Degree Type

Dissertation

Date of Award

1987

Degree Name

Doctor of Philosophy

Department

Chemistry

First Advisor

George A. Kraus

Abstract

The total synthesis of anthracycline antibiotics is believed to be among the most promising subjects for the development of new drugs for the treatment of human cancers. It was the purpose of this research to develop novel synthetic approaches to 11-deoxyanthracyclines;Part I describes the successful total synthesis of 11-deoxydaunomycinone and 4-demethoxy 11-deoxydaunomycinone by a sequence involving an acyl transfer reaction followed by a tandem Claisen-Diels-Alder reaction. Oxidation of the resulting [beta]-diketone with DDQ provides the tricyclic naphthoquinone which contains functionality well suited for the synthesis of 11-deoxyanthracyclines with different D ring substitution. Subsequent Diels-Alder reaction with either 1-methoxy-1,3-cyclohexadiene or 1-trimethylsilyloxy-1,3-butadiene produces adducts which can be transformed into 11-deoxydaunomycinone and its 4-demethoxy analogue;Part II describes the direct and operationally convenient synthesis of linear polycyclic quinones via the Diels-Alder reaction of quinone sulfoxides. The mild conditions required to effect both Diels-Alder reaction and elimination of phenylsulfinic acid represent a useful feature of this reaction. The utility of this method is demonstrated further by the regiospecific preparation of the tricyclic quinone sulfoxide and its use for the construction of the tetracyclic framework of the 11-deoxyanthracycline nucleus.

DOI

https://doi.org/10.31274/rtd-180813-11112

Publisher

Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/

Copyright Owner

Soon Hyung Woo

Language

en

Proquest ID

AAI8805154

File Format

application/pdf

File Size

137 pages

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