Publication Date

1988

Document Type

Dissertation/Thesis

First Advisor

Peterson, John Robert

Degree Name

M.S. (Master of Science)

Department

Department of Chemistry

LCSH

Podophyllotoxin||Antineoplastic agents

Abstract

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.

Comments

Bibliography: pages [52]-57.

Extent

viii, 57 pages

Language

eng

Publisher

Northern Illinois University

Rights Statement

In Copyright

Rights Statement 2

NIU theses are protected by copyright. They may be viewed from Huskie Commons for any purpose, but reproduction or distribution in any format is prohibited without the written permission of the authors.

Media Type

Text

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