Total Syntheses of Calyciphylline A-type Alkaloids (−)-10-deoxydaphnipaxianine A, (+)-daphlongamine E, and (+)-calyciphylline R via late-stage diallylic alcohol rearrangements

06 June 2022, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Consisting of more than 350 isolated members, the Daphniphyllum alkaloids possess complicated, polycyclic, and often caged skeletons along with diverse, interesting biological profiles. Among this natural product family, the representative calyciphylline A-type subfamily has triggered particular interest from the organic synthesis community. In this paper, we wish to report divergent total syntheses of three calyciphylline A-type alkaloids, namely (−)-10-deoxydaphnipaxianine A, (+)-daphlongamine E, and (+)-calyciphylline R. Our work highlights an efficient, divergent strategy via late-stage diallylic alcohol rearrangements, including an unprecedented oxidative Nazarov electrocyclization using an unfunctionalized diallylic alcohol and, an unusual, transannular allylic alcohol rearrangement. Other key transformations in our approach including an nitrile hydration using a highly efficient “donor-acceptor” platinum catalyst, an intramolecular Heck coupling and an intramolecular, regioselective pinacol coupling. Moreover, the power of selective amide reductions has also been showcased by novel and classic tactics. The strategies and methods used in our approach might provide further inspiration for natural product synthesis. Particularly, the novel oxidative Nazarov electrocyclization should be valuable in the chemical synthesis of other cyclopentenone-containing small molecules.


Total synthesis
Daphniphyllum alkaloids
Calyciphylline A-type Alkaloids
Nazarov cyclization
diallylic alcohol rearrangement
nitrile hydration
Selective amide reduction
Caged structure
Allylic oxidation

Supplementary materials

Supporting Information
Supplementary Information for Total Syntheses of Calyciphylline A-type Alkaloids (−)-10-deoxydaphnipaxianine A, (+)-daphlongamine E, and (+)-calyciphylline R via late-stage diallylic alcohol rearrangements


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