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

• Published in: Tetrahedron letters Vol. 48; no. 36; pp. 6267 - 6270
• Main Authors: Tanimoto, Hiroki, Kato, Tomoaki, Chida, Noritaka
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 03.09.2007; Elsevier
• Subjects: Chemistry; Chemistry, Organic; Chiral synthesis; Claisen rearrangement; Galanthamine; Physical Sciences; Science & Technology; Galanthamine; Chiral synthesis; Claisen rearrangement; galanthamine; AMARYLLIDACEAE ALKALOIDS; ORGANIC-SYNTHESIS; (-)-GALANTHAMINE; ALZHEIMERS-DISEASE; chiral synthesis; EFFICIENT SYNTHESIS; (+/-)-GALANTHAMINE; REMOTE ASYMMETRIC INDUCTION; L-TYROSINE
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2007.07.042

The 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. 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.