Huperserratines A (1) and B (2), two novel macrocyclic Lycopodium alkaloids, possess an aza-12-membered ring. Here, we describe the first total synthesis of these two natural products in 12 steps. Key elements of the synthesis include the Suzuki-Miyaura coupling, the Hosomi-Sakurai reaction, ring-closing metathesis, dihydroxylation, and the Swern oxidation. A gram-scale ring-closing metathesis was pivotal in forging the challenging aza-12-membered ring. This total synthesis would enable future studies on the structure-activity relationship of 1 and 2. © 2022 The Royal Society of Chemistry.