The First Enantioselective Total Synthesis of (-)-trans-Dihydronarciclasine

J Nat Prod. 2017 Jun 23;80(6):1909-1917. doi: 10.1021/acs.jnatprod.7b00208. Epub 2017 Jun 5.


A feasible and enantioselective total synthesis of (-)-trans-dihydronarciclasine [(-)-1], a highly biologically active alkaloid, was devised starting from vanillin (8). The key step of this new synthesis was an asymmetric, organocatalytic Michael addition, in which an optically active nitropentanone [(-)-13] was obtained from a butenone derivative (12). Excellent enantioselectivity (>99% ee) was achieved using the (8S,9S)-9-amino(9-deoxy)epiquinine (16) organocatalyst. The target molecule can be prepared in 13 steps from compound (-)-13. The total synthesis has provided a facile and first access to the ent-form of naturally occurring (+)-trans-dihydronarciclasine, a highly potent cytostatic alkaloid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemical synthesis*
  • Alkaloids / chemistry
  • Amaryllidaceae Alkaloids / chemical synthesis*
  • Amaryllidaceae Alkaloids / chemistry
  • Catalysis
  • Crystallography, X-Ray
  • Molecular Structure
  • Stereoisomerism


  • Alkaloids
  • Amaryllidaceae Alkaloids
  • dihydronarciclasine