Terpenoid-Alkaloids: Their Biosynthetic Twist of Fate and Total Synthesis

Terpenes and alkaloids are ever-growing classes of natural products that provide new molecular structures that inspire chemists and possess a broad range of biological activity. Terpenoid-alkaloids originate from the same prenyl units that construct terpene skeletons. However, during biosynthesis, a nitrogen atom (or atoms) is introduced in the form of beta-aminoethanol, ethylamine, or methylamine. Nitrogen incorporation can occur either before, during, or after the cyclase phase. The outcome of this unique biosynthesis is the formation of natural products containing unprece-dented structures. These complex structural motifs expose current limitations in organic chemistry, thus providing opportunities for invention. This review focuses on total syntheses of terpenoid-alkaloids and unique issues presented by this class of natural products. More specifically, it examines how these syntheses relate to the way terpenoid-alkaloids are made in Nature. Developments in chemistry that have facilitated these syntheses are emphasized, as well as chemical technology needed to conquer those that evade synthesis.