The amphidinolides are macrolide natural products isolated from marine dinoflagellates of the genus Amphidinium and most of them display potent cytotoxic activities in vitro. Amphidinolides C-C3, F and T1-5 represent attractive synthetic targets due to a combination of potent bioactivity and complex molecular architecture. This thesis describes the total syntheses of amphidinolides T1, T3 and T4, and the preparation of the C1-C17 fragment of amphidinolides C and F. Concise and high-yielding total syntheses of amphidinolides T1, T3, and T4 have been completed using an alkynyl macrolactone as a common late-stage intermediate. The α-hydroxy ketone motif was installed by sequential alkyne hydrosilylation, epoxidation, and Fleming–Tamao oxidation. A tandem oxonium ylide formation [2,3]-sigmatropic rearrangement reaction was used to construct the trisubstituted tetrahydrofuran core found within the natural products. The C1-C17 fragment of amphidinolides C, C2, C3 and F was synthesised employing [2,3]-sigmatropic rearrangement of an oxonium ylide generated by decomposition of 1-sulfonyl-triazole to construct the trisubstituted tetrahydrofuran ring found in the natural products. The two main segments were conjoined using a Stille cross-coupling reaction that allowed simultaneous installation of the isomerization-prone 1,3-diene unit.