Polymer-supported chiral sulfonamide catalyzed one-pot reduction of β-keto nitriles: A practical synthesis of (R)-fluoxetine and (R)-duloxetine
Enantioselective reduction of β-keto nitriles to optically active 1,3-amino alcohols has been carried out in one step using an excess of borane-dimethyl sulfide complex as a reductant and a polymer-supported chiral sulfonamide as a catalyst with moderate to high enantioselectivity. The facile and enantioselective method to prepare optically active 1,3-amino alcohols to be converted into 3-aryloxy-3-arylpropylamine-type antidepressant drugs (R)-fluoxetine, and (R)-duloxetine is also reported.
Wang, Guangyin,Liu, Xingshun,Zhao, Gang
p. 1873 - 1879
(2007/10/03)
Chemoenzymatic synthesis2 of both enantiomers of fluoxetine, tomoxetine and nisoxetine: Lipase-catalyzed resolution of 3-aryl-3-hydroxypropanenitriles
A facile preparation of (±)-3-hydroxy-3-phenylpropanenitrile has been carried out by ring-opening of styrene oxide with NaCN in aqueous ethanol. Subsequent kinetic resolution of this material via lipase-mediated transesterification gave the S-alcohol and R-acetate in excellent yields and high enantioselectivities, particularly with lipase PS-C 'Amano' II. The effect of solvents and immobilization of the lipase has also been investigated. It is interesting to note that the use of immobilized lipase for this transesterification process in hydrophobic solvents (diisopropyl ether, toluene and hexane) enhanced the reaction rate drastically and gave optimal yields with high enantioselectivity (>99%). Moreover, enantiopure 3-hydroxy-3-phenylpropanenitrile products have been converted via enantioconvergent routes into the (R)- and (S)-enantiomers of the important anti-depressants fluoxetine, tomoxetine, nisoxetine and norfluoxetine.
Kamal, Ahmed,Khanna,Ramu
p. 2039 - 2051
(2007/10/03)
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