Phlegmine A (1), a novel type of Lycopodium alkaloid with a unique skeleton, was isolated from the rare and endangered herbal medicinal plant, Phlegmariurus phlegmaria. Spectroscopic methods and X-ray diffraction analysis were employed to unambiguously elucidate the structure of phlegmine A (1). Furthermore, we realized the asymmetric total synthesis of the natural product phlegmine A (1) in 18 linear steps from commercial ingredients, achieving a 1.3% overall yield. An intramolecular carbene cyclization, dimethyldioxirane (DMDO) enamine oxidation, and Stevens rearrangement were exploited to establish the sterically congested vicinal quaternary centers, and an epimerization/aldol condensation/deacetylation reaction was utilized for the rapid assembly of enone at the final step. During our semisynthesis attempts, a novel transformation was developed to construct alpha-aminoketone from enamine N-oxide. Moreover, the synthetic sample obtained from this work enabled the successful verification of phlegmine A (1) as a new type of highly selective acidsensing ion channel 1a (ASIC1a) inhibitor, which also exerted an in vivo analgesic effect, rendering it a promising lead compound.