Streamlined Stereoselective Entry to (-)-Quinagolide and to 3-Substituted Octahydrobenzo[g]-Quinolines.

A very short stereoselective synthesis of enantiomerically pure (3S, 4aS, 10aR)-quinagolide has been developed. The key steps involved are a copper-catalyzed regioselective arylation of (S)-epichlorohydrin with 1,6-dimethoxynaphthalene and a diastereoselective trans-reduction of a cyclic enamine intermediate. The possibility to use both enantiomers of epichlorohydrin and the diastereodivergency found in the reduction process paves the way for a general preparation also in the nonracemic form of chiral trans-fused 3-substituted octahydrobenzo[g]quinolines that are privileged structures in medicinal chemistry.

[1]  Appasaheb L. Kadam,et al.  Formal Synthesis of (-)-Quinagolide: Diastereoselective Ring Expansion via a Bicyclic Aziridinium Ion Strategy to Access the Octahydrobenzo[g]quinoline Architecture. , 2021, The Journal of organic chemistry.

[2]  Appasaheb L. Kadam,et al.  Enantioselective Formal Total Synthesis of (-)-Quinagolide. , 2019, Organic letters.

[3]  A. Pontecorvi,et al.  Hyperprolactinemia: pathophysiology and therapeutic approach , 2015, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[4]  Jason M. Conley,et al.  Identification of a 2-phenyl-substituted octahydrobenzo[f]quinoline as a dopamine D₃ receptor-selective full agonist ligand. , 2012, Bioorganic & medicinal chemistry.

[5]  L. Vecchia,et al.  A New Practical Route for the Manufacture of (4aR,10aR)-9-Methoxy-1-methyl-6-trimethylsilanyl- 1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinoline , 2003 .

[6]  H. Katerinopoulos,et al.  N-(Iodopropenyl)-octahydrobenzo[f]- and -[g]quinolines: synthesis and adrenergic and dopaminergic activity studies. , 1998, Journal of medicinal chemistry.

[7]  H. Ohmizu,et al.  Simple Synthesis of trans-.ALPHA.,.BETA.-Dibenzyl-.GAMMA.-butyrolactone Lignans by Diastereoselective Reduction of .ALPHA.-Benzylidene-.BETA.-benzyl-.GAMMA.-butyrolactones Using NaBH4-NiCl2. , 1996 .

[8]  T. Ikariya,et al.  Asymmetric Transfer Hydrogenation of Imines , 1996 .

[9]  L. Overman,et al.  Regioselective opening of terminal epoxides with 2-(trialkylsilyl)allyl organometallic reagents , 1994 .

[10]  R. M. Hanson.  The synthetic methodology of nonracemic glycidol and related 2,3-epoxy alcohols , 1991 .

[11]  J. Schaus,et al.  SYNTHESIS OF THE DOPAMINE AGONIST (-)-QUINPIROLE , 1990 .

[12]  S. Torkelson,et al.  Synthesis and dopaminergic activity of 2-substituted octahydrobenzo[f]quinolines. , 1989, Journal of medicinal chemistry.

[13]  J. P. Long,et al.  p-Dimethoxy-substituted trans-octahydrobenzo[f]- and -[g]quinolines: synthesis and assessment of dopaminergic agonist effects. , 1986, Journal of medicinal chemistry.

[14]  T. Petcher,et al.  Octahydrobenzo[g]quinolines: potent dopamine agonists which show the relationship between ergolines and apomorphine. , 1985, Journal of medicinal chemistry.

[15]  Hyperprolactinemia , 2013, Journal of human reproductive sciences.