Despite an extensive history of natural products total synthesis, devising efficient synthetic strategies for complex secondary metabolites is still intellectually daunting and toilsome. As one means to facilitate the retrosynthetic endeavor, chemists have sought inspiration from the biosynthesis of natural products. We show how structural analysis of biosynthetically relevant natural products and the biosynthetic hypothesis of structurally relevant secondary metabolites can provide hints for the design of synthetic routes. We showcase the viability of this general approach by presenting total syntheses recently completed in our laboratory.1