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Slideshow

The Total Synthesis of Daphniphyllum Alkaloids

Jarvis Hill
Jarvis Hill
Graduate Student, Department of Chemistry
University of Georgia
ONLINE ONLY
Organic Seminar

Daphniphyllum alkaloids have a rich history dating back to the isolation of Daphniphyllum macropodum Miquel in 1909 by Yagi.1 Pioneering work in the 1960s by Hirata and colleagues resulted in the isolation of daphniphylline and yuzurimine alkaloids, and subsequently, a total of over 330 Daphniphyllum alkaloids have been reported from the Daphniphyllum genus.2-5 In view of their intriguing biological activities including anti-cancer and  anti-HIV activity, coupled with their complex azapolycyclic structures, various synthetic groups have been engaged in the syntheses of Daphniphyllum alkaloids culminating in over  30 impressive total syntheses.4-5 This seminar will present a historical perspective on the synthesis of Daphniphyllum alkaloids, beginning with the pioneering studies performed by Heathcock6-8 utilizing biomimetic tactics.  A series of recent total syntheses of Daphniphyllum alkaloids spanning the period from 2019-2021 reported by the Sarpong9, Xu10, Li11, and Qiu12 groups will then be presented which feature state-of-the-art synthetic methods towards these complex azapolycyclic natural products.

Daphniphyllum Alakloids

References:

1) Yagi, S. Daphniphyllum Alkaloid. Kyoto Igaku Zasshi 1909, 6, 208-222.

2) Irikawa, H.; Sakurai, H.; Sakabe, N.; Hirata, Y. Isolation of Two New Alkaloids from Daphniphyllum macropodum Miguel. Tetrahedron Lett. 1966, 7, 5363-5368.

3) Sakabe, N.; Irikawa, H.; Sakurai, H.; Hirata, Y. Isolation of Three New Alakloids from Daphniphyllum macropodum Miguel. Tetrahedron Lett. 1966, 7, 963-964.

4) Chattopadhyaya, A. K.; Henessian, S. Recent Progress in the Chemistry of Daphniphyllum Alakloids. Chem. Rev. 2017, 117, 4104-4146.

5) Guo, L.-D.; Chen, Y.; Xu, J. Total Synthesis of Daphniphyllum Alkaloids: From Bicycles to Diversified Caged Structures. Acc. Chem. Res. 2020, 53, 2726-2737.

6) Heathcock, C. H.; Davidsen, S. K.; Mills, S.; Sanner, M. A. Total Synthesis of (+)-methyl homodaphniphyllate. J. Am. Chem. Soc. 1986, 108, 5650-5651.

7) Ruggeri, R.; Hansen, M. M.; Heathcock, C. H. Total Synthesis of (±)-methyl homosecodaphniphyllate. A Remarkable New Tetracyclization Reaction. J. Am. Chem. Soc. 1988, 110¸8734-8736.

8) Piettre, S.; Heathcock, C. H. Biomimetic Total Synthesis of proto-daphniphylline. Science 1990, 248, 1532-1534.

9) Hugelshofer, C. L.; Palani, V.; Sarpong, R. Calyciphylline B-Type Alkaloids: Total Synthesis of (-)-Daphlongamine H and (-)-Isodaphlongamine H. J. Am. Chem. Soc. 2019, 141, 8431-8435.

10) Guo, L.-D.; Hu, J.; Zhang, Y.; Tu, W.; Zhang, Y.; Pu, F.; Xu, J. Enantioselective Total Synthesis of (-)-Caldaphnidine O via a Radical Cyclization Cascade. J. Am. Chem. Soc. 2019, 141, 13043-13048.

11) Xu, G.; Wu, J.; Li, L.; Lu, Y.; Li, C. Total Synthesis of (-)-Daphnezomines A and B. J. Am. Chem. Soc. 2020, 142, 15240-15245.

12) Wang, B.; Xu, B.; Xun, W.; Guo, Y.; Zhang, J.; Qiu, F. G. A General Strategy for the Construction of Calyciphylline A-Type Alkaloids: Divergent Total Syntheses of (-)-Daphenylline and (-)-Himalensine A. Angew. Chem. Int. Ed. 2021 DOI: 10.1002/anie.202016212.

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