Part I. Total synthesis of artochamins H, I, J, and K. Part II. Synthesis of the QRSTU domain of maitotoxin and its 85-epi and 86-epi-diastereoisomers

This thesis is separated into two parts: the total synthesis of artochamins F, H, I, and J, and the synthesis of the QRSTU domain of maitotoxin and its 85-epi- and 86-epi-diastereoisomers. The total synthesis of the prenylated tetracycles H--J via a cascade sequence involving two consecutive Clasien rearrangements followed by the key cyclobutane-forming process through a common intermediate, such as artochamin F, is described in Chapter 1. Additionally, potential mechanisms by which the tetracyclic core of the natural products is forged and the role of Ph3PO is discussed in detail; leading to an intriguing ionic mechanism.;Chapter 2 and 3 focuses on the work towards the QRSTU domain of maitotoxin, the only extended segment of the molecule that remained elusive to synthesis until now. Chapter 2 provides an introduction into polyethers and highlights the isolation, biosynthetic hypothesis, structure determination, and biological activity of maitotoxin. Moreover, the first synthetic strategy, involving late stage closure of the R ring, towards the pentacyclic QRSTU fragment is presented. The challenges encountered in introducing the five angular methyl groups present in the ring system are discussed and intelligence gathering from the first synthetic strategy toward the QRSTU ring system leads to the final, convergent and flexible route to the QRSTU pentacycle (Chapter 3) and two of its diastereoisomers, 85-epi-QRSTU and 86- epi-QRSTU ring system. 13C NMR spectroscopic analysis of the synthesized QRSTU domain and its two diastereoisomers allowed for comparison of their 13C chemical shifts with that of natural maitotoxin, providing strong support for the originally assigned structure of the QRSTU domain of the natural product.