Total synthesis of (+)- and (-)-galanthamine

The stereoselective total synthesis of (+)-galanthamine [(+)-1], an antipode of the natural product, and (-)-galanthamine [(-)-1] starting from D -glucose is described. The cyclohexene unit in (+)-1 was prepared in an optically active form from D -glucose using Ferrier's carbocyclization reaction, and the benzylic quaternary carbon was stereoselectively generated via chirality transfer by Johnson- or Eschenmoser-Claisen rearrangement. The dibenzofuran skeleton was effectively constructed by the bromonium ion-mediated intramolecular dealkylating etherification. After the introduction of a carbon-carbon double bond, the Pictet-Spengler type cyclization, followed by reduction of an amide function afforded (+)-1. Starting from D -glucose, (-)-galanthamine [(-)-1] was also totally synthesized.

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