The structurally related PM-94128 and Ajudazols A and B exhibit differing biological activities but share the isocoumarin core structure. PM-94128 belongs to a large family of compounds known as the aminodihydroisocoumarins and was isolated in 1997. It has been shown to be an inhibitor of DNA and RNA synthesis and have potent cytotoxic activity in vivo. The Ajudazols A and B were isolated in 2004 and have antifungal activity against several important food spoilers. The work that follows details the design and development of a novel method for the generation of the isocoumarin core from isobenzofuran utilizing the Achmatowicz rearrangement of a-hydroxyisobenzofurans. Spirocyclic pyrans such as Polymaxenolide are structurally complex molecules, containing large amounts of functionality. The biological activity of Polymaxenolide is unknown and there have been no total syntheses reported to date.