Scopariusicides, Novel Unsymmetrical Cyclobutanes: Structural Elucidation and Concise Synthesis by a Combination of Intermolecular [2 + 2] Cycloaddition and C–H Functionalization

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 sp3 C–H
bond β-arylation were used synergistically to access the highly
congested unsymmetrical cyclobutane core with four contiguous stereocenters.