Application of the photocyclization reaction of 1,2-cyclopenta-fused pyridinium perchlorate to formal total syntheses of (−)-cephalotaxine

Abstract Two strategies for the formal total synthesis of (−)-cephalotaxine, based on pyridinium salt photochemistry, are described. The routes begin with photocyclization reaction of 1,2-cyclopenta-fused pyridinium perchlorate. This process efficiently and regioselectively produces a tricyclic aziridine, which undergoes sequential aziridine ring opening and enzymatic desymmetrization to generate enantio-enriched intermediates that contain the spirocyclic D,E-ring system found in cephalotaxine. These substances serve as precursors to late stage key intermediates used by Mori, Tietze, and Yoshida in earlier syntheses of (−)-cephalotaxine.