Introduction. (-)-Colchicine (1, Figure ) is one of the world's oldest known medicines, dating back to at least ancient Egypt, when its natural product source, the autumn crocus, was used for treatment of inflammation. In more recent times, the pure form of colchicine has been used as an FDA-approved drug most closely associated with gout, but also used for prevention of pericarditis and familial Mediterranean fever, 2 and there is growing interest in other applications. For example, just this year the FDA approved colchicine for use in the prevention of cardiovascular disease. Colchicine's broad value is generally tied to its microtubule destabilizing activity, 5 which is the mechanism through which many of the most important and widely used chemotherapeutics work. While colchicine is not currently used clinically as a chemotherapeutic due to its high toxicity, there is high active interest in the development of anti-cancer agents that target the colchicine-binding site of tubulin. (-)-Colchicine's tubulin-binding is directly related to its axially chiral AC ring, which is thermodynamically set into the preferred tubulin-binding aR form by nearby point chirality on its 7-membered B ring. 7 While (+)-colchicine, which favors the aS form of the AC ring due to its alternative point chirality, is a substantially less potent tubulin inhibitor, the readily racemizable AC ring-bearing desacetamidocolchicine (2, DAAC, Figure ) exceptions, 12 biological studies on AC ring-containing analogs have relied on semisynthetic derivatives of the natural product source. Herein we describe a new and rapid synthetic strategy for AC ring synthesis featuring an oxidopyrylium cycloaddition/reductive ring-opening sequence. This new approach for the de novo construction of AC rings allowed for the synthesis of a series of molecules that are structural intermediates between DAAC and MTC, and are denoted