Total Synthesis of (±)-Cephalotaxine-Type Alkaloids via a Semipinacol Rearrangement/Intramolecular Schmidt Sequence

Cephalotaxus alkaloids represent a family of structurally unique and biologically important natural products, many of which exhibit potent antileukemic and antitumor activities. In this work, we report an efficient synthetic strategy that combines semipinacol rearrangement with a subsequent intramolecular Schmidt reaction for the rapid assembly of the characteristic azaquaternary tetracyclic skeleton common to Cephalotaxus alkaloids. Starting from this versatile common intermediate, we accomplished the total synthesis of (±)-demethylcephalotaxinone and achieved the formal synthesis of several representative Cephalotaxus alkaloids, including (±)-cephalotaxine. This approach provides a new strategy for the synthesis of Cephalotaxus alkaloids, which will facilitate the preparation of synthetic analogs for further biological and medicinal studies.