General Synthetic Approach to Diverse Taxane Cores

Chemical synthesis of natural products is typically inspired by the structure and function of a target molecule. When both factors are of interest, such as in the case of taxane diterpenoids, a synthesis can both serve as a platform for synthetic strategy development and enable new biological exploration. Guided by this paradigm, we present here a unified enantiospecific approach to diverse taxane cores from the feedstock monoterpenoid (S)-carvone. Key to the success of our approach was the use of a skeletal remodeling strategy which began with the divergent reorganization and convergent coupling of two carvonederived fragments, facilitated by Pd-catalyzed C-C bond cleavage tactics. This coupling was followed by additional restructuring using a Sm(II)-mediated rearrangement and a bioinspired, visible light induced, transannular [2 + 2] photocycloaddition. Overall, this divergent monoterpenoid remodeling/convergent fragment coupling approach to complex diterpenoid synthesis provides access to structurally disparate taxane cores which have set the stage for the preparation of a wide range of taxanes.

Automated summary

Chemical synthesis of natural products is often inspired by the structure and function of the target molecule, and this paper presents a unified enantiospecific approach to diverse taxane cores using (S)-carvone as the starting material, which involves skeletal remodeling and C-C bond cleavage strategies.