scholarly journals Development of dynamic kinetic resolution on large scale for (±)-1-phenylethylamine

2010 ◽  
Vol 6 ◽  
pp. 823-829 ◽  
Author(s):  
Lisa K Thalén ◽  
Jan-E Bäckvall
Keyword(s):  
Good Yield ◽  
Large Scale ◽  
Kinetic Resolution ◽  
Catalyst Loading ◽  
Acyl Donor ◽  
Dynamic Kinetic Resolution ◽  
Reaction Parameters ◽  
Ru Catalyst ◽  
Isopropyl Acetate ◽  
Acyl Donors

Candida antarctica lipase B (CALB) and racemization catalyst 4 were combined in the dynamic kinetic resolution (DKR) of (±)-1-phenylethylamine (1). Several reaction parameters have been investigated to modify the method for application on multigram scale. A comparison of isopropyl acetate and alkyl methoxyacetates as acyl donors was carried out. It was found that lower catalyst loadings could be used to obtain (R)-2-methoxy-N-(1-phenylethyl)acetamide (3) in good yield and high ee when alkyl methoxyacetates were used as acyl donors compared to when isopropyl acetate was used as the acyl donor. The catalyst loading could be decreased to 1.25 mol % Ru-catalyst 4 and 10 mg CALB per mmol 1 when alkyl methoxyacetates were used as the acyl donor.

Efficient Preparation of a Key Intermediate in the Synthesis of Roxifiban by Enzymatic Dynamic Kinetic Resolution on Large Scale¶

2004 ◽  
Vol 8 (1) ◽  
pp. 22-27 ◽  
Author(s):  
Jaan A. Pesti ◽  
Jinguao Yin ◽  
Lin-hua Zhang ◽  
Luigi Anzalone ◽  
Robert E. Waltermire ◽  
...  
Keyword(s):  
Large Scale ◽  
Kinetic Resolution ◽  
Dynamic Kinetic Resolution

Optimization of Chiral Resolution of (+/-)-1-Phenylethanol by Statistical Methods

2011 ◽  
Vol 9 (1) ◽  
Author(s):  
Ganapati D. Yadav ◽  
Jyoti B. Sontakke
Keyword(s):  
Kinetic Resolution ◽  
Batch Reactor ◽  
Immobilized Lipase ◽  
Enantiomeric Excess ◽  
Molar Ratio ◽  
Catalyst Loading ◽  
Acyl Donor ◽  
Reaction Conditions ◽  
Optimum Reaction ◽  
Synthetic Intermediate

Optically active 1-phenylethanol is used as a chiral building block and synthetic intermediate in pharmaceutical and fine-chemical industries. Lipase - catalyzed kinetic resolution of (R,S)-1-phenylethanol with vinyl acetate as an acyl donor and Candida antarctica immobilized lipase as a biocatalyst in a batch reactor was optimized using Response Surface Methodology (RSM). Four-factor-five-level central composite rotatable design (CCRD) was employed to evaluate the effect of synthesis parameters such as speed of agitation, enzyme loading, temperature and acyl donor/alcohol molar ratio, on conversion, enantiomeric excess (ee), enantioselectivity and initial rate. Optimum reaction conditions obtained were; mole ratio of acyl donor: ester of 2:1, temperature of 42.5 °C, catalyst loading of 1.6x10-3 g.cm-3 and speed of agitation of 336 rpm. Analysis of variance was performed to determine significantly affecting variables and interactions between the process parameters.

scholarly journals Biocatalytic synthesis of (S)-Practolol, a selective β-blocker

Biocatalysis ◽  
2016 ◽  
Vol 1 (1) ◽  
Author(s):  
Sachin Mulik ◽  
Saptarshi Ghosh ◽  
Jayeeta Bhaumik ◽  
Uttam C. Banerjee
Keyword(s):  
Adrenergic Receptor ◽  
Kinetic Resolution ◽  
Sol Gel ◽  
Enantiomeric Excess ◽  
Green Technology ◽  
Chemoenzymatic Synthesis ◽  
Acyl Donor ◽  
Pseudomonas Cepacia ◽  
Reaction Parameters ◽  
Β Blocker

AbstractThe present study describes an efficient chemoenzymatic synthesis of enantiopure (S)-Practolol, a selective β-adrenergic receptor blocker. Prior to the synthesis of the target, a synthetic protocol for (RS)-N-4-(3-chloro-2-hydroxypropoxy)phenylacetamide, an essential precursor, was developed. Various commercial lipases were screened for the kinetic resolution of (RS)- N-4-(3-chloro-2-hydroxypropoxy)phenylacetamide using toluene as solvent and vinyl acetate as an acyl donor. Among various lipases screened, Pseudomonas cepacia sol-gel AK showed the highest enantioselectivity (96% enantiomeric excess with 50% conversion), affording (S)-1-(4-acetamidophenoxy)-3-chloropropan-2-yl acetate. Optimization of the reaction parameters was carried out in order to find the best-suited conditions for the biocatalysis. Furthermore, the enantiopure intermediate was hydrolyzed and the resulting product was reacted with isopropylamine to afford (S)-Practolol. This biocatalytic procedure depicts a green technology for the synthesis of (S)-Practolol with better yield and enantiomeric excess.

Water content influences the selectivity of CALB-catalyzed kinetic resolution of phenoxymethyl-substituted secondary alcohols

2002 ◽  
Vol 80 (6) ◽  
pp. 577-581 ◽  
Author(s):  
Elisabeth Egholm Jacobsen ◽  
Thorleif Anthonsen
Keyword(s):  
Water Content ◽  
Water Activity ◽  
Kinetic Resolution ◽  
Relative Rate ◽  
High Water ◽  
High Water Content ◽  
Acyl Donor ◽  
Acyl Donors ◽  
Reaction Media ◽  
Derivatives Of

Derivatives of 1-phenoxy-2-alkanols were kinetically resolved by esterification with irreversible and reversible acyl donors using lipase B from Candida antarctica (Novozyme 435) as a catalyst. To optimize the relative rate of reaction (the E-value), esterifications in eight different solvents with different water activities were performed. For 3-bromo-1-phenoxy-2-propanol (1), the E-values in all the solvents were higher when the water activity was increased, while the E-values for 1-phenoxy-2-pentanol (2) and 3-chloro-1-phenoxy-2-propanol (3) decreased by increasing water activity. The water content of the various reaction media with the same water activity was determined. Solvents such as 1,4-dioxane, acetonitrile, and tetrahydrofuran contained much more water than hexane, carbon tetrachloride, cyclohexane, toluene, and benzene. At high-water activity, the high-water content of the former group of solvents resulted in termination of the reaction at low conversion. The reason seemed to be that the acyl donor and possibly also the produced esters were hydrolyzed. This was not the case when the esterification was performed in water-immiscible solvents with the same water activity.Key words: kinetic resolution, E-value, solvents, water activity, water content.

Dynamic kinetic resolution of secondary aromatic alcohols with new efficient acyl donors

2011 ◽  
Vol 22 (13) ◽  
pp. 1373-1378 ◽  
Author(s):  
Gang Xu ◽  
Yongjun Chen ◽  
Jianping Wu ◽  
Yongmei Cheng ◽  
Lirong Yang
Keyword(s):  
Kinetic Resolution ◽  
Dynamic Kinetic Resolution ◽  
Aromatic Alcohols ◽  
Acyl Donors
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