| 内容提要: |
Naturally occurring substances provided the cations to treat disease and continue to be a rich source and first mediinspiration for drug discovery and development. Among them are cytotoxic compounds, some of which are used to treat cancer. Shishijimicin A is a rare marine natural product endowed with extremely potent antitumor properties (IC50 = 0.48 pM against P388 leukemia cells). In view of its phenomenal biological activity and the new paradigm for targeted cancer chemotherapy, shishijimicin A constitutes a highly desirable payload for ADCs, an attractive possibility thus far hindered by its scarcity. In this presentation, I introduce the first total synthesis of shishijimicin A by K. C. Nicolaou group, rendering the molecule readily available for further biological investigations and opening the way for the construction of designed analogues of this valuable but rare molecule. |