A Formal Total Synthesis of (2)-Cephalotaxine

thesis of cephalotaxine (1), the major alkaloid of the Cephalotaxus species, because of its unique structural features and antileukemic activity of its ester derivatives, harringtonine (2) and homoharringtonine (3). So far, eight total syntheses of (6)-1 including ours have been reported and the synthesis of (2)-1 has recently been achieved by Mori’s and Nagasaka’s groups. As a part of our own efforts to synthesize this alkaloid in an optically active form, we envisioned that the ketolactam 4, which had already been converted into (6)-cephalotaxine using three additional steps by Hanaoka and us, would be obtainable in an optically active form starting from D-proline as shown in the retrosynthetic format (Chart 1): one involves an intramolecular Heck reaction of the enone 5 and the other utilizes an intramolecular aldol condensation of the diketone 9 as a key step. Here we wish to report a formal total synthesis of (2)-1.