Scopariusicides A (1) and B (2), two novel immunosuppressive unsymmetrical cyclobutane derivatives, were isolated from the aerial parts of Isodon scoparius. Moreover, based on the results of phytochemical investigation, a concise stereocontrolled synthesis of scopariusicide A and its analogues with enhanced biological activities was efficiently achieved using the main diterpenoid (3) isolated from this plant as a readily available starting material. A crossed intermolecular [2 + 2] photocycloaddition and a Pd-catalyzed sp(3) C-H bond β-arylation were used synergistically to access the highly congested unsymmetrical cyclobutane core with four contiguous stereocenters.

Twenty-one structurally diverse diterpenoids (1–21), wherein 1, 2, and 4 represented unprecedented architectures, were isolated from Isodon pharicus.