- Method for synthesizing chiral secondary alcohol compound
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The invention discloses a method for synthesizing a chiral secondary alcohol compound. The method comprises the following step of: reacting a ketone compound in an aprotic organic solvent at room temperature and inert gas atmosphere under the action of a chiral cobalt catalyst and an activating agent by taking a combination of bis(pinacolato)diboron and alcohol or water as a reducing agent to obtain the chiral secondary alcohol compound. According to the method disclosed by the invention, a combination of pinacol diborate and alcohol or water which are cheap, stable and easy to obtain is taken as a reducing agent, and a ketone compound is efficiently reduced to synthesize a corresponding chiral secondary alcohol compound in an aprotic organic solvent under the action of a chiral cobalt catalyst; in a chiral cobalt catalyst adopted by the method, when a chiral ligand is PAOR, an activating agent is NaBHEt3 or NaOtBu and an adopted raw material is aromatic ketone, the yield is 80% or above, and the optical purity is 90% or above; and when the adopted raw material is alkane ketone, the yield can reach 70% or above, and the optical purity can reach 80% or above.
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Paragraph 0160-0172
(2021/05/29)
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- Asymmetric Hydrogenation of β-Aryloxy/Alkoxy Cinnamic Nitriles and Esters
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A highly efficient and enantioselective hydrogenation of β-aryloxy/alkoxy cinnamic nitriles and esters under mild conditions has been realized by using a rhodium catalyst with a chiral f-spiroPhos ligand. The method provides efficient access to the asymme
- Kong, Duanyang,Li, Meina,Wang, Rui,Zi, Guofu,Hou, Guohua
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supporting information
p. 4916 - 4919
(2016/10/18)
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- A method for preparing optically active 3-amino-1-phenylpropanol derivatives as an intermediate and a method for preparing optically active pharmaceutical products using the same
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The present invention relates to a method for preparing a 3-amino-1-phenylpropanol derivative having (R) or (S) optical activity with 80% or more of an enantiomeric excess (ee), which includes a step of performing an asymmetric reduction reaction in the presence of a spiroborate ester catalyst and a hydrogen donor. The invention also relates to a method for preparing an optically active pharmaceutical product, which includes a step of preparing a (R)- or (S)-3-amino-1-phenylpropanol derivative, that is an intermediate, by using the catalyst.(AA) 3-amino-1-phenylpropanol(BB) Tomoxetine(CC) Nisoxetine(DD) FluoxetineCOPYRIGHT KIPO 2016
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Paragraph 0207; 0208; 0212; 0213
(2016/11/09)
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- Molecular basis for selective serotonin reuptake inhibition by the antidepressant agent fluoxetine (Prozac)
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Inhibitors of the serotonin transporter (SERT) are widely used antidepressant agents, but the structural mechanism for inhibitory activity and selectivity over the closely related norepinephrine transporter (NET) is not well understood. Here we use a combination of chemical, biological, and computational methods to decipher the molecular basis for high-affinity recognition in SERT and selectivity over NET for the prototypical antidepressant drug fluoxetine (Prozac; Eli Lilly, Indianapolis, IN). We show that fluoxetine binds within the central substrate site of human SERT, in agreement with recent X-ray crystal structures of LeuBAT, an engineered monoamine-like version of the bacterial amino acid transporter LeuT. However, the binding orientation of fluoxetine is reversed in our experimentally supported model comparedwith the LeuBAT structures, emphasizing the need for careful experimental verification when extrapolating findings from crystal structures of bacterial transporters to human relatives. We find that the selectivity of fluoxetine and nisoxetine, a NET selective structural congener of fluoxetine, is controlled by residues in different regions of the transporters, indicating a complex mechanism for selective recognition of structurally similar compounds in SERT and NET. Our findings add important new information on the molecular basis for SERT/NET selectivity of antidepressants, and provide the first assessment of the potential of LeuBAT as a model system for antidepressant binding in human transporters, which is essential for future structure-based drug development of antidepressant drugs with fine-tuned transporter selectivity. Copyright
- Andersen, Jacob,Stuhr-Hansen, Nicolai,Zachariassen, Linda Gronborg,Koldso, Heidi,Schiott, Birgit,Stromgaard, Kristian,Kristensen, Anders S.
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p. 703 - 714
(2014/04/17)
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- Chemoenzymatic asymmetric synthesis of fluoxetine, atomoxetine, nisoxetine, and duloxetine
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The asymmetric synthesis of two well-known anti-depressant drugs, fluoxetine and duloxetine has been accomplished in a chemoenzymatic manner. The main highlight of the synthesis is the enantioselective cyanohydrin formation by a plant (R)-HNL (hydroxynitrile lyase). The enantiopure cyanohydrins are then synthetically manipulated into the above two drug molecules and two of their structural analogues, atomoxetine and nisoxetine.
- Rej, Rohan Kalyan,Das, Tapas,Hazra, Suman,Nanda, Samik
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p. 913 - 918
(2013/09/23)
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- Synthesis and C-11 labeling of three potent norepinephrine transporter selective ligands ((R)-nisoxetine, lortalamine, and oxaprotiline) for comparative PET studies in baboons
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Three potent antidepressants, (R)-nisoxetine, lortalamine, and oxaprotiline, with high affinity and high selectivity for the norepinephrine transporter (NET) were synthesized and radiolabeled with C-11 via [ 11C]methylation. The reference compo
- Lin, Kuo-Shyan,Ding, Yu-Shin
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p. 4658 - 4666
(2007/10/03)
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- Chemoenzymatic synthesis2 of both enantiomers of fluoxetine, tomoxetine and nisoxetine: Lipase-catalyzed resolution of 3-aryl-3-hydroxypropanenitriles
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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
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p. 2039 - 2051
(2007/10/03)
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- Chemoenzymatic synthesis of the non-tricyclic antidepressants Fluoxetine, Tomoxetine and Nisoxetine
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3-Chloro-1-phenylpropan-1-ol and the corresponding butanoate, 3-chloro-1-phenyl-1-propyl butanoate, were kinetically resolved using lipase B from Candida antarctica catalysis by transesterification and hydrolysis respectively. The resulting chiral building blocks (S)- and (R)-3-chloro-1-phenylpropanol were converted into both enantiomers of the antidepressant drugs, Fluoxetine, Tomoxetine and Nisoxetine. The Royal Society of Chemistry 2000.
- Liu, Hui-Ling,Hoff, Bard Helge,Anthonsen, Thorleif
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p. 1767 - 1769
(2007/10/03)
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- An efficient route to enantiomerically pure antidepressants: Tomoxetine, nisoxetine and fluoxetine
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Both enantiomers (R)- and (S)-3-chloro-1-phenyl-1-propanol can be obtained conveniently by an efficient enzymatic resolution process. They can be converted via enantioconvergent routes into all enantiomers of the important antidepressants (R)- and (S)-Tomoxetine, Fluoxetine and Nisoxetine.
- Schneider,Goergens
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p. 525 - 528
(2007/10/02)
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- Treatment of obesity with aryloxyphenylpropylamines
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3-Aryloxy-3-phenylpropylamines and acid addition salts thereof are useful in blocking uptake of monoamines by brain neurons, and are thus effective in treating disorders of sleep, sexual performance, appetite, muscular function, and pituitary function.
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- Aryloxyphenylpropylamines in treating depression
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3-Aryloxy-3-phenylpropylamines and acid additions salts thereof, useful as psychotropic agents, particularly as anti-depressants.
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