Total Synthesis of Yuzurine-type Alkaloid Daphgraciline

J Am Chem Soc. 2022 Oct 19;144(41):18823-18828. doi: 10.1021/jacs.2c09548. Epub 2022 Oct 5.

Abstract

The first total synthesis of daphgraciline has been achieved, which also represents the first example of the synthesis of Daphniphyllum yuzurine-type alkaloids (∼50 members). The unique bridged azabicyclo[4.3.1] ring system in the yuzurine-type subfamily was efficiently and diastereoselectively assembled via a mild type II [5+2] cycloaddition for the first time. The compact tetracyclic [6-7-5-5] skeleton was installed efficiently via an intramolecular Diels-Alder reaction, followed by a benzilic acid-type rearrangement. The synthetically challenging spiro tetrahydropyran moiety in the final product was installed diastereoselectively via a TiIII-mediated reductive epoxide coupling reaction. Potential access to enantioenriched daphgraciline is presented.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids*
  • Cycloaddition Reaction
  • Epoxy Compounds
  • Molecular Structure
  • Stereoisomerism

Substances

  • Alkaloids
  • Epoxy Compounds