Transition-Metal-Mediated Chemo- and Stereoselective Total Synthesis of (−)-Galanthamine

Recent advances in the total synthesis of galantamine, a natural medicine for Alzheimer's disease

“…Trost and coworkers were the rst to break this paradigm and use a palladium catalyzed intramolecular Heck reaction. [69][70][71] Since then, numerous applications of transition metal catalyzed reactions, including all three Nobel Prize-winning reactions (the Heck coupling reaction, asymmetric hydrogenation reaction 22 and olen metathesis reaction 14,23,41 ), have been employed in the total synthesis of galantamine. 14,23,24,28,29 3.1 Heck reaction (Trost and Guillou)…”

Biotechnological Approaches to Optimize the Production of Amaryllidaceae Alkaloids

“…Consequently, it is often challenging and not always cost-effective nor ecological to chemically synthetize intact structures of AAs. Although there are some reports on successful chemical synthesis of AAs such as galanthamine, lycorine, or cherylline, the multiple steps involved lead to a low overall yield [ 18 , 19 , 20 , 21 , 22 , 23 , 24 ].…”

Biomimetic total synthesis of (−)-galanthamine via intramolecular anodic aryl–phenol coupling

“…5,7 Two recent examples achieved a final construction of the C ring after installing the ABD ring skeleton. 8 A recent report by Xu and co-workers uses a Rh-catalyzed C–C activation to form the tetracyclic carbon framework directly, 9 while Brown 10 and Zhao 11 have used other transition-metal mediated approaches. Although a variety of synthetic strategies have been reported so far, the commercial supplies of 1 are still using the Fröhlich–Jordis route 4 f in which the key phenolic oxidation coupling reaction proceeds in 40–54% yield by using 2 equivalents K 3 Fe(CN) 6 as the oxidant.…”

“…3 Numerous synthetic studies of (−)-galanthamine and its analogues have been performed and a number of total syntheses of 1 have been reported. [4][5][6][7][8][9][10][11] In the early stages of (−)-galanthamine syntheses, the biomimetic intramolecular oxidative coupling was the key step to build up the tetracyclic skeleton. 4 These methods typically require stoichiometric metal or hypervalent iodine reagents as oxidants and provide the products in only low to moderate yields.…”