Synthesis and application of bimetallic chiral [Co(salen)]-type complexes: a new catalytic approach to synthesis of optically pure β-blockers via kinetic resolution of epichlorohydrin

2008 ◽  
Vol 22 (10) ◽  
pp. 583-591 ◽  
Author(s):  
Rahul B. Kawthekar ◽  
Wen-tao Bi ◽  
Geon-Joong Kim
Keyword(s):  
Kinetic Resolution ◽  
Β Blockers ◽  
Optically Pure

scholarly journals Lipase Catalyzed Synthesis of Enantiopure Precursors and Derivatives for β-Blockers Practolol, Pindolol and Carteolol

Catalysts ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 503
Author(s):  
Morten Gundersen ◽  
Guro Austli ◽  
Sigrid Løvland ◽  
Mari Hansen ◽  
Mari Rødseth ◽  
...  
Keyword(s):  
Building Block ◽  
Kinetic Resolution ◽  
Enantiomeric Excess ◽  
Catalytic Amount ◽  
Building Blocks ◽  
Β Blocker ◽  
Β Blockers ◽  
Optical Rotations ◽  
Reported Data ◽  
By Products

Sustainable methods for producing enantiopure drugs have been developed. Chlorohydrins as building blocks for several β-blockers have been synthesized in high enantiomeric purity by chemo-enzymatic methods. The yield of the chlorohydrins increased by the use of catalytic amount of base. The reason for this was found to be the reduced formation of the dimeric by-products compared to the use of higher concentration of the base. An overall reduction of reagents and reaction time was also obtained compared to our previously reported data of similar compounds. The enantiomers of the chlorohydrin building blocks were obtained by kinetic resolution of the racemate in transesterification reactions catalyzed by Candida antarctica Lipase B (CALB). Optical rotations confirmed the absolute configuration of the enantiopure drugs. The β-blocker (S)-practolol ((S)-N-(4-(2-hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide) was synthesized with 96% enantiomeric excess (ee) from the chlorohydrin (R)-N-(4-(3-chloro-2 hydroxypropoxy)phenyl)acetamide, which was produced in 97% ee and with 27% yield. Racemic building block 1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol for the β-blocker pindolol was produced in 53% yield and (R)-1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol was produced in 92% ee. The chlorohydrin 7-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one, a building block for a derivative of carteolol was produced in 77% yield. (R)-7-(3-Chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one was obtained in 96% ee. The S-enantiomer of this carteolol derivative was produced in 97% ee in 87% yield. Racemic building block 5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one, building block for the drug carteolol, was also produced in 53% yield, with 96% ee of the R-chlorohydrin (R)-5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one. (S)-Carteolol was produced in 96% ee with low yield, which easily can be improved.

scholarly journals ω-Amino Acid:Pyruvate Transaminase from Alcaligenes denitrificans Y2k-2: a New Catalyst for Kinetic Resolution of β-Amino Acids and Amines

2004 ◽  
Vol 70 (4) ◽  
pp. 2529-2534 ◽  
Author(s):  
Hyungdon Yun ◽  
Seongyop Lim ◽  
Byung-Kwan Cho ◽  
Byung-Gee Kim
Keyword(s):  
Amino Acids ◽  
Kinetic Resolution ◽  
Specific Activity ◽  
Expression System ◽  
Enantiomeric Excess ◽  
Selective Enrichment ◽  
Alcaligenes Denitrificans ◽  
Keto Acids ◽  
Optically Pure ◽  
High Stereoselectivity

ABSTRACT Alcaligenes denitrificans Y2k-2 was obtained by selective enrichment followed by screening from soil samples, which showed ω-amino acid:pyruvate transaminase activity, to kinetically resolve aliphatic β-amino acid, and the corresponding structural gene (aptA) was cloned. The gene was functionally expressed in Escherichia coli BL21 by using an isopropyl-β-d-thiogalactopyranoside (IPTG)-inducible pET expression system (9.6 U/mg), and the recombinant AptA was purified to show a specific activity of 77.2 U/mg for l-β-amino-n-butyric acid (l-β-ABA). The enzyme converts various β-amino acids and amines to the corresponding β-keto acids and ketones by using pyruvate as an amine acceptor. The apparent Km and V max for l-β-ABA were 56 mM and 500 U/mg, respectively, in the presence of 10 mM pyruvate. In the presence of 10 mM l-β-ABA, the apparent Km and V max for pyruvate were 11 mM and 370 U/mg, respectively. The enzyme exhibits high stereoselectivity (E > 80) in the kinetic resolution of 50 mM d,l-β-ABA, producing optically pure d-β-ABA (99% enantiomeric excess) with 53% conversion.

One-pot kinetic resolution–Mitsunobu reaction to access optically pure compounds, using silver salts in the substitution protocol

2020 ◽  
Vol 44 (48) ◽  
pp. 21238-21243
Author(s):  
Hiten B. Raval ◽  
Ashutosh V. Bedekar
Keyword(s):  
Kinetic Resolution ◽  
Mitsunobu Reaction ◽  
One Pot ◽  
Silver Salts ◽  
Pure Compounds ◽  
Optically Pure

Racemic carbinols were converted to chirally pure acetates by a combination of one-pot, enzyme mediated KR and Mitsunobu reaction with metal acetates. Use of AoNO3 or mixture with NaOAc gave excellent results. The protocol is further extended to introduce azide in place of acetate.

Esters of arylpropionic acids with 1,2:5,6-di-O-isopropylidene- and 1,2-O-isopropylidene-α-D-glucofuranose

1987 ◽  
Vol 52 (3) ◽  
pp. 766-774 ◽  
Author(s):  
Jiří Svoboda ◽  
Karel Čapek ◽  
Jaroslav Paleček
Keyword(s):  
Fractional Crystallization ◽  
Kinetic Resolution ◽  
Methyl Esters ◽  
Optically Pure ◽  
Derivatives Of

On fractional crystallization of 3-O-(2-(2-fluoro-4-biphenylyl)propionyl)-, 3-O-(2-(4-isobutylphenyl)propionyl)- and 3-O-(2-(6-methoxy-2-naphthyl)propionyl)-1,2 :5,6-di-O-isopropylidene-α-D-glucofuranoses V-VII optically pure R-diastereoisomers were isolated. The derivatives of 1,2-O-isopropylidene-α-D-glucofuranose obtained on partial deacetylation of esters V-VII were separated chromatographically to R and S-diastereoisomers. Their hydrolysis or transesterification afforded optically pure arylpropionic acids or their methyl esters, respectively. Kinetic resolution of the acids gives rise to esters V-VII enriched in R-diastereoisomer.

scholarly journals Conversion of racemic alcohols to optically pure amine precursors enabled by catalyst dynamic kinetic resolution: experiment and computation

2020 ◽  
Vol 56 (64) ◽  
pp. 9094-9097
Author(s):  
Luis Miguel Azofra ◽  
Mai Anh Tran ◽  
Viktoriia Zubar ◽  
Luigi Cavallo ◽  
Magnus Rueping ◽  
...  
Keyword(s):  
Asymmetric Synthesis ◽  
Base Metal ◽  
Kinetic Resolution ◽  
Dynamic Kinetic Resolution ◽  
Chiral Amine ◽  
Optically Pure

An unprecedented base metal catalysed asymmetric synthesis of α-chiral amine precursors from racemic alcohols is reported.

Overview: Enzyme-catalyzed Enantioselective Biotransformation of Chiral Active Compounds Used in Hypertension Treatment

2020 ◽  
Vol 24 (23) ◽  
pp. 2782-2791
Author(s):  
Joanna Chałupka ◽  
Adam Sikora ◽  
Aleksandra Kozicka ◽  
Michał Piotr Marszałł
Keyword(s):  
Kinetic Resolution ◽  
Enzymatic Reactions ◽  
Reaction Conditions ◽  
Enantiomerically Pure ◽  
Pharmaceutical Ingredients ◽  
Enzymatic Kinetic Resolution ◽  
Treatment Of Hypertension ◽  
Pure Compounds ◽  
Β Blockers ◽  
Asymmetric Carbon

Enzymatic kinetic resolution is one of the methods which allows for the synthesis of enantiomerically pure various active pharmaceutical ingredients. In contrast to chemical routes, enzymatic reactions have characteristics, including mild reaction conditions, a few byproducts, and relatively high activity of the used enzymes. β-adrenolytic drugs are widely used in the treatment of hypertension and cardiovascular disorders. Due to the fact that β- blockers possess an asymmetric carbon atom in their structure, they are presented in two enantiomeric forms. It was reported by many studies that only the (S)-enantiomers of these drugs possess the desired therapeutic effect, whereas the administration of the racemate may cause dangerous side effects, such as bronchoconstriction or diabetes. Nevertheless, β- blockers are still commercially available drugs mainly used in medicine as racemates, whereas there are several methods that are widely used in order to obtain enantiomerically pure compounds.

Application of the Bimodal Meso/Macroporous Composite Synthesized from MCM-41 Sol

2007 ◽  
Vol 7 (11) ◽  
pp. 3876-3879 ◽  
Author(s):  
Chang-Kyo Shin ◽  
Rahul B. Kawthekar ◽  
Geon-Joong Kim
Keyword(s):  
Mesoporous Silica ◽  
Kinetic Resolution ◽  
Three Dimensional ◽  
Porous Silica ◽  
Pore System ◽  
Silica Monoliths ◽  
Micrometer Size ◽  
Silica Wall ◽  
Optically Pure ◽  
Mcm 41

A route to synthesize porous materials with a bimodal macro/mesoscopic pore system has been investigated in this work. Polystyrene with sub-micrometer size was used as a template in the synthesis. The resulting mesoporous silica wall replicated inversely the morphology of polystyrene template and had highly ordered three-dimensional arrays of macro pores. Large and moldable meso/macro porous silica monoliths could be obtained in centimeter scale by using monodispersed polystyrene beads and MCM-41 sol solutions. These bimodal structured porous silicates have been used as supports for asymmetric kinetic resolution of racemic epoxides to synthesize optically pure epoxide.

Sign in / Sign up

Export Citation Format

Share Document