The total synthesis and synthetic efforts towards various diterpene and polyketide natural products is described. A straightforward and robust synthesis of the furanocembranoid bipinnatin J was developed that also resulted in confirmation of the absolute stereochemistry of the natural product. Several biosynthetic relationships between bipinnatin J and other furanocembranoid diterpenes were investigated. An unprecedented, transannular 1,3-dipolar cycloaddition was utilized to access the pentacyclic natural product intricarene from bipinnatin J. In addition, selective reductions and oxidations were employed to give rubifolide, isoepilophodione B, coralloidolide A, and coralloidolide E. Significant progress was made toward the related furanocembranoid plumarellide. A key, transannular Diels-Alder cycloaddition is envisioned to make the pentacyclic framework of plumarellide.

The total synthesis of the polyketide macrolactone archazolid B was accomplished. Three linear subunits were assembled utilizing several modern transition-metal-catalyzed reactions. A relay ring-closing metathesis strategy was exploited to create the 24-membered macrocycle of the natural product. Finally, considerable progress was made toward members of the azaphilone family of polyketide natural products, including S-15183a and mitorubrinic acid. Two different strategies were investigated to access the isochromene core shared by all the natural products.