Total synthesis of (+)-galanthamine starting from d-glucose

The stereoselective total synthesis of (+)-galanthamine (+)-1 starting from d-glucose is described. The cyclohexene ring in (+)-1 was prepared in an optically active form from d-glucose using Ferrier's carbocyclization reaction, and the critical quaternary carbon was stereoselectively generated via chirality transfer based on the Claisen rearrangement of a cyclohexenol. The dibenzofuran skeleton was effectively constructed by the bromonium ion-mediated intramolecular cyclization of a cyclohexene possessing a phenolic ether function. After the introduction of a carbon-carbon double bond, the Pictet-Spengler type cyclization, followed by the reduction of the amide function completed the chiral synthesis of (+)-1.

Graphical abstractThe stereoselective total synthesis of (+)-galanthamine 1 starting from d-glucose is described. The quaternary carbon in 1 was stereoselectively generated via chirality transfer based on the Claisen rearrangement of a cyclohexenol, prepared from d-glucose using Ferrier's carbocyclization reaction. The dibenzofuran skeleton was constructed by the bromonium ion-mediated intramolecular cyclization.Download full-size image