Evaluation of methods to generate substituted tetrahydroxanthone ring systems : DMAP promoted cycloisomerizations

This dissertation presents investigations on the synthesis of polyoxygenated tetrahydroxanthone ring systems. Chapter 1 provides a brief overview of the family of naturally occurring compounds called xanthones. The classification, isolation, biological properties and the synthetic approaches to this family of compounds is included. Because the work of this dissertation was inspired by the tetrahydroxanthone unit embedded in simaomicin α (1.1), a detailed review of the synthetic methods available to access tetrahydroxanthone units is presented. Chapter 2 describes eight synthetic approaches that were investigated to construct substituted tetrahydroxanthones. A stereospecific intramolecular [3+2] dipolar cycloaddition of nitrile oxides resulted in the synthesis of novel fused tetracyclic isoxazolines, tetracyclic isoxazoles, and aminotetrahydroxanthones. An intramolecular hydroacylation promoted by N-heterocyclic carbenes produced substituted tetrahydroxanthones and hexahydroxanthones. Chapter 3 describes the successful synthesis of polyoxygenated tetrahydroxanthones through a 4-dimethyl- aminopyridine-promoted cycloisomerization of o-alkynoylphenol derivatives. It is proposed that the cycloi- somerization is initiated by the 1,4-addition of DMAP, followed by either a Morita-Baylis-Hillman-type aldol reaction, or deprotonation of the phenol. However, the actual mechanism remains unknown. The cycloisomerization of o-alkynoylphenol derivatives was useful in the synthesis of 1,4,5-trioxygenated or 1,5- dioxygenated tetrahydroxanthones with variable substituents at position 7. The diastereoselectivity of the reaction modestly favoured the trans-isomer.Science, Faculty ofChemistry, Department ofGraduat