Cyclopamine (1), first isolated from Veratrum californicum (California corn lily) , is a notable member of the Veratrum alkaloid family (Figure ). 2 It is known ex post facto for inducing the cyclopia birth defect in sheep, where the affected new-born lambs only had one eye and were reminiscent of the cyclops from Greek mythology. Studies from Beachy et al. revealed that cyclopamine is a potent inhibitor of the highly conserved hedgehog signaling pathway, which is critical for the correct differentiation and symmetry development of embryos. Despite its known decomposition pathway leading to veratramine (3) and other byproducts under acidic conditions 5 , cyclopamine has been recognized as a promising anti-cancer agent and numerous medicinal analogs have been reported to date, most notably saridegib (4) which was prepared semisynthetically. The intricate structures of Veratrum alkaloids have piqued the interest of synthetic chemists for years. 7 With respect to cyclopamine, the rare C-nor-D-homo steroid skeleton is further complicated by the fully substituted, spirocyclic THF motif, the unique trans-6,5 EF ring system, and the central tetrasubstituted olefin, all of which posed unique challenges to its synthesis. A pioneering synthesis of the closely related jervine (2) by Masamune et al. involves an 18-step sequence starting from the advanced intermediate 6, which in turn must be prepared in 25 steps from Hagemann's ester or obtained from degradation of hecogenin. 7a More recently in 2009, Giannis et al. disclosed an elegant semi-synthesis of cyclopamine in 20 steps from dehydroepiandrosterone (5), featuring a biomimetic 1,2skeletal rearrangement to construct the C-nor-D-homo steroid scaffold. 7h Multiple progress-towards studies of jervine or cyclopamine have also been reported to date. 8 This Communication discloses a convergent and enantioselective total synthesis of 1 with a 15-step LLS.