Inspired by the common skeletal motifs of Ca<sup>2+</sup>-ATPases inhibitors involving artemisinin and transtaganolide D, small molecule collections with the three-dimensional structural diversity of tricyclic systems were designed and expeditiously synthesized (4−5 steps). A synthetic strategy featuring stereochemical diversification of ring-junctions and control of cyclization modes was devised to access varied molecular architectures in a systematic fashion.