949-99-5

Basic information

• Product Name: 4-Nitro-3-phenyl-L-alanine
• Synonyms: P-NITRO-PHENYLALANINE;P-NITRO-L-PHENYLALANINE;P-NITRO-2-PHENYLALANINE;(P-NO2)PHE-OH;(S)-4-NITROPHENYLALANINE;(S)-4-NITROPHENYLALANINE HYDRATE;(S)-2-AMINO-3-(4-NITROPHENYL)PROPANOIC ACID;RARECHEM BK PT 0073
• CAS NO: 949-99-5
• Molecular Formula: C₉H₁₀N₂O₄
• Molecular Weight: 210.19
• EINECS: 213-446-8
• Product Categories: Amino Acids;Phenylalanine analogs and other aromatic alpha amino acids;Amino ACIDS SERIES;chiral;Phenylalanine [Phe, F]
• Mol File: 949-99-5.mol
• Article Data: 59

Chemical Properties

• Melting Point: 236-239°C (dec.)
• Boiling Point: 414.1 °C at 760 mmHg
• Flash Point: 204.2 °C
• Appearance: white to light yellow crystal powder
• Density: 1.408 g/cm³
• Vapor Pressure: 1.34E-07mmHg at 25°C
• Refractive Index: 1.614
• Storage Temp.: Store at RT.
• PKA: 2.12±0.10(Predicted)
• CAS DataBase Reference: 4-Nitro-3-phenyl-L-alanine(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Nitro-3-phenyl-L-alanine(949-99-5)
• EPA Substance Registry System: 4-Nitro-3-phenyl-L-alanine(949-99-5)

Safety Data

• Hazard Codes: Xn,C,F
• Statements: 36/37/38-22-34-11
• Safety Statements: 26-36/37/39-22-45-16
• RIDADR: 2811
• RTECS: AY7400000
• Hazardous Substances Data: 949-99-5(Hazardous Substances Data)

Usage

Chemical Properties

white to light yellow crystal powde

Uses

4-Nitro-L-phenylalanine is used in the studies on the rational manipulation of protein structures for the expansion of the genetic code with non natural amino acids into protein via in vitro translation.

InChI:InChI=1/C9H10N2O4/c10-8(9(12)13)5-6-1-3-7(4-2-6)11(14)15/h1-4,8H,5,10H2,(H,12,13)

Synthetic route

L-phenylalanine (63-91-2) → 4-nitro-3-phenyl-L-alanine (949-99-5)

Conditions	Yield
Stage #1: L-phenylalanine With sulfuric acid; nitric acid at 20℃; for 5h; Stage #2: With sodium hydroxide pH=2 - 3;	95.2%
Stage #1: L-phenylalanine With sulfuric acid; nitric acid In water at 20℃; Stage #2: With sodium hydroxide In water pH=2 - 3;	95.2%
Stage #1: L-phenylalanine With sulfuric acid; nitric acid at 10℃; for 2.5h; Stage #2: With ammonia In water pH=5 - 6;	94%

N-acetyl-4-nitro-L-phenylalanine (17363-92-7) → 4-nitro-3-phenyl-L-alanine (949-99-5)

Conditions	Yield
With Acylase I enzyme from porcine kidney; water at 24.9℃; Rate constant;	83%
With hydrogenchloride

p-nitrocinnamic acid (619-89-6) → 4-nitro-3-phenyl-L-alanine (949-99-5)

Conditions	Yield
With ammonium hydroxide; borane-ammonia complex In aq. buffer at 37℃; pH=9.6; Enzymatic reaction;	57%
With ammonium bisulphate; EncP-R299K variant at 55℃; for 22h; pH=8.3; Enzymatic reaction; stereoselective reaction;	n/a

4-nitrophenylalanine (1991-83-9, 2922-40-9, 56613-61-7, 949-99-5) → 4-nitro-3-phenyl-L-alanine (949-99-5)

Conditions	Yield
With sodium hydroxide; oxygen at 30℃; for 42h; pH=7.3; aq. buffer; Enzymatic reaction; optical yield given as %ee; enantioselective reaction;	51%

p-nitrocinnamic acid (619-89-6) → (R)-3-amino-3-(4'-nitrophenyl)propanoic acid (501120-99-6) + 4-nitro-3-phenyl-L-alanine (949-99-5)

Conditions	Yield
With ammonia at 25℃; pH=9; Kinetics; aq. buffer; Enzymatic reaction; regioselective reaction;	A 8% B n/a

N-benzoyl-(4'-nitro)phenylalanine (101468-97-7) → 4-nitro-3-phenyl-L-alanine (949-99-5)

Conditions	Yield
With acylase-substance from pseudomonas

(L)-p-Nitrophenylalanine methyl ester (81677-60-3) → 4-nitro-3-phenyl-L-alanine (949-99-5)

Conditions	Yield
With water; chymotrypsin at 25℃; Rate constant;

N-acetyl-4-nitro-DL-phenylalanine (62561-97-1) → 4-nitro-3-phenyl-L-alanine (949-99-5)

Conditions	Yield
With phosphate buffer; acylase I from porcine kidney at 24.9℃; for 2h;

glycine (56-40-6) + 1-bromomethyl-4-nitro-benzene (100-11-8) → 4-nitro-3-phenyl-L-alanine (949-99-5) + (R)-4-nitro-phenylalanine (56613-61-7)

Conditions	Yield
Stage #1: glycine With pyridine-2-carboxylic acid(2-benzoyl-phenyl)-amide; sodium methylate; nickel(II) nitrate In methanol for 0.333333h; Heating; Stage #2: 1-bromomethyl-4-nitro-benzene With sodium hydroxide; (R)-2-amino-2'-hydroxy-1,1'-binaphthyl In dichloromethane at 20℃; for 0.0666667h; Stage #3: With hydrogenchloride In methanol; water Heating;

3-(4-nitrophenyl)-2-oxopropanoic acid (38335-24-9) → 4-nitro-3-phenyl-L-alanine (949-99-5)

Conditions	Yield
With Celite; phenylalanine dehydrogenase N145A; potassium chloride; ammonium chloride; 1,4-dihydronicotinamide adenine dinucleotide In ethanol at 20℃; for 18h; pH=8.5;

Boc-Phe(p-NO2)-OH (33305-77-0) → 4-nitro-3-phenyl-L-alanine (949-99-5)

Conditions	Yield
With hydrogenchloride In methanol at 0 - 20℃; for 5h;
With trifluoroacetic acid In dichloromethane

4-nitro-trans-cinnamic acid (882-06-4) → 4-nitro-3-phenyl-L-alanine (949-99-5)

Conditions	Yield
With carbon dioxide; Taxus chinensis phenylalanine aminomutase; ammonia In water pH=10; Kinetics; Enzymatic reaction; optical yield given as %ee; enantioselective reaction;
With ammonium carbamate at 30℃; for 168h; pH=9.1; Time;	n/a

4-nitrophenylalanine (1991-83-9, 2922-40-9, 56613-61-7, 949-99-5) → 4-nitro-3-phenyl-L-alanine (949-99-5) + (R)-4-nitro-phenylalanine (56613-61-7)

Conditions	Yield
With chiral stationary phase including isopropyl-functionalized CF6 In methanol; acetic acid; triethylamine; acetonitrile at 0℃; Purification / work up; Resolution of racemate;
With dichloro bis(acetonitrile) palladium(II); (S)-(1,1'-binaphthalene)-2,2'-diylbis(diphenylphosphine) In aq. phosphate buffer; dichloromethane at 25℃; pH=7; Equilibrium constant; Reagent/catalyst; Solvent; Temperature; Resolution of racemate; enantioselective reaction;
With (S)-2-hydroxy-2'-(3-(N-phenylcarbamoylamino)benzyl)-1,1'-binaphthyl-3-carboxaldehyde In dimethyl sulfoxide Resolution of racemate; stereoselective reaction;	A n/a B n/a

4-amino-L-phenylalanine (943-80-6) → 4-nitro-3-phenyl-L-alanine (949-99-5)

Conditions	Yield
With CmII Enzymatic reaction;
With Streptomyces venezuelae CmlI; oxygen In aq. buffer at 4℃; pH=9; Kinetics; Enzymatic reaction;

(S)-2-(((benzyloxy)carbonyl)amino)-3-(4-nitrophenyl)propanoic acid (17224-90-7) → 4-nitro-3-phenyl-L-alanine (949-99-5)

Conditions	Yield
With ethylenediaminetetraacetic acid; phenylmethylsulphonyl fluoride; water In aq. phosphate buffer at 30℃; Kinetics; Reagent/catalyst; Microbiological reaction; Enzymatic reaction;

N-acetyl-4-nitro-DL-phenylalanine (62561-97-1) → 4-nitro-3-phenyl-L-alanine (949-99-5) + N-acetyl-4-nitro-D-phenylalanine (89615-73-6)

Conditions	Yield
With lipase AS 'Amano' at 35℃; for 24h; pH=6.5; Enzymatic reaction; enantioselective reaction;	A n/a B n/a

4-nitrophenylalanine (1991-83-9, 2922-40-9, 56613-61-7, 949-99-5) → 4-nitro-3-phenyl-L-alanine (949-99-5) + N-acetyl-4-nitro-D-phenylalanine (89615-73-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine / water; N,N-dimethyl-formamide / 20 °C 2: lipase AS 'Amano' / 24 h / 35 °C / pH 6.5 / Enzymatic reaction View Scheme

4-nitro-trans-cinnamic acid (882-06-4) → 4-nitro-3-phenyl-L-alanine (949-99-5) + (R)-4-nitro-phenylalanine (56613-61-7)

Conditions	Yield
With ammonium hydroxide at 30℃; for 0.33h; pH=9.5; Reagent/catalyst; Enzymatic reaction;	A n/a B n/a
With ammonium hydroxide at 30℃; for 22h; pH=9.5; Enzymatic reaction;	A n/a B n/a
With ammonia at 30℃; for 17h; pH=10; Time;	A n/a B n/a

(R)-2-amino-3[(R)-2H]-3(4-nitrophenyl)propanoic acid hydrochloride (1627101-69-2) → 4-nitro-3-phenyl-L-alanine (949-99-5) + (R)-4-nitro-phenylalanine (56613-61-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: E. coli BL21(DE3) whole cells expressing Anabaena variabilis phenylalanine ammonia lyase / aq. buffer / 48 h / 30 °C / pH 8.3 / Enzymatic reaction 2: ammonium hydroxide / 22 h / 30 °C / pH 9.5 / Enzymatic reaction View Scheme

4-nitro-benzoyl chloride (122-04-3) → 4-nitro-3-phenyl-L-alanine (949-99-5) + (R)-4-nitro-phenylalanine (56613-61-7)

Conditions	Yield
Multi-step reaction with 7 steps 1: lithium aluminium deuteride / diethylene glycol dimethyl ether; tert-butyl alcohol / 0.5 h / -78 °C 2: sodium acetate / acetic anhydride / 100 °C 3: methanol / 0.5 h / 20 °C 4: hydrogen; (-)-1,2-bis-[(2R,5R)-2,5-diethylphospholano]benzene(cyclooctadiene)rhodium(I) tetrafluoroborate / methanol / 1.5 h / 5171.62 Torr 5: hydrogenchloride / water; acetone / 7 h / Reflux 6: E. coli BL21(DE3) whole cells expressing Anabaena variabilis phenylalanine ammonia lyase / aq. buffer / 48 h / 30 °C / pH 8.3 / Enzymatic reaction 7: ammonium hydroxide / 22 h / 30 °C / pH 9.5 / Enzymatic reaction View Scheme
Multi-step reaction with 8 steps 1: lithium aluminium deuteride / diethylene glycol dimethyl ether; tert-butyl alcohol / 0.5 h / -78 °C 2: sodium acetate / acetic anhydride / 100 °C 3: methanol / 0.5 h / 20 °C 4: hydrogen; (+)-1,2-bis[(2S,5S)-2,5-diethylphospholano]benzene(cyclooctadiene)rhodium(I) tetrafluoroborate / methanol / 1.5 h / 5171.62 Torr 5: lithium hydroxide / methanol; water; tetrahydrofuran / 2 h / 20 °C 6: cobalt(II) chloride hexahydrate; N-acetyl amino acid racemase G291D/F323Y; D-acylase / aq. buffer / 23 h / 37 °C / pH 8.0 / Enzymatic reaction 7: E. coli BL21(DE3) whole cells expressing Anabaena variabilis phenylalanine ammonia lyase / aq. buffer / 48 h / 30 °C / pH 8.3 / Enzymatic reaction 8: ammonium hydroxide / 22 h / 30 °C / pH 9.5 / Enzymatic reaction View Scheme

α-deuterio-4-nitro-benzaldehyde (94781-50-7) → 4-nitro-3-phenyl-L-alanine (949-99-5) + (R)-4-nitro-phenylalanine (56613-61-7)

Conditions	Yield
Multi-step reaction with 6 steps 1: sodium acetate / acetic anhydride / 100 °C 2: methanol / 0.5 h / 20 °C 3: hydrogen; (-)-1,2-bis-[(2R,5R)-2,5-diethylphospholano]benzene(cyclooctadiene)rhodium(I) tetrafluoroborate / methanol / 1.5 h / 5171.62 Torr 4: hydrogenchloride / water; acetone / 7 h / Reflux 5: E. coli BL21(DE3) whole cells expressing Anabaena variabilis phenylalanine ammonia lyase / aq. buffer / 48 h / 30 °C / pH 8.3 / Enzymatic reaction 6: ammonium hydroxide / 22 h / 30 °C / pH 9.5 / Enzymatic reaction View Scheme
Multi-step reaction with 7 steps 1: sodium acetate / acetic anhydride / 100 °C 2: methanol / 0.5 h / 20 °C 3: hydrogen; (+)-1,2-bis[(2S,5S)-2,5-diethylphospholano]benzene(cyclooctadiene)rhodium(I) tetrafluoroborate / methanol / 1.5 h / 5171.62 Torr 4: lithium hydroxide / methanol; water; tetrahydrofuran / 2 h / 20 °C 5: cobalt(II) chloride hexahydrate; N-acetyl amino acid racemase G291D/F323Y; D-acylase / aq. buffer / 23 h / 37 °C / pH 8.0 / Enzymatic reaction 6: E. coli BL21(DE3) whole cells expressing Anabaena variabilis phenylalanine ammonia lyase / aq. buffer / 48 h / 30 °C / pH 8.3 / Enzymatic reaction 7: ammonium hydroxide / 22 h / 30 °C / pH 9.5 / Enzymatic reaction View Scheme

[4-2H]-4(4-nitrobenzylidene)-2-methyloxazol-5(4H)-one (1627096-62-1) → 4-nitro-3-phenyl-L-alanine (949-99-5) + (R)-4-nitro-phenylalanine (56613-61-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: methanol / 0.5 h / 20 °C 2: hydrogen; (-)-1,2-bis-[(2R,5R)-2,5-diethylphospholano]benzene(cyclooctadiene)rhodium(I) tetrafluoroborate / methanol / 1.5 h / 5171.62 Torr 3: hydrogenchloride / water; acetone / 7 h / Reflux 4: E. coli BL21(DE3) whole cells expressing Anabaena variabilis phenylalanine ammonia lyase / aq. buffer / 48 h / 30 °C / pH 8.3 / Enzymatic reaction 5: ammonium hydroxide / 22 h / 30 °C / pH 9.5 / Enzymatic reaction View Scheme
Multi-step reaction with 6 steps 1: methanol / 0.5 h / 20 °C 2: hydrogen; (+)-1,2-bis[(2S,5S)-2,5-diethylphospholano]benzene(cyclooctadiene)rhodium(I) tetrafluoroborate / methanol / 1.5 h / 5171.62 Torr 3: lithium hydroxide / methanol; water; tetrahydrofuran / 2 h / 20 °C 4: cobalt(II) chloride hexahydrate; N-acetyl amino acid racemase G291D/F323Y; D-acylase / aq. buffer / 23 h / 37 °C / pH 8.0 / Enzymatic reaction 5: E. coli BL21(DE3) whole cells expressing Anabaena variabilis phenylalanine ammonia lyase / aq. buffer / 48 h / 30 °C / pH 8.3 / Enzymatic reaction 6: ammonium hydroxide / 22 h / 30 °C / pH 9.5 / Enzymatic reaction View Scheme

[4-2H]-methyl 2-acetamido-3(4-nitrophenyl)acrylate (1627098-43-4) → 4-nitro-3-phenyl-L-alanine (949-99-5) + (R)-4-nitro-phenylalanine (56613-61-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: hydrogen; (-)-1,2-bis-[(2R,5R)-2,5-diethylphospholano]benzene(cyclooctadiene)rhodium(I) tetrafluoroborate / methanol / 1.5 h / 5171.62 Torr 2: hydrogenchloride / water; acetone / 7 h / Reflux 3: E. coli BL21(DE3) whole cells expressing Anabaena variabilis phenylalanine ammonia lyase / aq. buffer / 48 h / 30 °C / pH 8.3 / Enzymatic reaction 4: ammonium hydroxide / 22 h / 30 °C / pH 9.5 / Enzymatic reaction View Scheme
Multi-step reaction with 5 steps 1: hydrogen; (+)-1,2-bis[(2S,5S)-2,5-diethylphospholano]benzene(cyclooctadiene)rhodium(I) tetrafluoroborate / methanol / 1.5 h / 5171.62 Torr 2: lithium hydroxide / methanol; water; tetrahydrofuran / 2 h / 20 °C 3: cobalt(II) chloride hexahydrate; N-acetyl amino acid racemase G291D/F323Y; D-acylase / aq. buffer / 23 h / 37 °C / pH 8.0 / Enzymatic reaction 4: E. coli BL21(DE3) whole cells expressing Anabaena variabilis phenylalanine ammonia lyase / aq. buffer / 48 h / 30 °C / pH 8.3 / Enzymatic reaction 5: ammonium hydroxide / 22 h / 30 °C / pH 9.5 / Enzymatic reaction View Scheme

(R)-methyl 2-acetamido-3[2H]-3(4-nitrophenyl)propanoate (1627099-40-4) → 4-nitro-3-phenyl-L-alanine (949-99-5) + (R)-4-nitro-phenylalanine (56613-61-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogenchloride / water; acetone / 7 h / Reflux 2: E. coli BL21(DE3) whole cells expressing Anabaena variabilis phenylalanine ammonia lyase / aq. buffer / 48 h / 30 °C / pH 8.3 / Enzymatic reaction 3: ammonium hydroxide / 22 h / 30 °C / pH 9.5 / Enzymatic reaction View Scheme

(S)-methyl 2-acetamido-3-[2H]-3(4-nitrophenyl)propanoate (1627099-66-4) → 4-nitro-3-phenyl-L-alanine (949-99-5) + (R)-4-nitro-phenylalanine (56613-61-7)

Conditions

Yield

Multi-step reaction with 4 steps 1: lithium hydroxide / methanol; water; tetrahydrofuran / 2 h / 20 °C 2: cobalt(II) chloride hexahydrate; N-acetyl amino acid racemase G291D/F323Y; D-acylase / aq. buffer / 23 h / 37 °C / pH 8.0 / Enzymatic reaction 3: E. coli BL21(DE3) whole cells expressing Anabaena variabilis phenylalanine ammonia lyase / aq. buffer / 48 h / 30 °C / pH 8.3 / Enzymatic reaction 4: ammonium hydroxide / 22 h / 30 °C / pH 9.5 / Enzymatic reaction View Scheme

(R)-2-amino-3[(S)-2H]-3(4-nitrophenyl)propanoic acid hydrochloride (1627100-30-4) → 4-nitro-3-phenyl-L-alanine (949-99-5) + (R)-4-nitro-phenylalanine (56613-61-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: E. coli BL21(DE3) whole cells expressing Anabaena variabilis phenylalanine ammonia lyase / aq. buffer / 48 h / 30 °C / pH 8.3 / Enzymatic reaction 2: ammonium hydroxide / 22 h / 30 °C / pH 9.5 / Enzymatic reaction View Scheme

(S)-2-acetamido-3-[2H]-3(4-nitrophenyl)propanoic acid (1627100-31-5) → 4-nitro-3-phenyl-L-alanine (949-99-5) + (R)-4-nitro-phenylalanine (56613-61-7)

Conditions

Yield

Multi-step reaction with 3 steps 1: cobalt(II) chloride hexahydrate; N-acetyl amino acid racemase G291D/F323Y; D-acylase / aq. buffer / 23 h / 37 °C / pH 8.0 / Enzymatic reaction 2: E. coli BL21(DE3) whole cells expressing Anabaena variabilis phenylalanine ammonia lyase / aq. buffer / 48 h / 30 °C / pH 8.3 / Enzymatic reaction 3: ammonium hydroxide / 22 h / 30 °C / pH 9.5 / Enzymatic reaction View Scheme

methyl (S)-2-((tert-butoxycarbonyl)amino)-3-(4-nitrophenyl)propanoate (65615-89-6) → 4-nitro-3-phenyl-L-alanine (949-99-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium hydroxide / tetrahydrofuran; water / 20 °C 2: trifluoroacetic acid / dichloromethane View Scheme

C9H8N2O4 → 4-nitro-3-phenyl-L-alanine (949-99-5) + (R)-4-nitro-phenylalanine (56613-61-7)

Conditions	Yield
With borane-ammonia complex Enzymatic reaction;

methanol (67-56-1) + 4-nitro-3-phenyl-L-alanine (949-99-5) → (S)-4-nitrophenylalanine methyl ester hydrochloride (17193-40-7)

Conditions	Yield
With thionyl chloride at 20℃;	100%
With thionyl chloride at 5 - 45℃;	100%
With thionyl chloride Ambient temperature;	99%

N-(Benzyloxycarbonyloxy)succinimide (13139-17-8) + 4-nitro-3-phenyl-L-alanine (949-99-5) → (S)-2-(((benzyloxy)carbonyl)amino)-3-(4-nitrophenyl)propanoic acid (17224-90-7)

Conditions	Yield
With sodium hydrogencarbonate In water; acetonitrile at 20℃;	100%

4-nitro-3-phenyl-L-alanine (949-99-5) + benzyl chloroformate (501-53-1) → (S)-2-(((benzyloxy)carbonyl)amino)-3-(4-nitrophenyl)propanoic acid (17224-90-7)

Conditions	Yield
With sodium hydroxide; sodium carbonate In water at 6 - 9℃; for 1h;	99.5%
With sodium hydroxide; sodium carbonate In water at 6 - 9℃; for 1h;	99.5%
Stage #1: 4-nitro-3-phenyl-L-alanine; benzyl chloroformate With sodium hydroxide; sodium carbonate In water at 6 - 9℃; for 1h; Stage #2: With hydrogenchloride In water pH=2;	99.5%

methanol (67-56-1) + 4-nitro-3-phenyl-L-alanine (949-99-5) → (L)-p-Nitrophenylalanine methyl ester (81677-60-3)

Conditions	Yield
With thionyl chloride at 0℃; for 2h; Inert atmosphere; Reflux;	98.1%
With thionyl chloride at 0℃; for 1h; Reflux;	91%
With thionyl chloride at 0℃; for 1h; Reflux;	91%

4-nitro-3-phenyl-L-alanine (949-99-5) + toluene-4-sulfonic acid (104-15-4) + benzyl alcohol (100-51-6) → p-nitro-L-phenylalanine benzyl ester toluene-p-sulfonate

Conditions	Yield
In benzene at 120℃; for 12h;	98%
In benzene for 10h; Heating; Yield given;

4-nitro-3-phenyl-L-alanine (949-99-5) + 2,6-Dichlorobenzoyl chloride (4659-45-4) → Nα-(2,6-dichlorobenzoyl)-4-nitro-L-phenylalanine (401906-14-7)

Conditions	Yield
With sodium hydroxide In water; acetone at 10 - 15℃; for 2h; pH=~ 14;	97%
Stage #1: 4-nitro-3-phenyl-L-alanine; 2,6-Dichlorobenzoyl chloride With sodium hydroxide In water; acetone at 15℃; pH=>= 13; Cooling in ice; Stage #2: With hydrogenchloride In water; acetone	95%

4-nitro-3-phenyl-L-alanine (949-99-5) → (S)-3-(4-nitrophenyl)-2-hydroxypropionic acid (33173-27-2)

Conditions	Yield
With sulfuric acid; sodium nitrite In water; acetone at -5 - 20℃; for 18h;	96%
With sulfuric acid; sodium nitrite In water; acetone at -5 - 20℃; for 18h;	96%
With sulfuric acid; water; sodium nitrite at 0 - 20℃;	77%
With sulfuric acid; sodium nitrite at 0 - 20℃;	55%
With sulfuric acid; sodium nitrite

di-tert-butyl dicarbonate (24424-99-5) + 4-nitro-3-phenyl-L-alanine (949-99-5) → Boc-Phe(p-NO2)-OH (33305-77-0)

Conditions	Yield
With sodium hydroxide In 1,4-dioxane; water for 3h; Ambient temperature;	96%
In 1,4-dioxane; water at 0 - 20℃; for 24h; Substitution;	92%
In tetrahydrofuran; sodium hydroxide	88%

dichlorotricarbonylruthenium(II) dimer + 4-nitro-3-phenyl-L-alanine (949-99-5) → tricarbonylchloro(4-nitrophenylalaninato)ruthenium(II)

Conditions	Yield
With sodium methylate In methanol at 20℃; for 24h; Inert atmosphere; Schlenk technique; Darkness;	94.7%

4-nitro-3-phenyl-L-alanine (949-99-5) → (S)-2-amino-3-(4-nitrophenyl)propionic acid ethyl ester hydrochloride (58816-66-3)

Conditions	Yield
Stage #1: ethanol With thionyl chloride at 0 - 20℃; for 0.75h; Stage #2: 4-nitro-3-phenyl-L-alanine Heating / reflux;	92%

4-nitro-3-phenyl-L-alanine (949-99-5) → (2S)-2-amino-3-(2,4-dinitrophenyl)propanoic acid (49607-21-8)

Conditions	Yield
With sulfuric acid; uronium nitrate at 0 - 60℃; for 5h; Temperature; Reagent/catalyst; Time; regioselective reaction;	87.8%

4-nitro-3-phenyl-L-alanine (949-99-5) → 4-amino-L-phenylalanine (943-80-6)

Conditions	Yield
With barium sulfate; hydrogen; palladium	87%
With rosenmund catalyst; hydrogen In water at 20℃; for 3h;	85%
With methanol; aluminum oxide; palladium/alumina Hydrogenation;
With hydrogen; palladium on barium sulfate In water
With hydrogen; Pd-BaSO4 In water

4-nitro-3-phenyl-L-alanine (949-99-5) + N-(9H-fluoren-2-ylmethoxycarbonyloxy)succinimide (82911-69-1) → N-α-FMOC-4-nitro-L-phenylalanine (95753-55-2)

Conditions	Yield
Acylation;	87%
With sodium hydroxide In water; acetonitrile at 20℃; for 3h;	67%

4-nitro-3-phenyl-L-alanine (949-99-5) + N-(benzyloxycarbonyl)succinimide (75315-63-8) → (S)-2-(((benzyloxy)carbonyl)amino)-3-(4-nitrophenyl)propanoic acid (17224-90-7)

Conditions	Yield
With triethylamine In 1,4-dioxane; water	87%

(fluorenylmethoxy)carbonyl chloride (28920-43-6) + 4-nitro-3-phenyl-L-alanine (949-99-5) → N-α-FMOC-4-nitro-L-phenylalanine (95753-55-2)

Conditions	Yield
With sodium carbonate In 1,4-dioxane 0 deg C, then Rt 2 h.;	86%
With sodium carbonate In 1,4-dioxane at 0℃; for 3h;	64%

4-nitro-3-phenyl-L-alanine (949-99-5) → (S)-(-)-2-amino-3-(4-nitrophenyl)propan-1-ol (89288-22-2)

Conditions	Yield
With sodium tetrahydroborate; iodine In tetrahydrofuran at 70℃; for 18h;	86%
With lithium borohydride; chloro-trimethyl-silane In tetrahydrofuran at 0 - 20℃;	68%
With sodium tetrahydroborate; iodine In tetrahydrofuran at 60℃; for 20h;	67%

bromoacetic acid tert-butyl ester (5292-43-3) + 4-nitro-3-phenyl-L-alanine (949-99-5) → 2-(bis-2-tert-butoxycarbonylmethylamino)-3-(4-nitrophenyl)propanoic acid (1619224-40-6)

Conditions	Yield
Stage #1: 4-nitro-3-phenyl-L-alanine With potassium carbonate In acetonitrile for 0.5h; Inert atmosphere; Stage #2: bromoacetic acid tert-butyl ester In acetonitrile for 18h; Inert atmosphere; Reflux;	85%

N-tertiarybutoxycarbonyl-D-alanine N-hydroxysuccinimide ester (34404-33-6) + 4-nitro-3-phenyl-L-alanine (949-99-5) → Boc-D-Ala-p-NO2Phe-OH

Conditions	Yield
With 4-methyl-morpholine In N,N-dimethyl-formamide for 4h; Ambient temperature;	80%

ethanol (64-17-5) + 4-nitro-3-phenyl-L-alanine (949-99-5) → ethyl (S)-2-amino-3-(4-nitrophenyl)propionate (34276-53-4)

Conditions	Yield
With hydrogenchloride for 3h; Heating;	80%

4-nitro-3-phenyl-L-alanine (949-99-5) + p-[N-(2-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl)-N-(prop-2-ynyl)amino]benzoyl azide (126513-13-1) → N-<4--N-prop-2-ynylamino>benzoyl>-L-3-(4-nitrophenyl)alanine

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide for 20h;	80%

4-nitro-3-phenyl-L-alanine (949-99-5) + 2-oxo-propionic acid (127-17-3) → 3-methyl-5-hydroxy-4-(4-nitrophenyl)-2(5H)-furanone

Conditions	Yield
In water at 80℃; for 24h;	76%

4-nitro-3-phenyl-L-alanine (949-99-5) + 2-Formyl-21,23-dihydro-5,10,15,20-tetraphenylporphyrin (71159-98-3) → 3-(4-nitrophenyl)-2-[(5,10,15,20-tetraphenylporphyrin-2-ylmethyl)amino]propionic acid

Conditions	Yield
Stage #1: 4-nitro-3-phenyl-L-alanine; 2-Formyl-21,23-dihydro-5,10,15,20-tetraphenylporphyrin With sodium cyanoborohydride In tetrahydrofuran; methanol for 24h; Reflux; Stage #2: Heating;	75%

4-nitro-3-phenyl-L-alanine (949-99-5) + acetic anhydride (108-24-7) → N-acetyl-4-nitro-L-phenylalanine (17363-92-7)

Conditions	Yield
With sodium hydroxide In acetone for 1h;	74%
In water

4-nitro-3-phenyl-L-alanine (949-99-5) + ethylene glycol (107-21-1) → 4-nitro-(S)-phenylalanine hydroxyethyl ester hydrochloride

Conditions	Yield
Stage #1: ethylene glycol With hydrogenchloride at 20℃; Stage #2: 4-nitro-3-phenyl-L-alanine at 80 - 85℃; for 2h;	73.9%

4-nitro-3-phenyl-L-alanine (949-99-5) → 2-bromo-4-nitro-L-phenylalanine (1222073-44-0)

Conditions	Yield
With tribromo-isocyanuric acid; sulfuric acid optical yield given as %ee;	73%

4-nitro-3-phenyl-L-alanine (949-99-5) + benzoyl chloride (98-88-4) → (S)-4-nitro-N-benzoyl-phenylalanine (69935-12-2)

Conditions	Yield
With sodium hydroxide In water at 0 - 23℃;	68%
With sodium hydroxide
Stage #1: 4-nitro-3-phenyl-L-alanine; benzoyl chloride With sodium hydroxide at 20℃; for 2h; Cooling with ice; Stage #2: With hydrogenchloride In water pH=5 - 6;

4-nitro-3-phenyl-L-alanine (949-99-5) + {[(tert-butoxycarbonyl)oxy]amino}(phenyl)acetonitrile (80994-44-1) → Boc-Phe(p-NO2)-OH (33305-77-0)

Conditions	Yield
With triethylamine In 1,4-dioxane; water Ambient temperature;	67.2%

2-Oxobutyric acid (600-18-0) + 4-nitro-3-phenyl-L-alanine (949-99-5) → 3-ethyl-5-hydroxy-4-(4-nitrophenyl)-2(5H)-furanone

Conditions	Yield
In water at 80℃; for 24h;	67%

Upstream product

• 110270-80-9 (4-nitro-benzyl)-malonic acid 
• 1627100-31-5 (S)-2-acetamido-3-[²H]-3(4-nitrophenyl)propanoic acid 
• 619-89-6 p-nitrocinnamic acid 
• 63-91-2 L-phenylalanine 
• 81677-60-3 (L)-p-Nitrophenylalanine methyl ester 
• 62561-97-1 N-acetyl-4-nitro-DL-phenylalanine 
• 33305-77-0 Boc-Phe(p-NO₂)-OH 
• 882-06-4 4-nitro-trans-cinnamic acid 
• 1991-83-9 4-nitrophenylalanine 
• 1627100-30-4 (R)-2-amino-3[(S)-²H]-3(4-nitrophenyl)propanoic acid hydrochloride 
• 1627099-66-4 (S)-methyl 2-acetamido-3-[2H]-3(4-nitrophenyl)propanoate 
• 1627099-40-4 (R)-methyl 2-acetamido-3[2H]-3(4-nitrophenyl)propanoate 
• 1627098-43-4 [4-²H]-methyl 2-acetamido-3(4-nitrophenyl)acrylate 
• 1627096-62-1 [4-²H]-4(4-nitrobenzylidene)-2-methyloxazol-5(4H)-one 

Downstream Products

• 61777-05-7 4-(4-nitro-benzyl)-oxazolidine-2,5-dione 
• 60666-01-5 (RS)-N-phthaloyl-p-nitrophenylalanine 
• 62561-97-1 N-acetyl-4-nitro-DL-phenylalanine 
• 69935-12-2 (S)-4-nitro-N-benzoyl-phenylalanine 
• 857766-77-9 4-nitro-N-phenylcarbamoyl-phenylalanine 
• 82611-60-7 2-benzyloxycarbonylamino-3-(4-nitrophenyl)propionic acid 
• 144117-81-7 N-(decanoyl)-4-nitro-L-phenylalanine 
• 86937-80-6 2-tert-butoxycarbonylamino-3-(4-nitro-phenyl)-propionic acid 
• 62-23-7 4-nitro-benzoic acid 
• 929217-83-4 3-(4-nitrobenzyl)triethylenetetraamine 
• 929217-82-3 N-(2-aminoethyl)-glycyl 4-nitriphenylalaninamide 
• 929217-80-1 2-(2-tert-butoxycarbonylamino-acetylamino)-3-(4-nitro-phenyl)-propionic acid methyl ester 
• 929217-81-2 {[1-(2-amino-ethylcarbamoyl)-2-(4-nitro-phenyl)-ethylcarbamoyl]-methyl}-carbamic acid tert-butyl ester 
• 85317-52-8 methyl 2-amino-3-(4-nitrophenyl)propionate 

Relevant articles and documents

A novel phenylalanine ammonia-lyase from Pseudozyma antarctica for stereoselective biotransformations of unnatural amino acids

A novel phenylalanine ammonia-lyase of the psychrophilic yeast Pseudozyma antarctica (PzaPAL) was identified by screening microbial genomes against known PAL sequences. PzaPAL has a significantly different substrate binding pocket with an extended loop (26 aa long) connected to the aromatic ring binding region of the active site as compared to the known PALs from eukaryotes. The general properties of recombinant PzaPAL expressed in E. coli were characterized including kinetic features of this novel PAL with L-phenylalanine (S)-1a and further racemic substituted phenylalanines rac-1b-g,k. In most cases, PzaPAL revealed significantly higher turnover numbers than the PAL from Petroselinum crispum (PcPAL). Finally, the biocatalytic performance of PzaPAL and PcPAL was compared in the kinetic resolutions of racemic phenylalanine derivatives (rac-1a-s) by enzymatic ammonia elimination and also in the enantiotope selective ammonia addition reactions to cinnamic acid derivatives (2a-s). The enantiotope selectivity of PzaPAL with o-, m-, p-fluoro-, o-, p-chloro- and o-, m-bromo-substituted cinnamic acids proved to be higher than that of PcPAL.

A PROCESS FOR THE SYNTHESIS OF MELPHALAN

The invention relates to a process for the preparation of Melphalan (4-[bis(2-5 chloroethyl)amino]-L-phenylalanine of formula (I) said process comprising the reaction of a 4-amino-L-phenylalanine protected at the carboxy and amino aminoacidic groups with an agent able to convert the aromatic amino group into a group of formula: -N(CH2CH2OS(O)nO-)2, wherein n is 1 or 2 followed by conversion of the –-N(CH2CH2OS(O)nO-)2 group into a -N(CH2CH2Cl)2 group. The invention also provides novel intermediates useful for the preparation of Melphalan.

Bi-enzymatic Conversion of Cinnamic Acids to 2-Arylethylamines

The conversion of carboxylic acids, such as acrylic acids, to amines is a transformation that remains challenging in synthetic organic chemistry. Despite the ubiquity of similar moieties in natural metabolic pathways, biocatalytic routes seem to have been overlooked for this purpose. Herein we present the conception and optimisation of a two-enzyme system, allowing the synthesis of β-phenylethylamine derivatives from readily-available ring-substituted cinnamic acids. After characterisation of both parts of the reaction in a two-step approach, a set of conditions allowing the one-pot biotransformation was optimised. This combination of a reversible deaminating and irreversible decarboxylating enzyme, both specific for the amino acid intermediate in tandem, represents a general method by which new strategies for the conversion of carboxylic acids to amines could be designed.