Rupestine G is a guaipyridine sesquiterpene alkaloid isolated from Artemisia mpestris L. The total synthesis of rupestine G and its epimers was accomplished employing a Suzuki reaction to build a terminal dime moiety. The diene was further elaborated into the desired guaipyridine structure by a ring closing metathesis reaction. Over all, rupestine G and its three epimers were obtained as a mixture in a sequence of nine linear steps with 18.9% yield. Rupestine G and its optically pure isomers were isolated by chiral preparative HPLC and fully characterized by H-1,C-13 HRMS, optical rotation value, and experimental and calculated electronic circular dichroism spectroscopy.