Organic Chemistry

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

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

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Supplementary material

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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