ent-Kaurane-based regio- and stereoselective inverse electron demand hetero-Diels-Alder reactions: synthesis of dihydropyran-fused diterpenoids

Org Biomol Chem. 2014 Nov 14;12(42):8442-52. doi: 10.1039/c4ob01040j.


A mild and concise approach for the construction of a 3,4-dihydro-2H-pyran ring integrated into the A-ring of the natural product oridonin using an optimized inverse electron demand hetero-Diels-Alder (IED HDA) reaction is reported herein. A self-dimerization of the exocyclic enone installed in the A-ring through a homo-HDA reaction was identified to exclusively give a dimeric ent-kaurane diterpenoid with the spirochroman core. Moreover, efficient cross-HDA cycloadditions of this enone with various vinyl ethers or vinyl sulfides, instead of its own homo-HDA dimerization, were achieved in a regio- and stereoselective manner, thus providing access to novel dihydropyran-fused diterpenoids as potential anticancer agents to overcome chemoresistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Products / chemical synthesis*
  • Biological Products / chemistry
  • Crystallography, X-Ray
  • Cycloaddition Reaction
  • Dimerization
  • Diterpenes, Kaurane / chemical synthesis*
  • Diterpenes, Kaurane / chemistry
  • Models, Molecular
  • Pyrans / chemical synthesis*
  • Pyrans / chemistry
  • Stereoisomerism


  • Biological Products
  • Diterpenes, Kaurane
  • Pyrans
  • oridonin