A unified approach to mitomycinoids: Application of a novel ene-like reaction
Lovett, Dennis Paul
Ciufolini, Marco A.
Doctor of Philosophy
A practical synthesis of the powerful antitumor agents, mitomycin C and FR900482, remains an elusive goal to this date. These substances may be thought to arise from suitably functionalized benzazocinones as retrosynthetic intermediates. The key to a unified strategy for the synthesis of all mitomycinods is thus a concise, efficient route to a common benzazocenone, which requires appropriate substituents on the aromatic ring as dictated by the specific target molecule. The preparation of medium ring heterocycles of this type is troublesome. The research described herein has been directed toward the development of a practical solution to this problem. We describe the application of our novel ene-like reaction for the construction of benzazocinone intermediates as well as research towards various methods to transform them into suitable intermediates for the total synthesis of mitomycinoids. We also developed an efficient method for construction of properly functionalized aldehydes for our ene-like reaction, as well as the synthesis of an achiral diol which can be desymmetrized for use in an enantiocontrolled synthesis. The information accumulated from these experiments will, undoubtedly, be helpful in completion of the total synthesis of FR900482 and other mitomycinoids, which continues in our laboratories.
Organic chemistry; Pharmaceutical chemistry