Abstract: Natural products with a high ratio of sp3-hybridized atoms and oxygen-substituted stereogenic centers represent privileged structures for the development of pharmaceuticals and chemical probes.  The multiple oxygen functionalities of these natural products endow their potent and selective biological activities, although they significantly heighten the challenge of their chemical assemblies.1  We focused on developing efficient strategies for the total syntheses of this biologically and chemically important class of molecules.  Specifically, we have designed and devised radical-based strategies for assembling highly oxygenated natural products.2,3  In this lecture, we report the development of the radical coupling reactions and the synthetic routes to resiniferatoxin (1),4,5 puberuline (2),6 and euonymine (3)7 by applying the radical chemistry.   

References

1.   Urabe, D.; Asaba, T.; Inoue, M. Chem. Rev. 2015, 115, 9207.

2.   Inoue, M. Acc. Chem. Res. 2017, 50, 460.

3.   Nagatomo, M.; Inoue, M. Acc. Chem. Res. 2021, 54, 595.

4.   Hirose, A.; Watanabe, A.; Ogino, K.; Nagatomo, M.; Inoue, M. J. Am. Chem. Soc. 2021, 143, 12387.

5.   Hikone, Y.; Kato, T.; Nagatomo, M.; Inoue, M. Org. Lett. 2022, 24, 929.

6.   Shimakawa, T.; Nakamura, S.; Asai, H.; Hagiwara, K.; Inoue, M. J. Am. Chem. Soc. 2023, 145, 600.

7.   Wang, Y.; Nagai, T.; Watanabe, I.; Hagiwara, K.; Inoue, M. J. Am. Chem. Soc. 2021, 143, 21037.