan B., "Toward the synthesis of podophyllotoxin" (1988). Graduate Research Theses & Dissertations. 6485.
viii, 57 pages
Northern Illinois University
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