Spiculoic Acid A, a polyketide natural product, was recently isolated from the marine sponge Plakortis angulospiculatus. The molecule consists of a fused bicyclic framework and its biosynthesis likely involves the formation of a linear tetraene, which undergoes an intramolecular Diels-Alder cyclization. The specific objective of our research is to investigate the mode of action of dehydratase (DH) domains in polyketide biosynthesis. Two conceivable routes may be hypothesized concerning Spiculoic Acid A's biosynthesis. One containing an unusual dehydration mechanism has been proposed that leads to a β,γ-unsaturated thioester intermediate. A more appealing alternative involves a dehydration intermediate that would resemble the normal enzyme catalyzed product. The completed linear polyketide could undergo deprotonation to give an electron-rich extended enolate, a prime substrate for an intramolecular Diels-Alder cyclization. To examine the latter's viability as a biosynthetic precursor its total synthesis is being carried out from phenylacetaldehyde. The outcome of our studies will give insight on the conserved nature and predictability of DH domains and the polyketide synthase enzyme.