Edible potatoes originated in the Andes and were brought to Europe in the 16th century. Their introduction spurred both the European population growth and economic development. Being the world's fourth-largest food crop, potatoes continue to shape the global economy and world history. Glycoalkaloids are natural insect deterrents generated by potatoes, and are known for their toxic effects as well as potential medicinal utilities. Demissidine, the aglycone of the primary glycoalkaloids, represents one major Solanum alkaloid. Its unique indolizidine framework presents a challenging synthetic target in organic chemistry. Our synthesis of demissidine starts from readily available epiandrosterone and takes advantage of a Lewis acid-mediated fragmentation of a γ-silyloxy-β-hydroxy-α-diazoester; the D-ring of a diazo ester derivative of epiandrosterone was efficiently ruptured to provide an aldehyde tethered ynoate product. In combination with a subsequent azomethine ylide 1,3-dipolar cycloaddition and a transition metal catalyzed oxidation/reduction, the core indolizidine framework of demissidine was successfully prepared in a stereoselective manner. In addition, the syntheses of two amino acids, 5-methylenepipecolic acid and (5S)-5-methylpipecolic acid were explored; they are used for the installation of the α-oriented C25 methyl group on demissidine. The successful preparation of demissidine was supported by NMR analysis of the synthetic compound in comparison with a natural sample. As an efficient and stereoselective synthesis, our efforts toward demissidine illuminate a strategy to indolizidine frameworks that could be applied in the preparation of other polycyclic amine natural products.