63-91-2

Basic information

• Product Name: L-Phenylalanine
• Synonyms: L(-)-PHENYLALANINE;L-PHENYLALANINE;L-PHE;BETA-PHENYLALANINE;DL-2-AMINO-3-PHENYLPROPANOIC ACID;L-ALPHA-AMINO-BETA-PHENYLPROPIONIC ACID;L-BETA-PHENYLALANINE;L-2-AMINO-3-PHENYLPROPANOIC ACID
• CAS NO: 63-91-2
• Molecular Formula: C₉H₁₁NO₂
• Molecular Weight: 165.19
• EINECS: 200-568-1
• Product Categories: Food and Feed Additive;Amino ACIDS SERIES;API intermediates;Phenylalanine [Phe, F];Amino Acids and Derivatives;Amino Acids 13C, 2H, 15N;alpha-Amino Acids;Amino Acids;Biochemistry;Nutritional Supplements;L-Amino Acids;Amino Acids;Amino Acids & Derivatives;amino
• Mol File: 63-91-2.mol
• Article Data: 445

Chemical Properties

• Melting Point: 270-275 °C (dec.)(lit.)
• Boiling Point: 293.03°C (rough estimate)
• Flash Point: 139.8 °C
• Appearance: White to off-white/powder
• Density: 1.29
• Vapor Pressure: 7.09E-05mmHg at 25°C
• Refractive Index: -34 ° (C=2, H2O)
• Storage Temp.: Store at RT.
• Solubility: H2O: 0.1 M at 20 °C, clear, colorless
• PKA: 2.2(at 25℃)
• Water Solubility: 1-5 g/100 mL at 25 ºC
• Stability: Stable. Incompatible with strong oxidizing agents.
• Merck: 14,7271
• BRN: 1910408
• CAS DataBase Reference: L-Phenylalanine(CAS DataBase Reference)
• NIST Chemistry Reference: L-Phenylalanine(63-91-2)
• EPA Substance Registry System: L-Phenylalanine(63-91-2)

Safety Data

• Hazard Codes: C
• Statements: 36/37/38-34
• Safety Statements: 22-24/25-37/39-45-36/37/39-27-26
• WGK Germany: 3
• RTECS: AY7535000
• F: 10
• TSCA: Yes
• Hazardous Substances Data: 63-91-2(Hazardous Substances Data)

Usage

Description

Phenylalanie is an essential amino acid and it is the precursor of the amino acid tyrosine. The body cannot make phenylalanie but it needs phenylalanie to produce proteins. Thus, human needs to obtain phenylalanie from food. 3 forms of phenylalanie are found in the nature: D-phenylalanine, L-phenylalanine, and DL-phenylalanine. Among these three forms, L-phenylalanine is the natural form found in most foods that containing proteins, including beef, poultry, pork, fish, milk, yogurt, eggs, cheeses, soy products, and certain nuts and seeds. The form of phenylalanine determines its application. It is suggested that L-phenylalanine can strengthen the effect of UVA radiation for people with vitiligo, in which L-phenylalanine may lead to darkening or repigmentation of the white patches, particularly on the face. The neurotransmitters L-phenylalanine affects help reduce hunger, improve memory, lessen the symptoms of ADHD and Parkinson's disease, and ease chronic pain, according to the UMMC research. Thus, L-phenylalanine is used in the manufacture of food and drink products and sold as a nutritional supplement for its reputed analgesic and antidepressant effects. L-phenylalanine is also suggested as an intermediate for anti-cancer drugs. A few small studies showed promise using L-Phenylalanine to manage alcohol withdrawal and ease PMS symptoms. It is also used in artificial sweeteners such as aspartame.

References

[1] http://www.umm.edu/health/medical/altmed/supplement/phenylalanine [2] Xueqin Song , Philip L. Lorenzi , Christopher P. Landowski , Balvinder S. Vig , John M. Hilfinger , Gordon L. Amidon (2005) Amino Acid Ester Prodrugs of the Anticancer Agent Gemcitabine:? Synthesis, Bioconversion, Metabolic Bioevasion, and hPEPT1-Mediated Transport, 2, 157-167.

Chemical Properties

Different sources of media describe the Chemical Properties of 63-91-2 differently. You can refer to the following data:
1. L-Phenylalanine has no odor and a slight bitter taste. It melts with decomposition at about 283°C. The pH of a 1 in 100 solution is between 5.4 and 6.0. FEMA notes this chemical is used in cocoa substitute only.
2. White crystalline powder

Occurrence

Reported found in white bread, macaroni, egg noodles, corn flakes, corn grits, oatmeal, wheat bran, wheat flakes, shredded wheat, barley, brown rice, rye flour, whole grain wheat flour, buttermilk, blue cheese, cheddar cheese, cottage cheese, cream cheese, parmesan cheese, bacon, cured ham, frankfurters, pork sausage, canned red kidney beans, canned sweet corn, canned peas, canned lima beans, canned potatoes, canned asparagus, canned snap beans, canned beets, beef, lamb, fresh ham, veal round, beef liver, chicken, chicken liver, turkey and other natural sources.

Uses

Different sources of media describe the Uses of 63-91-2 differently. You can refer to the following data:
1. phenylalanine is a conditioning agent with greater application in hair care than in skin care preparations. It is also used in suntan products.
2. L-Phenylalanine is an essential amino acid. L-Phenylalanine is biologically converted into L-tyrosine, another one of the DNA-encoded amino acids, which in turn is converted to L-DOPA and further conv erted into dopamine, norepinephrine, and epinephrine. L-Phenylalanine is produced for medical, feed, and nutritional applications such as in the preparation of Aspartame.
3. L-phenylalanine is an amino acid used as a skin-conditioning agent. It has greater use in hair care than in skin care products.

Definition

ChEBI: The L-enantiomer of phenylalanine.

Preparation

From PTS-negative Escherichia coli bioengineered strains.

Synthesis Reference(s)

Canadian Journal of Chemistry, 29, p. 427, 1951 DOI: 10.1139/v51-051The Journal of Organic Chemistry, 30, p. 3414, 1965 DOI: 10.1021/jo01021a035Tetrahedron Letters, 26, p. 2449, 1985 DOI: 10.1016/S0040-4039(00)94850-0

General Description

Odorless white crystalline powder. Slightly bitter taste. pH (1% aqueous solution) 5.4 to 6.

Air & Water Reactions

Water soluble. Aqueous solutions are weak acids.

Reactivity Profile

L-Phenylalanine may be light sensitive. Act as weak acids in solution.

Health Hazard

ACUTE/CHRONIC HAZARDS: When heated to decomposition L-Phenylalanine emits toxic fumes of nitrogen oxides.

Fire Hazard

Flash point data for L-Phenylalanine are not available; however, L-Phenylalanine is probably combustible.

Biochem/physiol Actions

L-Phenylalanine is an essential amino acid. It is significantly involved in the synthesis of neurotransmitters such as dopamine, epinephrine, norepinephrine, l-DOPA (Dihydroxyphenylalanine), melanin and thyroxine. L-Phenylalanine metabolism also results in phenylethylamine, that brings about effect of a stimulant in the brain and enhances mood.

Purification Methods

Likely impurities are leucine, valine, methionine and tyrosine. Crystallise L-phenylalanine from water by adding 4volumes of EtOH. Dry it in vacuo over P2O5. Also crystallise it from saturated refluxing aqueous solutions at neutral pH, or 1:1 (v/v) EtOH/water solution, or conc HCl. It sublimes at 176-184o/0.3mm with 98.7% recovery and unracemised [Gross & Gradsky J Am Chem Soc 77 1678 1955]. [Greenstein & Winitz The Chemistry of the Amino Acids J. Wiley, Vol 3 pp 2156-2175 1961, Beilstein 14 IV 1552.]

InChI:InChI:1S/C9H11NO2/c10-8(9(11)12)6-7-4-2-1-3-5-7/h1-5,8H,6,10H2,(H,11,12)

Synthetic route

methyl (2S)-2-amino-3-phenylpropanoate (2577-90-4) → L-phenylalanine (63-91-2)

Conditions	Yield
With ammonium bicarbonate; water In dichloromethane for 48h; α-chymotrypsin;	100%
With sodium hydroxide In water; ethyl acetate pH=9 - 10;	93%
at 25℃; for 0.833333h; enzyme alcalase from Bacillus licheniforms; pH 8.2;

N-Cbz-L-Phe (1161-13-3) → L-phenylalanine (63-91-2)

Conditions	Yield
With cell extract of Sphingomonas paucimobilis SC 16113 In water at 42℃; for 20h; Enzymatic reaction;	100%
With hydrogen In ethanol for 0.5h;	100%
With palladium on activated charcoal In methanol; ethyl acetate	99%

H-Phe-OEt (3081-24-1) → L-phenylalanine (63-91-2)

Conditions	Yield
With ammonium bicarbonate; water In dichloromethane for 36h; α-chymotrypsin;	100%
With Tris buffer; water at 50℃; Rate constant;
With human valacyclovirase; water at 37℃; pH=7.4; Kinetics; Time; HEPES buffer; Enzymatic reaction;

((prop-2-yn-1-yloxy)carbonyl)-L-phenylalanine (439912-45-5) → L-phenylalanine (63-91-2)

Conditions	Yield
With resin bound tetrathiomolybdate In methanol at 28℃; for 1.5h; ultrasonic bath;	100%

2-oxo-3-(phenyl)propionic acid (156-06-9) → L-phenylalanine (63-91-2)

Conditions	Yield
With formate dehydrogenase; NAD; ammonium formate at 30℃; for 24h; PheDH;	99%
With A-(modified B6)-B-<ω-amino(ethylamino)>-β-cyclodextrin In water at 30℃; for 5h; pH 8.0 (phosphate buffer); Yield given;
With formate dehydrogenase; NAD; ammonium formate at 30℃; for 24h; Mechanism; buffer (pH 8.5); other oxo-acids; PheDH;

phenylalanine amide hydrochloride (108321-83-1) → L-phenylalanine (63-91-2)

Conditions	Yield
With pyridoxal 5'-phosphate monohydrate; cobalt(II) chloride In aq. buffer at 40℃; for 4h; pH=7.0; Enzymatic reaction;	99%

(S)-2-acetylamino-3-phenylpropanoic acid (2018-61-3) → L-phenylalanine (63-91-2)

Conditions	Yield
With pepsin immobilized on terephthalaldehyde functionalized chitosan magnetic nanoparticle In acetonitrile at 20℃; for 48h; pH=2;	98%
With hydrogenchloride
With hydrogen bromide

phenylpyruvate- (620-76-8) → L-phenylalanine (63-91-2)

Conditions	Yield
With ammonium formate; tris hydrochloride; nicotinamide adenine dinucleotide; formate dehydrogenase; phenylalanine dehydrogenase In water at 30℃; for 24h;	98%
With ammonium formate; tris hydrochloride; nicotinamide adenine dinucleotide; phenylalanine and formate dehydrogenase In water at 30℃; for 24h; Equilibrium constant; pH = 8.5;	98%
With L-glutamic acid; pyridoxal 5'-phosphate In water at 40℃; for 12h; E.coli Aspartate transaminase, pH 8;	84%
With L-glutamic acid; E.coli Aspartate transaminase; pyridoxal 5'-phosphate at 40℃; for 12h; enzyme kinetics; pH 8; Miachaelis constant (Km); maximum velocity constant (vmax); further α-keto acids;	84%
With L-glutamine; human glutamine transaminase K at 37℃; pH=7.4; aq. phosphate buffer; Enzymatic reaction;

((S)-1-Cyano-2-phenyl-ethyl)-carbamic acid methyl ester (631921-67-0) → L-phenylalanine (63-91-2)

Conditions	Yield
With hydrogenchloride In water for 7h; Heating;	98%

(S)-2-hydrazinyl-3-phenylpropanoic acid (1202-31-9) → L-phenylalanine (63-91-2)

Conditions	Yield
With hydrogen; nickel In water; acetic acid under 25857.4 Torr;	97%

(S)-2-{1-[4-Nitro-1,3-dioxo-indan-(2E)-ylidene]-ethylamino}-3-phenyl-propionic acid → L-phenylalanine (63-91-2) + 2-[1-Hydrazino-eth-(E)-ylidene]-4-nitro-indan-1,3-dione

Conditions	Yield
With hydrazine hydrate In ethanol for 3h; Ambient temperature;	A n/a B 97%

Phenylalanine (150-30-1) → L-phenylalanine (63-91-2)

Conditions	Yield
With D-amino acid oxidase; E. coli branched-chain amino acid aminotransferase In water at 37℃; for 72h; Tris buffer, pH 8.5, 1mM EDTA, monosodium glutamate, bovine serum albumin, catalase, pyridoxal 5'-phosphate;	96%
With porcine kidney D-amino acid oxidase (EC 1.4.3.3.); sodium cyanoborohydride; flavin adenine dinucleotide In phosphate buffer at 37℃;	82%
With sodium hydroxide; oxygen at 30℃; for 24h; pH=7.3; aq. buffer; Enzymatic reaction; optical yield given as %ee; enantioselective reaction;	44%

N-allyloxycarbonyl-(S)-phenylalanate (90508-20-6) → L-phenylalanine (63-91-2)

Conditions	Yield
With tri-n-butyl-tin hydride; bis-triphenylphosphine-palladium(II) chloride In dichloromethane Ambient temperature;	95%

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) → L-phenylalanine (63-91-2)

Conditions	Yield
With tetradecyl(trihexyl)phosphonium bistriflamide; trifluoroacetic acid at 130℃; for 0.166667h; Ionic liquid;	95%
With methanol; tetrachloromethane at 20℃; for 12h; UV-irradiation;	91%
With trifluoroacetic acid
With ethylenediaminetetraacetic acid; phenylmethylsulphonyl fluoride; water In aq. phosphate buffer at 30℃; Kinetics; Reagent/catalyst; Microbiological reaction; Enzymatic reaction;
With trifluoroacetic acid at 20℃; for 0.25h;

benzyl bromide (100-39-0) → L-phenylalanine (63-91-2)

Conditions	Yield
	95%
Multi-step reaction with 2 steps 1: 1.) LDA / 1.) THF, hexane, from -78 deg C to -20 deg C; 2.) THF, from -78 deg C to -20 deg C, 24 h 2: 92 percent / 1 N aq. HCl / 4 h / Heating View Scheme
Multi-step reaction with 3 steps 1: 1.) sodium bis(trimethylsilyl)amide / 1.) THF, -82 deg C, 40 min, 2.) THF, -82 deg C, 1.5 h 2: 80 percent / trifluoroacetic acid / CH2Cl2 / 4 h 3: 76 percent / H2 / PdCl2 / tetrahydrofuran; ethanol / 29 h / 2172.02 Torr View Scheme
Multi-step reaction with 2 steps 1: 1.) LDA / 1.) THF, -78 deg C, 2.) THF, -78 deg C 2: 85 percent / 6N HCl / 6 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 77 percent / NaN(Si(CH3)3)2 / tetrahydrofuran / 0.67 h / -100 °C 2: 1) TFA; 2) H2 / 2) Pd / 1) CH2Cl2 View Scheme

N-Fmoc L-Phe (35661-40-6) → L-phenylalanine (63-91-2)

Conditions	Yield
With sodium azide In N,N-dimethyl-formamide at 50℃; for 1h; Temperature; Time; Solvent;	95%
Stage #1: N-Fmoc L-Phe With N-ethyl-N,N-diisopropylamine In dichloromethane for 1h; 2-chlorotrityl chloride resin; Stage #2: With piperidine In N,N-dimethyl-formamide for 0.166667h; 2-chlorotrityl chloride resin; Stage #3: With trifluoroacetic acid In dichloromethane for 0.166667h;
With piperidine In N,N-dimethyl-formamide for 0.0333333h; Solvent;

C34H29Cl2N3NiO3 → L-phenylalanine (63-91-2) + (S)-1-benzyl-N-[4-chloro-2-(2-chlorobenzoyl)phenyl]pyrrolidine-2-carboxamide (1616841-99-6)

Conditions	Yield
Stage #1: C34H29Cl2N3NiO3 With hydrogenchloride In 1,4-dioxane; methanol; water at 60℃; Stage #2: In 1,4-dioxane; methanol; water enantioselective reaction;	A 72% B 95%

D-Phenylalaninamide (5241-58-7, 5241-59-8, 17193-31-6, 60058-39-1) + butan-1-ol (71-36-3) → L-phenylalanine (63-91-2)

Conditions	Yield
	94%

(3S,6S,8S,8aS)-3-benzyl-7,7,8a-trimethyl-3,5,6,7,8,8a-hexahydro-2H-6,8-methanobenzo[b][1,4]oxazin-2-one (141895-40-1) → L-phenylalanine (63-91-2)

Conditions	Yield
With hydrogenchloride In tetrahydrofuran at 70℃; for 3h;	93%

(S)-4'-benzyl-9λ4-boraspiro[bicyclo[3.3.1]nonane-9,2'-[1,3,2]oxazaborolidin]-5'-one → L-phenylalanine (63-91-2)

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran; water at 20℃; for 1h; Reagent/catalyst; Temperature; Solvent;	93%
With peracetic acid; disodium hydrogenphosphate In dichloromethane at 20℃; Reagent/catalyst;

Upstream product

• 156-06-9 2-oxo-3-(phenyl)propionic acid 
• 55895-89-1 D,L-phenylalanine p-nitrophenyl ester 
• 1161-13-3 N-Cbz-L-Phe 
• 22839-47-0 L-Asp-L-Phe-OMe 
• 3303-55-7 L-Phe-Leu 
• 5183-07-3 N-Ac-Δ-Phe-Glu 
• 53078-86-7 8--argenate 
• 55379-75-4 2-amino-3-phenylpropanenitrile 
• 73148-70-6 α(L)-aminobenzylacetonitrile 
• 744-59-2 N-benzoylglycyl-L-phenylalanine 
• 99239-98-2 phenylalanine isobutyl ester; hydrochloride 
• 61090-95-7 (S)-2-[(S)-2-(2-{(R)-2-[(S)-2-Amino-3-(4-hydroxy-phenyl)-propionylamino]-propionylamino}-acetylamino)-3-phenyl-propionylamino]-4-methylsulfanyl-butyramide 
• 35590-86-4 (3S,6S)-3-(1-methylethyl)-6-(phenylmethyl)piperazine-2,5-dione 
• 439912-45-5 ((prop-2-yn-1-yloxy)carbonyl)-L-phenylalanine 

Downstream Products

• 100610-68-2 (S)-2-(1,1-dioxo-1λ⁶-thiomorpholino)-3-phenyl-propionic acid 
• 7524-50-7 methyl (2S)-2-amino-3-phenylpropanoate hydrochloride 
• 96789-63-8 N-(o-carboxybenzoyl)-L-phenylalanine 
• 5123-55-7 Nα-phthaloyl-L-phenylalanine 
• 3081-24-1 H-Phe-OEt 
• 350-09-4 N-trifluoroacetyl-L-phenylalanine 
• 404-33-1 N-(N-trifluoroacetyl-glycyl)-L-phenylalanine 
• 35874-27-2 phenylalaninyl adenylate 
• 962-39-0 L-Phenylalanine benzyl ester 
• 83037-88-1 N-(3,5-dinitrobenzoyl)-L-phenylalanine 
• 2577-90-4 methyl (2S)-2-amino-3-phenylpropanoate 
• 34101-09-2 (S)-2-Ethylsulfanylthiocarbonylamino-3-phenyl-propionic acid 
• 71859-28-4 (S)-2-[3-((2R,3S,4R,5R)-2,3,4,5,6-Pentaacetoxy-hexanoyl)-thioureido]-3-phenyl-propionic acid ethyl ester 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 

Relevant articles and documents

Enhanced carboxypeptidase efficacies and differentiation of peptide epimers

Carboxypeptidases enzymatically cleave the peptide bond of C-terminal amino acids. In humans, it is involved in enzymatic synthesis and maturation of proteins and peptides. Carboxypeptidases A and Y have difficulty hydrolyzing the peptide bond of dipeptides and some other amino acid sequences. Early investigations into different N-blocking groups concluded that larger moieties increased substrate susceptibility to peptide bond hydrolysis with carboxypeptidases. This study conclusively demonstrates that 6-aminoquinoline-N-hydroxysuccimidyl carbamate (AQC) as an N-blocking group greatly enhances substrate hydrolysis with carboxypeptidase. AQC addition to the N-terminus of amino acids and peptides also improves chromatographic peak shapes and sensitivities via mass spectrometry detection. These enzymes have been used for amino acid sequence determination prior to the advent of modern proteomics. However, most modern proteomic methods assume that all peptides are comprised of L-amino acids and therefore cannot distinguish L-from D-amino acids within the peptide sequence. The majority of existing methods that allow for chiral differentiation either require synthetic standards or incur racemization in the process. This study highlights the resistance of D-amino acids within peptides to enzymatic hydrolysis by Carboxypeptidase Y. This stereoselectivity may be advantageous when screening for low abundance peptide stereoisomers.

Mechanically Strong Heterogeneous Catalysts via Immobilization of Powderous Catalysts to Porous Plastic Tablets

Main observation and conclusion: We describe a practical and general protocol for immobilization of heterogeneous catalysts to mechanically robust porous ultra-high molecular weight polyethylene tablets using inter-facial Lifshitz-van der Waals Interactions. Diverse types of powderous catalysts, including Cu, Pd/C, Pd/Al2O3, Pt/C, and Rh/C have been immobilized successfully. The immobilized catalysts are mechanistically robust towards stirring in solutions, and they worked well in diverse synthetic reactions. The immobilized catalyst tablets are easy to handle and reused. Moreover, the metal leaching of immobilized catalysts was reduced significantly.

Direct monitoring of biocatalytic deacetylation of amino acid substrates by1H NMR reveals fine details of substrate specificity

Amino acids are key synthetic building blocks that can be prepared in an enantiopure form by biocatalytic methods. We show that thel-selective ornithine deacetylase ArgE catalyses hydrolysis of a wide-range ofN-acyl-amino acid substrates. This activity was revealed by1H NMR spectroscopy that monitored the appearance of the well resolved signal of the acetate product. Furthermore, the assay was used to probe the subtle structural selectivity of the biocatalyst using a substrate that could adopt different rotameric conformations.