Synthetic Studies Toward the Total Synthesis of Maklamicin and Related Spirotetronate Polyketides
Spirotetronate polyketides are naturally occurring natural products that are highlighted by their complex structures and intruiging biological activities. Chapter 1 emphasizes the importance of this class of natural products from their synthetic endeavors to their molecular targets as cancer therapeutics. Chapter 2 discusses the synthesis of the decalin moiety for the class of spirotetronate polyketides. The synthesis is highlighted by an intramolecular Diels-Alder reaction (IMDA) that proceeds through an energetically unfavored endo-axial transition state. Chapter 3 examines synthetic efforts toward the total synthesis of maklamicin and the difficulties in the synthesis of spirotetronates polyketides in the laboratory. Chapter 4 elaborates upon a general synthetic strategy towards the synthesis of this class of natural products addressing the main struggles faced towards the total synthesis of maklamicin. This strategy also opens a general strategy to potentially synthesize spirotetronate polyketides with varying sizes of the macrocyclic motif.