56105-81-8

Basic information

• Product Name: (2R)-2-(3-benzoylphenyl)propanoic acid
• Synonyms: (2R)-2-(3-benzoylphenyl)propanoic acid;(2R)-2-(3-Benzoylphenyl)propionic acid;(R)-2-(3-Benzoylphenyl)propionic acid;(R)-3-Benzoyl-a-methylphenylacetic acid;(R)-Ketoprophen;Benzeneacetic acid, 3-benzoyl-a-methyl-, (aR)- (9CI);Benzeneacetic acid, 3-benzoyl-a-methyl-, (R)-
• CAS NO: 56105-81-8
• Molecular Formula: C₁₆H₁₄O₃
• Molecular Weight: 254.2806
• Product Categories: Aromatics;Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 56105-81-8.mol
• Article Data: 38

Chemical Properties

• Melting Point: 77-78 °C
• Boiling Point: 431.316 °C at 760 mmHg
• Flash Point: 228.793 °C
• Appearance: /
• Density: 1.198g/cm³
• Vapor Pressure: 3.32E-08mmHg at 25°C
• Refractive Index: 1.591
• PKA: 4.23±0.10(Predicted)
• CAS DataBase Reference: (2R)-2-(3-benzoylphenyl)propanoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (2R)-2-(3-benzoylphenyl)propanoic acid(56105-81-8)
• EPA Substance Registry System: (2R)-2-(3-benzoylphenyl)propanoic acid(56105-81-8)

Safety Data

• Hazardous Substances Data: 56105-81-8(Hazardous Substances Data)

Usage

Uses

Anti-inflammatory; analgesic.

InChI:InChI=1/C16H14O3/c1-11(16(18)19)13-8-5-9-14(10-13)15(17)12-6-3-2-4-7-12/h2-11H,1H3,(H,18,19)/t11-/m1/s1

Synthetic route

C16H14O3*C17H21NO2 → R-ketoprofen (56105-81-8)

Conditions	Yield
With hydrogenchloride In water at 10 - 35℃;	98%

(RS)-ketoprofen vinyl ester (855519-35-6) → (S)-ketoprofen vinyl ester (911412-01-6) + R-ketoprofen (56105-81-8)

Conditions	Yield
With immobilized Lipozyme In 1,4-dioxane; water at 25℃; for 96h; Enzymatic reaction; optical yield given as %ee;	A 90% B n/a

(R)-2-(3-Benzoyl-phenyl)-propionic acid (R)-4,4-dimethyl-2-oxo-tetrahydro-furan-3-yl ester (156994-73-9) → R-ketoprofen (56105-81-8)

Conditions	Yield
With sodium carbonate In methanol; water for 2h; Ambient temperature;	85%

(3R)-1-phenyl-4,4-dimethyl-2-oxopyrrolidin-3-yl (αR)-2-(3-benzoylphenyl)propionate (1019853-52-1) → R-ketoprofen (56105-81-8)

Conditions	Yield
With hydrogenchloride; acetic acid In water at 120℃; for 2.5h; optical yield given as %ee;	63%

(+)-α-(3-benzylphenyl)propionic acid (22161-82-6) → S-ketoprofen (22161-81-5) + (3-acetylphenyl)(phenyl)methanone (66067-44-5) + R-ketoprofen (56105-81-8)

Conditions	Yield
With sodium hydroxide; potassium permanganate In water for 6h; Ambient temperature; Yield given;	A n/a B 28.4% C n/a

ketoprofen methyl ester (57872-48-7, 81601-91-4, 81601-93-6, 47087-07-0) → S-ketoprofen (22161-81-5) + R-ketoprofen (56105-81-8)

Conditions	Yield
With sodium hydroxide In water at 40℃; for 7.55h; titrisol buffer pH 8, carboxylesterase NP; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With tris hydrochloride; S. solfataricus esterase In water at 60℃; for 32h; pH=7.0; Enzymatic reaction;

ketoprofen (22071-15-4) → S-ketoprofen (22161-81-5) + R-ketoprofen (56105-81-8)

Conditions	Yield
With phosphate buffer; sodium dodecyl-sulfate; vancomycin at 20℃; Product distribution; electrophoretic enantioseparations, various substrates;
EtOH, TAPS/Tris buffer, pH 7.7;
lipase from Candida rugosa In 2,2,4-trimethylpentane; acetone Product distribution / selectivity; Resolution of racemate;

α-(3-benzoylphenyl)acrylic acid (74614-67-8) → S-ketoprofen (22161-81-5) + R-ketoprofen (56105-81-8)

Conditions	Yield
With (-)-Diop; chloro(1,5-hexadiene)rhodium(I) dimer; hydrogen; triethylamine; benzene In ethanol under 53200 Torr; for 20h; Ambient temperature; Yield given. Title compound not separated from byproducts;
With (-)-Diop; chloro(1,5-hexadiene)rhodium(I) dimer; hydrogen; triethylamine In ethanol; benzene under 11172 - 77140 Torr; Product distribution; different solvents, without NEt3, with KOH; other object: optical yield;

2-chloroethyl ester of 2-(3-benzoylphenyl)propionic acid (114315-58-1) → S-ketoprofen (22161-81-5) + R-ketoprofen (56105-81-8)

Conditions	Yield
With water at 40℃; for 40h; Candida rugosa lipase, pH 5; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With Candida rugosa lipase (Lipase OF); Tween-80 In water at 30℃; for 24h; pH=2.5; Title compound not separated from byproducts;

(R) ketoprofen glucuronide → D-glucuronic acid (6556-12-3, 489-91-8, 528-16-5, 552-12-5, 577-46-8, 643-33-4, 2240-07-5, 6294-16-2, 10133-02-5, 18402-78-3, 18968-14-4, 21179-08-8, 23018-83-9, 33599-45-0, 33599-46-1, 46171-67-9, 46171-69-1, 46172-26-3, 70021-34-0, 71031-08-8, 104195-06-4, 106499-29-0, 124817-72-7) + R-ketoprofen (56105-81-8)

Conditions	Yield
With human serum albumin In water at 37℃; pH=7.4; Enzyme kinetics; Further Variations:; Reagents; Hydrolysis; Enzymatic reaction; isotonic 0.067 M phosphate buffer;

ketoprofen chloride (59512-44-6, 71381-92-5, 109718-56-1) → S-ketoprofen (22161-81-5) + R-ketoprofen (56105-81-8)

Conditions	Yield
Stage #1: ketoprofen chloride With (S)-(3-OH-4,4-di-Me-2-oxopyrrolidin-1-yl)CH2COOH on resin; triethylamine In tetrahydrofuran at 0℃; Stage #2: With lithium hydroxide In tetrahydrofuran; water at 20℃; for 4h; Further stages. Title compound not separated from byproducts.;

(S)-2-(3-Benzoyl-phenyl)-propionic acid (S)-1-carbamoylmethyl-4,4-dimethyl-2-oxo-pyrrolidin-3-yl ester (362470-63-1) → S-ketoprofen (22161-81-5) + R-ketoprofen (56105-81-8) + (S)-(3-hydroxy-4,4-dimethyl-2-oxopyrrolidin-1-yl)acetamide

Conditions	Yield
With lithium hydroxide In tetrahydrofuran; water at 20℃; for 1h;

(R)-(-)-2-(3-benzoylphenyl)propionic acid ethyl ester (136656-96-7) → R-ketoprofen (56105-81-8)

Conditions	Yield
With novozyme 435 In water; acetonitrile at 45℃; for 45h;	360 mg

ketoprofen (22071-15-4) → R-ketoprofen (56105-81-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: Novozyme 435 / toluene / 2 h / 45 °C 2: 360 mg / Novozyme 435 / acetonitrile; H2O / 45 h / 45 °C View Scheme
Multi-step reaction with 3 steps 1.1: oxalyl chloride / 12 h / 40 °C 2.1: rink amide linker modified polystyrene grafted crowns; piperidine; benzotriazolyloxy-tris(dimethylamino)phosphonium(1+) PF6(1-) / diisopropylethylamine / dimethylformamide / 12 h / 20 °C 2.2: triethylamine / tetrahydrofuran / 12 h / 0 °C 2.3: 104 mg / trifluoroacetic acid / CH2Cl2 / 0.67 h 3.1: LiOH / tetrahydrofuran; H2O / 1 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: oxalyl chloride / 12 h / 40 °C 2.1: triethylamine; (S)-(3-OH-4,4-di-Me-2-oxopyrrolidin-1-yl)CH2COOH on resin / tetrahydrofuran / 0 °C 2.2: LiOH*H2O / tetrahydrofuran; H2O / 4 h / 20 °C View Scheme

ketoprofen chloride (59512-44-6, 71381-92-5, 109718-56-1) → R-ketoprofen (56105-81-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: rink amide linker modified polystyrene grafted crowns; piperidine; benzotriazolyloxy-tris(dimethylamino)phosphonium(1+) PF6(1-) / diisopropylethylamine / dimethylformamide / 12 h / 20 °C 1.2: triethylamine / tetrahydrofuran / 12 h / 0 °C 1.3: 104 mg / trifluoroacetic acid / CH2Cl2 / 0.67 h 2.1: LiOH / tetrahydrofuran; H2O / 1 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: 99.5 percent Spectr. / Et3N / toluene / -10 °C 2: 85 percent / Na2CO3 / methanol; H2O / 2 h / Ambient temperature View Scheme

ethyl α-(3-benzoylphenyl)acrylate (75116-78-8) → R-ketoprofen (56105-81-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 93 percent / 3percent KOH/H2O / tetrahydrofuran / 24 h / Ambient temperature 2: H2, 2/(-)-DIOP/NEt3 / ethanol; benzene / 11172 - 77140 Torr / different solvents, without NEt3, with KOH; other object: optical yield View Scheme

ketoprofen (22071-15-4) + bis(1-naphthyl)methanol (62784-66-1) → (R)-ketoprofen di(1-naphthyl)methyl ester (1116086-47-5) + (S)-ketoprofen di(1-naphthyl)methyl ester + S-ketoprofen (22161-81-5) + R-ketoprofen (56105-81-8)

Conditions	Yield
With (R)-(+)-2-phenyl-2,3-dihydrobenzo[d]imidazo[2,1-b]thiazole; p-Methoxybenzoic anhydride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 12h; Resolution of racemate; optical yield given as %ee;
With (-)-(S)-β-Np-BTM; 2,2-dimethylpropanoic anhydride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 12h; Inert atmosphere; Resolution of racemate; optical yield given as %ee; enantioselective reaction;
With benzoic acid anhydride; N-ethyl-N,N-diisopropylamine; (R)-(+)-2-phenyl-2,3-dihydrobenzo[d]imidazo[2,1-b]thiazole In dichloromethane at 20℃; for 6h; Product distribution / selectivity; Resolution of racemate;	A n/a B n/a C n/a D n/a

(R,S)-N-ketoprofenyl-1,2,4-triazole (1213788-21-6) → (S)-N-ketoprofenyl-1,2,4-triazole (1213788-33-0) + R-ketoprofen (56105-81-8)

Conditions	Yield
With Novozym 435; water In tert-butyl methyl ether at 45℃; Kinetics; Solvent; Concentration;

ketoprofen methyl ester (57872-48-7, 81601-91-4, 81601-93-6, 47087-07-0) → R-ketoprofen (56105-81-8) + methyl (2S)-2-(3-benzoylphenyl)propanoate + (R)-(-)-2-(3-benzoylphenyl)propionic acid methyl ester (81601-93-6)

Conditions	Yield
With Novozym 435; water In tert-butyl methyl ether at 45℃; Kinetics; Solvent; Concentration; optical yield given as %ee;

4-nitrophenyl 2-(3-benzoylphenyl)propanoate → C22H17NO5 + C22H17NO5 + S-ketoprofen (22161-81-5) + R-ketoprofen (56105-81-8)

Conditions	Yield
Stage #1: 4-nitrophenyl 2-(3-benzoylphenyl)propanoate With Pseudomonas aeruginosa lipase Met16Ala/Leu17Phe/Leu162Asn mutant In acetonitrile at 30℃; for 1.5h; pH=7.5; aq. phosphate buffer; Resolution of racemate; Enzymatic reaction; Stage #2: With hydrogenchloride In water; acetonitrile enantioselective reaction;

ketoprofen (22071-15-4) + 9,9‘-bis-phenanthrylmethanol (110282-71-8) → (R)-ketoprofen di(9-phenanthryl)methyl ester (1187670-14-9) + (S)-ketoprofen di(9-phenanthryl)methyl ester + S-ketoprofen (22161-81-5) + R-ketoprofen (56105-81-8)

Conditions	Yield
With p-Methoxybenzoic anhydride; N-ethyl-N,N-diisopropylamine; (R)-(+)-2-phenyl-2,3-dihydrobenzo[d]imidazo[2,1-b]thiazole In dichloromethane at 20℃; for 12h; Product distribution / selectivity; Resolution of racemate;	A n/a B n/a C n/a D n/a
With (R)-(+)-2-phenyl-2,3-dihydrobenzo[d]imidazo[2,1-b]thiazole; p-Methoxybenzoic anhydride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 12h; optical yield given as %ee; enantioselective reaction;

C19H15BrN2O2 (1268613-74-6) → C19H15BrN2O2 (1268614-30-7) + R-ketoprofen (56105-81-8)

Conditions	Yield
With Candida antarctica lipase B; water In tert-butyl methyl ether at 45℃; for 2h; Resolution of racemate; Enzymatic reaction; optical yield given as %ee; enantioselective reaction;

C26H22O4 → S-ketoprofen (22161-81-5) + R-ketoprofen (56105-81-8)

Conditions	Yield
With copper(l) chloride In methanol at 40℃; Inert atmosphere; optical yield given as %ee;

2-methyl-2-(3-benzoylphenyl)malonic acid (150360-24-0) → R-ketoprofen (56105-81-8)

Conditions	Yield
With Mesorhizobium sp. BNC1 arylmalonate decarboxylase Enzymatic reaction; enantioselective reaction;

ethyl 2-<3-benzoylphenyl>propionate (60658-04-0) → S-ketoprofen (22161-81-5) + R-ketoprofen (56105-81-8)

Conditions	Yield
With Thermotoga maritima esterase Tm1160 In aq. acetate buffer at 70℃; for 32h; pH=5.5; Enzymatic reaction; enantioselective reaction;	A n/a B n/a

ethyl 2-<3-benzoylphenyl>propionate (60658-04-0) → S-ketoprofen (22161-81-5) + R-ketoprofen (56105-81-8) + methyl (2S)-2-(3-benzoylphenyl)propanoate + (R)-(-)-2-(3-benzoylphenyl)propionic acid methyl ester (81601-93-6)

Conditions	Yield
With Yarrowia lipolytica Lip2p lipase In decane at 20℃; for 100h; Kinetics; Enzymatic reaction; enantioselective reaction;

ethyl 2-<3-benzoylphenyl>propionate (60658-04-0) → R-ketoprofen (56105-81-8) + methyl (2S)-2-(3-benzoylphenyl)propanoate

Conditions	Yield
With Candida rugose lipase CRL4 10X In decane at 20℃; for 100h; Kinetics; Enzymatic reaction; enantioselective reaction;

propan-1-ol (71-23-8) + R-ketoprofen (56105-81-8) → (R)-2-(3-Benzoyl-phenyl)-propionic acid propyl ester

Conditions	Yield
In 2,2,4-trimethylpentane at 30℃; lyophilized crude lipase (olive oil);	85%

R-ketoprofen (56105-81-8) + 1-amino-3-(dimethylamino)propane (109-55-7) → (R)-2-[(3-benzoyl)phenyl]-N-[3-(dimethylamino)propyl]propionamide

Conditions	Yield
Stage #1: R-ketoprofen With benzotriazol-1-ol; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 0.5h; Stage #2: 1-amino-3-(dimethylamino)propane In dichloromethane at 20℃;	75%

methanesulfonamide (3144-09-0) + R-ketoprofen (56105-81-8) → DF 1661

Conditions	Yield
Stage #1: R-ketoprofen With 1,1'-carbonyldiimidazole In dichloromethane at 0 - 5℃; for 2h; Stage #2: methanesulfonamide With 1,2-diazabicyclo[5.4.0]undec-7-ene In dichloromethane for 4h;	74%

epicholesterol (474-77-1) + R-ketoprofen (56105-81-8) → epi-cholesteryl (R)-2-(3-benzoylphenyl)propionate (913843-20-6)

Conditions	Yield
Stage #1: R-ketoprofen With dicyclohexyl-carbodiimide In dichloromethane at 0℃; for 0.5h; Stage #2: epicholesterol With dmap In dichloromethane at 0℃; for 8h;	74%

coenzyme A (85-61-0, 31416-98-5) + R-ketoprofen (56105-81-8) → C37H48N7O18P3S

Conditions	Yield
Stage #1: R-ketoprofen With 2,6-dimethylpyridine; chloroformic acid ethyl ester In dichloromethane at 20℃; for 1h; Stage #2: coenzyme A With sodium hydroxide In tetrahydrofuran; water at 20℃; for 2h; pH=6.2;

methanol (67-56-1) + R-ketoprofen (56105-81-8) → (R)-(-)-2-(3-benzoylphenyl)propionic acid methyl ester (81601-93-6)

Conditions	Yield
With sulfuric acid at 20℃;
With sulfuric acid at 80℃;

glycine ethyl ester hydrochloride (5680-79-5) + R-ketoprofen (56105-81-8) → [(R)-2-(3-Benzoyl-phenyl)-propionylamino]-acetic acid methyl ester

Conditions	Yield
Stage #1: R-ketoprofen With 1-hydroxybenzotriazol-hydrate; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 0 - 5℃; for 1h; Stage #2: glycine ethyl ester hydrochloride In N,N-dimethyl-formamide at 20℃;

R-ketoprofen (56105-81-8) → (R)-2-(3-Benzoyl-phenyl)-propionyl chloride

Conditions	Yield
With thionyl chloride for 3h; Heating;

cholesterol (57-88-5) + R-ketoprofen (56105-81-8) → epi-cholesteryl (R)-2-(3-benzoylphenyl)propionate (913843-20-6)

Conditions	Yield
Mitsunobu reaction;

R-ketoprofen (56105-81-8) → 3-ethylbenzophenone (66067-43-4)

Conditions	Yield
In phosphate buffer at 25℃; pH=7.4; Quantum yield; Kinetics; Further Variations:; Reagents; Photolysis;

R-ketoprofen (56105-81-8) → methyl (2R)-2-[3-(1-phenylethyl)phenyl]propanoate (875294-84-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: H2SO4 / 20 °C 2.1: n-BuLi / tetrahydrofuran; hexane / 3 h / 0 - 5 °C 2.2: 71 percent / tetrahydrofuran; hexane / 20 °C 3.1: H2 / Pd/C / ethanol / 18 h View Scheme

R-ketoprofen (56105-81-8) → (R),(R',S')-2-[3-(α-methylbenzyl)phenyl]propionyl chloride (454701-83-8)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: H2SO4 / 20 °C 2.1: n-BuLi / tetrahydrofuran; hexane / 3 h / 0 - 5 °C 2.2: 71 percent / tetrahydrofuran; hexane / 20 °C 3.1: H2 / Pd/C / ethanol / 18 h 4.1: 0.29 g / aq. KOH / dioxane / 20 °C 5.1: SOCl2 / 8 h / Heating View Scheme

R-ketoprofen (56105-81-8) → (2R)-2-[3-(1-phenylethyl)phenyl]propanoic acid (354904-38-4)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: H2SO4 / 20 °C 2.1: n-BuLi / tetrahydrofuran; hexane / 3 h / 0 - 5 °C 2.2: 71 percent / tetrahydrofuran; hexane / 20 °C 3.1: H2 / Pd/C / ethanol / 18 h 4.1: 0.29 g / aq. KOH / dioxane / 20 °C View Scheme

R-ketoprofen (56105-81-8) → methyl (2R)-2-[3-(1-phenylvinyl)phenyl]propanoate (859828-61-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: H2SO4 / 20 °C 2.1: n-BuLi / tetrahydrofuran; hexane / 3 h / 0 - 5 °C 2.2: 71 percent / tetrahydrofuran; hexane / 20 °C View Scheme

R-ketoprofen (56105-81-8) → N-{2-[3-(1-phenyl-ethyl)-phenyl]-propionyl}-methanesulfonamide

Conditions	Yield
Multi-step reaction with 5 steps 1.1: H2SO4 / 20 °C 2.1: n-BuLi / tetrahydrofuran; hexane / 3 h / 0 - 5 °C 2.2: 71 percent / tetrahydrofuran; hexane / 20 °C 3.1: H2 / Pd/C / ethanol / 18 h 4.1: 0.29 g / aq. KOH / dioxane / 20 °C 5.1: 1,1'-carbonyldiimidazole / CH2Cl2 / 2 h / 0 - 5 °C 5.2: 30 percent / diazabicyclo[5.4.0]undec-7-ene / CH2Cl2 / 4 h View Scheme

R-ketoprofen (56105-81-8) → [(R)-2-(3-Benzoyl-phenyl)-propionylamino]-acetic acid

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 1-hydroxybenzotriazole hydrate; 1,3-dicyclohexylcarbodiimide / dimethylformamide / 1 h / 0 - 5 °C 1.2: dimethylformamide / 20 °C 2.1: 0.31 g / aq. NaOH / dioxane / 20 °C View Scheme

Upstream product

• 57872-48-7 ketoprofen methyl ester 
• 22071-15-4 ketoprofen 
• 22161-82-6 (+)-α-(3-benzylphenyl)propionic acid 
• 74614-67-8 α-(3-benzoylphenyl)acrylic acid 
• 156994-73-9 (R)-2-(3-Benzoyl-phenyl)-propionic acid (R)-4,4-dimethyl-2-oxo-tetrahydro-furan-3-yl ester 
• 114315-58-1 2-chloroethyl ester of 2-(3-benzoylphenyl)propionic acid 
• 140148-26-1 (R) ketoprofen glucuronide 
• 59512-44-6 ketoprofen chloride 
• 362470-63-1 (S)-2-(3-Benzoyl-phenyl)-propionic acid (S)-1-carbamoylmethyl-4,4-dimethyl-2-oxo-pyrrolidin-3-yl ester 
• 136656-96-7 (R)-(-)-2-(3-benzoylphenyl)propionic acid ethyl ester 
• 75116-78-8 ethyl α-(3-benzoylphenyl)acrylate 
• 1019853-52-1 (3R)-1-phenyl-4,4-dimethyl-2-oxopyrrolidin-3-yl (αR)-2-(3-benzoylphenyl)propionate 
• 855519-35-6 (RS)-ketoprofen vinyl ester 
• 62784-66-1 bis(1-naphthyl)methanol 

Downstream Products

• 81601-93-6 (R)-(-)-2-(3-benzoylphenyl)propionic acid methyl ester 
• 913843-20-6 epi-cholesteryl (R)-2-(3-benzoylphenyl)propionate 
• 66067-43-4 3-ethylbenzophenone 
• 875294-84-1 methyl (2R)-2-[3-(1-phenylethyl)phenyl]propanoate 
• 454701-83-8 (R),(R',S')-2-[3-(α-methylbenzyl)phenyl]propionyl chloride 
• 354904-38-4 (2R)-2-[3-(1-phenylethyl)phenyl]propanoic acid 
• 859828-61-8 methyl (2R)-2-[3-(1-phenylvinyl)phenyl]propanoate 
• 160334-25-8 C₂₂H₁₉NO₂ 
• 430438-74-7 (R)-Ketoprofenoyl-CoA 
• 161527-65-7 (2R)-[3-(phenylcarbonyl)phenyl]propanenitrile 

Relevant articles and documents

Reshaping the active pocket of esterase Est816 for resolution of economically important racemates

Bacterial esterases are potential biocatalysts for the production of optically pure compounds. However, the substrate promiscuity and chiral selectivity of esterases usually have a negative correlation, which limits their commercial value. Herein, an efficient and versatile esterase (Est816) was identified as a promising catalyst for the hydrolysis of a wide range of economically important substrates with low enantioselectivity. We rationally designed several variants with up to 11-fold increased catalytic efficiency towards ethyl 2-arylpropionates, mostly retaining the initial substrate scope and enantioselectivity. These variants provided a dramatic increase in efficiency for biocatalytic applications. Based on the best variant Est816-M1, several variants with higher or inverted enantioselectivity were designed through careful analysis of the structural information and molecular docking. Two stereoselectively complementary mutants, Est816-M3 and Est816-M4, successfully overcame and even reversed the low enantioselectivity, and several 2-arylpropionic acid derivatives with highEvalues were obtained. Our results offer potential industrial biocatalysts for the preparation of structurally diverse chiral carboxylic acids and further lay the foundation for improving the catalytic efficiency and enantioselectivity of esterases.

Method for resolution of (+/-)-2-(3-benzoyl)-phenylpropionic acid

The invention provides a method for resolution of (+/-)-2-(3-benzoyl)-phenylpropionic acid. According to the method, (+/-)-2-(3-benzoyl)-phenylpropionic acid alkali salt serves as the raw material, (R)-3,4-dimethoxy-N-(1-phenethyl)-benzylamine hydrochloride serves as a resolving agent, and the raw material reacts with the resolving agent in the presence of solvent water to obtain diastereomeric salt of S-(+)-2-(3-benzoyl)-phenylpropionic acid and (R)-3,4-dimethoxy-N-(1-phenethyl)-benzylamine, namely resolving salt; then, the resolving salt is free with acid, and the S-(+)-2-(3-benzoyl)-phenylpropionic acid can be obtained. According to the method for resolution of the (+/-)-2-(3-benzoyl)-phenylpropionic acid, organic solvents do not need to be used in the forming process of the resolving salt, and water serves as a solvent. Besides, the consumption of the resolving agent is reduced by nearly 50%, and therefore the method is a resolving technology with more advantages.

Efficient resolution of profen ethyl ester racemates by engineered Yarrowia lipolytica Lip2p lipase

Enzyme-catalyzed enantiomer discrimination is still a great challenge for the development of industrial pharmaceutical processes. For the resolution of ibuprofen, naproxen and ketoprofen racemates, three major anti-inflammatory drugs, only lipases from Candida rugosa present a high selectivity if solvent and surfactant use is discarded. However, their catalytic activities are too low. In the present work, we demonstrate that the lipase Lip2p from the yeast Yarrowia lipolytica has a higher catalytic activity than C. rugosa lipases to hydrolyze the ethyl esters of ibuprofen, naproxen and ketoprofen, but its selectivity is not sufficient [E?=?52 (S); 11 (S) and 1.5 (R) respectively]. The enantioselectivity was further improved by site-directed mutagenesis, targeted at the substrate binding site and guided by molecular modelling studies. By investigating the binding modes of the (R)- and (S)-enantiomers in the active site, two amino acid residues located in the hydrophobic substrate binding site of the lipase, namely residues 232 and 235, were identified as crucial for enantiomer discrimination and enzyme activity. The (S) enantioselectivity of Lip2p towards ethyl ibuprofen esters was rendered infinite (E???300) by replacing V232 by an A or C residue. Substitution of V235 by C, M, S, or T amino acids led to a great increase in the (S)-enantioselectivity (E???300) towards naproxen ethyl ester. Finally, the variant V232F enabled the efficient kinetic resolution of ethyl ketoprofen ester enantiomers [(R)-enantiopreference; E???300]. In addition to the increase in selectivity, a remarkable increase in velocity by 2.6, 2.7 and 2.5?times, respectively, was found for ibuprofen, naproxen and ketoprofen ethyl esters.