Research toward the synthesis of gamma-rubromycin and heliquinomycin
Welton, Thomas Donovan
Doctor of Philosophy
The goal of this project is to develop the strategies necessary to synthesize the rubromycin class of natural products. Synthesis of fully functionalized isocoumarin and naphthoquinone moieties of rubromycin and related compounds are reported. The isocoumarin is formed by a modified condensation reaction of diethyl bromomalonate with a substituted phthalaldehydic acid. The naphthoquinone system is assembled from readily available 2-bromo-5,7,8-trimethoxy-1,4-naphthoquinone that is oxygenated in a copper-catalyzed, addition-elimination reaction with methanol to yield the intermediate 2,5,7,8-tetramethoxy-1,4-naphthoquinone, which is also easily converted to the natural products mompain and 2,7-dimethoxy-1,4-naphthoquinone. A model for the spiroketal core of the rubromycins is also discussed. Multiple coupling strategies of the isocoumarin and naphthoquinone fragments are also discussed. This thesis represents the founding work for this project in the Behar group.
Organic chemistry; Pharmaceutical chemistry