Abstract
A concise, scalable, six-step (longest linear sequence) synthetic route to ovatodiolide scaffolds was developed for the first time. This protecting-group-free route features tandem ring-opening metathesis/ring-closing metathesis reactions to install the macrocycle-fused butenolide ring and a tandem allylboration/lactonization to build the α-methylene-γ-lactone. Our syntheses have enabled the determination of the hitherto unknown stereochemical configurations of this family of natural products. Preliminary tests of structure–activity relationships were conducted with four natural ovatodiolides and three analogues. Further assays indicated that the synthetic natural product isoovatodiolide can significantly decrease the population of hepatic cancer stem cells and reduce the tumorsphere-forming capability of HepG2 cells.
| Original language | English |
|---|---|
| Pages (from-to) | 10587-10590 |
| Number of pages | 4 |
| Journal | Angewandte Chemie - International Edition |
| Volume | 58 |
| Issue number | 31 |
| DOIs | |
| Publication status | Published - 29 Jul 2019 |
| Externally published | Yes |
Keywords
- antitumor agents
- configuration determination
- diterpenoids
- ovatodiolides
- total synthesis