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

• 4289-95-6 N-formyl-phenylalanine 
• 2018-61-3 (S)-2-acetylamino-3-phenylpropanoic acid 
• 29618-30-2 (S)-N-benzoyl-phenylalanine anilide 
• 7765-11-9 N-chloroacetyl-DL-phenylalanine 
• 2566-22-5 DL-N-benzoylphenylalanine 
• 127984-21-8 D-mandelic acid-L-phenylalanine 
• 93379-76-1 L-phenylalanine hydrazide; dihydrochloride 
• 13505-32-3 N-tosyl-(S)-phenylalanine 
• 55895-89-1 D,L-phenylalanine p-nitrophenyl ester 
• 1161-13-3 N-Cbz-L-Phe 
• 3303-55-7 L-Phe-Leu 
• 5183-07-3 N-Ac-Δ-Phe-Glu 
• 140-29-4 phenylacetonitrile 
• 17186-52-6 H-Phe-NH-tert-butyl hydrochloride 

Downstream Products

• 100610-68-2 (S)-2-(1,1-dioxo-1λ⁶-thiomorpholino)-3-phenyl-propionic acid 
• 17274-89-4 (S)-2-(nicotinamido)-3-phenylpropanoic acid 
• 7524-50-7 methyl (2S)-2-amino-3-phenylpropanoate hydrochloride 
• 78087-68-0 N-(α-acetylamino-cinnamoyl)-L-phenylalanine 
• 56211-79-1 N-(2-carboxy-ethyl)-L-phenylalanine 
• 1170-76-9 Z-Gly-(L)-Phe 
• 350-09-4 N-trifluoroacetyl-L-phenylalanine 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 2547-03-7 N-[2]naphthyloxycarbonyl-L-phenylalanine 
• 7153-00-6 N-[(Ξ)-2-(2,4-dichloro-phenoxy)-propionyl]-L-phenylalanine 
• 7535-54-8 N-cyclopentyloxycarbonyl-L-phenylalanine 
• 949-45-1 (S)-3-phenyl-2-ureido-propionic acid 
• 13053-69-5 Z-L-His-L-Phe 
• 60-12-8 2-phenylethanol 

Relevant articles and documents

Recreating the natural evolutionary trend in key microdomains provides an effective strategy for engineering of a thermomicrobial N-demethylase

N-demethylases have been reported to remove the methyl groups on primary or secondary amines, which could further affect the properties and functions of biomacromolecules or chemical compounds; however, the substrate scope and the robustness of N-demethylases have not been systematically investigated. Here we report the recreation of natural evolution in key microdomains of the Thermomicrobium roseum sarcosine oxidase (TrSOX), an N-demethylase with marked stability (melting temperature over 100 C) and enantioselectivity, for enhanced substrate scope and catalytic efficiency on -C-N-bonds. We obtained the structure of TrSOX by crystallization and X-ray diffraction (XRD) for the initial framework. The natural evolution in the nonconserved residues of key microdomains—including the catalytic loop, coenzyme pocket, substrate pocket, and entrance site—was then identified using ancestral sequence reconstruction (ASR), and the substitutions that accrued during natural evolution were recreated by site-directed mutagenesis. The single and double substitution variants catalyzed the N-demethylation of N-methyl-L-amino acids up to 1800- and 6000-fold faster than the wild type, respectively. Additionally, these single substitution variants catalyzed the terminal N-demethylation of non-amino-acid compounds and the oxidation of the main chain -C-N- bond to a -C=N- bond in the nitrogen-containing heterocycle. Notably, these variants retained the enantioselectivity and stability of the initial framework. We conclude that the variants of TrSOX are of great potential use in N-methyl enantiomer resolution, main-chain Schiff base synthesis, and alkaloid modification or degradation.

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.

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