Total synthesis of (-)-galanthamine and (-)-lycoramine via catalytic asymmetric hydrogenation and intramolecular reductive Heck cyclization.

A synthetic strategy featuring efficient ruthenium-catalyzed asymmetric hydrogenation of racemic α-aryloxy cyclic ketone via dynamic kinetic resolution and palladium-catalyzed intramolecular reductive Heck cyclization has been developed for the asymmetric total synthesis of (-)-galanthamine (20.1%, 12 steps) and (-)-lycoramine (40.2%, 10 steps).

[1]  N. Chida,et al.  Total synthesis of (+)- and (-)-galanthamine , 2010 .

[2]  M. Beller,et al.  Zinc-catalyzed reduction of amides: unprecedented selectivity and functional group tolerance. , 2010, Journal of the American Chemical Society.

[3]  Qi‐Lin Zhou,et al.  Enantioselective Synthesis of Chiral β-Aryloxy Alcohols by Ruthenium-Catalyzed Ketone Hydrogenation via Dynamic Kinetic Resolution (DKR) , 2010 .

[4]  V. Lynch,et al.  Concise syntheses of (-)-galanthamine and (+/-)-codeine via intramolecular alkylation of a phenol derivative. , 2009, Journal of the American Chemical Society.

[5]  M. Oestreich.  The Mizoroki–Heck Reaction , 2009 .

[6]  N. Chida,et al.  Total synthesis of (+)-galanthamine starting from d-glucose , 2007 .

[7]  Tapas Paul,et al.  The enantioselective synthesis of (-)-lycoramine with the Birch-Cope sequence. , 2007, Journal of Organic Chemistry.

[8]  Y. Hamashima,et al.  Biomimetic synthesis of (+/-)-galanthamine and asymmetric synthesis of (-)-galanthamine using remote asymmetric induction. , 2006, Chemical & pharmaceutical bulletin.

[9]  Demosthenes Fokas,et al.  Enantioselective synthesis of (-)-dihydrocodeinone: a short formal synthesis of (-)-morphine. , 2006, The Journal of organic chemistry.

[10]  B. Trost,et al.  Divergent enantioselective synthesis of (-)-galanthamine and (-)-morphine. , 2005, Journal of the American Chemical Society.

[11]  Qi‐Lin Zhou,et al.  Ru(II)-SDP-complex-catalyzed asymmetric hydrogenation of ketones. Effect of the alkali metal cation in the reaction. , 2005, The Journal of organic chemistry.

[12]  Y. Hamashima,et al.  Total synthesis of (-)-galanthamine by remote asymmetric induction. , 2004, Angewandte Chemie.

[13]  B. Trost,et al.  Total syntheses of furaquinocin A, B, and E. , 2003, Journal of the American Chemical Society.

[14]  Qi‐Lin Zhou,et al.  Synthesis of spiro diphosphines and their application in asymmetric hydrogenation of ketones. , 2003, Journal of the American Chemical Society.

[15]  B. Trost,et al.  DYKAT of Baylis-Hillman adducts: concise total synthesis of furaquinocin E. , 2002, Journal of the American Chemical Society.

[16]  C. Guillou,et al.  An Efficient Total Synthesis of (±)-Galanthamine , 2001 .

[17]  B. Trost,et al.  Enantioselective Total Synthesis of (−)-Galanthamine , 2000 .

[18]  N. Cutler,et al.  Review of the acetylcholinesterase inhibitor galanthamine , 2000, Expert opinion on investigational drugs.

[19]  Gerhard Lauktien,et al.  Diastereo- and enantioselective synthesis of cis-2-hydroxycyclohexanamine and corresponding ethers by asymmetric reductive amination , 1997 .

[20]  Madeleine M. Joullié,et al.  Chemical and pharmacological characterization of galanthamine, an acetylcholinesterase inhibitor, and its derivatives. A potential application in Alzheimer's disease? , 1992 .

[21]  T. Saegusa,et al.  Synthesis of .alpha.,.beta.-unsaturated carbonyl compounds by palladium(II)-catalyzed dehydrosilylation of silyl enol ethers , 1978 .

[22]  J. Marco-Contelles,et al.  Synthesis and pharmacology of galantamine. , 2006, Chemical reviews.

[23]  K. A. Parker,et al.  A short stereospecific synthesis of (dl)-lycoramine. Control of relative stereochemistry by dipole effects , 1992 .

[24]  R. Larock,et al.  Synthesis of benzofurans via palladium-promoted cyclization of ortho-substituted aryl allyl ethers , 1988 .

[25]  K. Tomioka,et al.  A Biogenetic-type Asymmetric Synthesis of Optically Active Amaryllidaceae Alkaloids: (+)- and (-)-Galanthamine from L-Tyrosine , 1977 .

[26]  K. Tomioka,et al.  Approaches to the Biogenetic-type Asymmetric Synthesis of Some Amaryllidaceae Alkaloids , 1977 .

[27]  D. Barton,et al.  153. Phenol oxidation and biosynthesis. Part V. The synthesis of galanthamine , 1962 .