Bioinspired Total Synthesis of Cephalotaxus Diterpenoids and Their Structural Analogues

Abstract Herein, we present a unified chemical synthesis of three subgroups of cephalotaxus diterpenoids. Key to the success lies in adopting a synthetic strategy that is inspired by biosynthesis but is opposite in nature. By employing selective one‐carbon introduction and ring expansion operations, we have successfully converted cephalotane‐type C 18 dinorditerpenoids (using cephanolide B as a starting material) into troponoid‐type C 19 norditerpenoids and intact cephalotane‐type C 20 diterpenoids. This synthetic approach has enabled us to synthesize cephinoid H, 13‐ oxo ‐cephinoid H, 7‐ oxo ‐cephinoid H, fortalpinoid C, 7‐ epi ‐fortalpinoid C, cephanolide E, and 13‐ epi ‐cephanolide E. Furthermore, through the development of an intermolecular asymmetric Michael reaction between β ‐oxo esters and β ‐substituted enones, we have achieved the enantioselective synthesis of advanced intermediates within our synthetic sequence, thus formally realizing the asymmetric total synthesis of the cephalotaxus diterpenoids family.