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Updated: Jul 15, 2026
Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
Published on: April 27, 2017
Divergent enantioselective synthesis of (-)-galanthamine and (-)-morphine
Barry M Trost1, Weiping Tang, F Dean Toste
1Department of Chemistry, Stanford University, Stanford, California 94305, USA. bmtrost@stanford.edu
Abstract:
An efficient divergent synthetic strategy for the synthesis of the opiate and amaryllidaceae alkaloids emerges by employing a Pd-catalyzed asymmetric allylic alkylation (AAA) to set the stereochemistry. Three generations of syntheses of galanthamine are discussed in detail with particular focus on the scope of the palladium-catalyzed AAA reactions and intramolecular Heck reactions. The pivotal tricyclic intermediate is available in six steps from 2-bromovanillin and the monoester of methyl 6-hydroxycyclohexene-1-carboxylate. This intermediate requires only two steps to convert to (-)-galanthamine. Using a Heck vinylation, we found that the fourth ring of codeine/morphine could be formed. The final ring formation involves a novel visible light-promoted hydroamination. Thus, six steps are required to convert the pivotal tricyclic intermediate into codeine, which has been demethylated in high yield to morphine.
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