Towards the total synthesis of pectenotoxin-4: synthesis of the CDE and F rings

Chapter 1: Introduction This chapter outlines the isolation and structural identification of the pectenotoxin (PTX) family of natural products, as well as their reported biological activity. Finally, the chapter will be concluded with the completed total syntheses of members of the pectentoxin family by Evans and Fujiwara. Chapter 2: Development of a Conjugate Addition-Cyclisation Approach towards the D ring This chapter outlines previous approaches to forming the bicyclic D ring, our proposed approach using a rhodium-catalysed 1,4-addition as the key CâC bond-forming reaction to synthesis PTX-4, and model studies to test the feasibility of this disconnection. Chapter 3: Synthesis of the desired E ring fragment This chapter outlines our current synthesis of the E ring of PTX-4 and the elaborations on the E ring side chain to utilise the rhodium-catalysed 1,4-addition and dihydroxylation/cyclisation sequence as developed in Chapter 2. Chapter 4: Synthesis of the desired F ring fragment This chapter outlines the reoptimisation and scale-up of the F ring synthesis previously published, with modifications to the protecting group strategy employed in preparation for the Julia coupling with the ABCDE fragment in our total synthesis of PTX-4. Chapter 5: Experimental This chapter outlines all the experimental procedures for the reactions described in this thesis, as well as the characterisation data for the compounds synthesised. Chapter 6: Appendices This chapter contains the Mosherâs ester analyses of compounds 282, 331, 463 and 539; as well as nOe analysis of compounds 351, 399, 400, 403, 447, 451 and 469 along with their 1H and 13C NMR spectra. Chapter 7: References This chapter contains the references cited within.