482374-40-3Relevant articles and documents
Divergent enantioselective synthesis of (-)-galanthamine and (-)-morphine
Trost, Barry M.,Tang, Weiping,Toste, F. Dean
, p. 14785 - 14803 (2007/10/03)
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.
An efficient enantioselective synthesis of (-)-galanthamine
Trost, Barry M.,Tang, Weiping
, p. 2795 - 2797 (2007/10/03)
An effective sequence: Palladium-catalyzed asymmetric allylic alkylation, Heck cyclization, and diastereoselective allylic oxidation were used in the total synthesis of (-)-galanthamine (3) in 14.8 % overall yield (from 1 and 2, Troc = 2,2,2-trichloroethoxycarbonyl) and with 96 % ee. This improved procedure provides the shortest and most efficient nonbiomimetic synthesis of the acetylcholinesterase inhibitor.
