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Organic Chemistry

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

Working Paper

Authors

  • Yan Zhang Department of Chemistry and Shenzhen Grubbs Institute and Guangdong Provincial Key Laboratory of Catalysis and Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Southern University of Science and Technology, Shenzhen 518055, China ,
  • Yuye Chen Department of Chemistry and Shenzhen Grubbs Institute and Guangdong Provincial Key Laboratory of Catalysis and Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Southern University of Science and Technology, Shenzhen 518055, China ,
  • Manrong Song Department of Chemistry and Shenzhen Grubbs Institute and Guangdong Provincial Key Laboratory of Catalysis and Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Southern University of Science and Technology, Shenzhen 518055, China ,
  • Bin Tan Department of Chemistry and Shenzhen Grubbs Institute and Guangdong Provincial Key Laboratory of Catalysis and Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Southern University of Science and Technology, Shenzhen 518055, China ,
  • Yujia Jiang Department of Chemistry and Shenzhen Grubbs Institute and Guangdong Provincial Key Laboratory of Catalysis and Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Southern University of Science and Technology, Shenzhen 518055, China ,
  • Chongyuan Yan Department of Chemistry and Shenzhen Grubbs Institute and Guangdong Provincial Key Laboratory of Catalysis and Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Southern University of Science and Technology, Shenzhen 518055, China ,
  • Yuyang Jiang Department of Chemistry and Shenzhen Grubbs Institute and Guangdong Provincial Key Laboratory of Catalysis and Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Southern University of Science and Technology, Shenzhen 518055, China ,
  • Xinyue Hu Department of Chemistry and Shenzhen Grubbs Institute and Guangdong Provincial Key Laboratory of Catalysis and Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Southern University of Science and Technology, Shenzhen 518055, China ,
  • Chengqian Zhang Department of Chemistry and Shenzhen Grubbs Institute and Guangdong Provincial Key Laboratory of Catalysis and Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Southern University of Science and Technology, Shenzhen 518055, China ,
  • Wenqing Chen Department of Chemistry and Shenzhen Grubbs Institute and Guangdong Provincial Key Laboratory of Catalysis and Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Southern University of Science and Technology, Shenzhen 518055, China ,
  • Jing Xu Department of Chemistry and Shenzhen Grubbs Institute and Guangdong Provincial Key Laboratory of Catalysis and Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Southern University of Science and Technology, Shenzhen 518055, China

Abstract

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.

Content

Supplementary material

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

Version History

Jun 06, 2022 Version 1

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License

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The content is available under CC BY NC 4.0 License CreativeCommons.org [opens in a new tab]

DOI

10.26434/chemrxiv-2022-6z22n
D O I: 10.26434/chemrxiv-2022-6z22n [opens in a new tab]

Funding

NSFC
21971104 and 22001114
Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis
ZDSYS20190902093215877
Guangdong Provincial Key Laboratory of Catalysis
No. 2020B121201002
Shenzhen Science and Technology Innovation Committee
JCYJ20170817110515599, KQTD20150717103157174
Guangdong Innovative Program
2019BT02Y335

Author’s competing interest statement

The author(s) have declared they have no conflict of interest with regard to this content

Ethics

The author(s) declare that they have sought and gained approval from the relevant ethics committee/IRB for this research and its publication.

Keywords

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

Publication

This content is an early or alternative research output and has not been peer-reviewed at the time of posting.