Relative and Absolute Configuration of Allohedycaryol. Enantiospecific Total Synthesis of Its Enantiomer

The enantiomer of (+)-allohedycaryol, a germacrane alcohol isolated from giant fennel (Ferula communis L.), has been synthesized, thereby elucidating the relative and absolute stereochemistry of the natural product. The synthesis of (-)-allohedycaryol started from (+)-alpha-cyperone (5) which was available in relatively large quantities via alkylation of imine 7 derived from (+)-dihydrocarvone and (R)-(+)-1-phenylethylamine. In a number of steps 5 was converted into the mesylate 4with a regio- and stereoselective epoxidation as the key step. A Marshall fragmentation of 4 was used to prepare the trans,trans-cyclodeca-1,6-diene ring present in allohedycaryol. The conformation of synthetic (-)-allohedycaryol was elucidated via photochemical conversion into a bourbonane system. The synthesis of (-)-allohedycaryol also showed that natural (+)-allohedycaryol has the opposite absolute stereochemistry to that normally found in higher plants.