80126-53-0

Basic information

• Product Name: 2-Methylphenyl-L-alanine
• Synonyms: 2-METHYL-L-PHENYLALANINE;L-2-METHYLPHE;L-2-METHYLPHENYLALANINE;H-PHE(2-ME)-OH;H-O-ME-PHE-OH;(2S)-2-amino-3-(2-methylphenyl)propanoic acid;L-2-Me-Phe-OH;2-Methylphenyl-L-alanine
• CAS NO: 80126-53-0
• Molecular Formula: C₁₀H₁₃NO₂
• Molecular Weight: 179.22
• EINECS: 145-896-5
• Product Categories: Amino Acids;Phenylalanine analogs and other aromatic alpha amino acids;Amino Acid Derivatives;a-amino
• Mol File: 80126-53-0.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 326.2 °C at 760 mmHg
• Flash Point: 151.1 °C
• Appearance: /
• Density: 1.165 g/cm³
• Refractive Index: 1.561
• Storage Temp.: Store at -15°C
• PKA: 2.25±0.10(Predicted)
• CAS DataBase Reference: 2-Methylphenyl-L-alanine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Methylphenyl-L-alanine(80126-53-0)
• EPA Substance Registry System: 2-Methylphenyl-L-alanine(80126-53-0)

Safety Data

• Hazard Codes: Xi
• Hazardous Substances Data: 80126-53-0(Hazardous Substances Data)

Usage

Chemical Properties

White powder

InChI:InChI=1/C10H13NO2/c1-7-5-3-4-6-8(7)10(2,11)9(12)13/h3-6H,11H2,1-2H3,(H,12,13)/t10-/m1/s1

Synthetic route

2-Oxo-3-o-tolyl-propionic acid anion → (S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0)

Conditions	Yield
With L-glutamic acid; pyridoxal 5'-phosphate In water at 40℃; for 12h; E.coli Aspartate transaminase, pH 8;	30%

(E)-3-(2-methylphenyl)acrylic acid (939-57-1, 2373-76-4, 41397-71-1) → (S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0)

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 ammonia at 30℃; for 17h; pH=10; Time; Reagent/catalyst;	n/a

2-([(18)F]-fluoromethyl)-L-phenylalanine (1111643-38-9) → (S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0)

Conditions	Yield
With water at 50℃; pH=7;

2-methylcinnamic acid (2373-76-4) → (S)-3-amino-3-(2-methylphenyl)propionic acid (736131-48-9) + (S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0)

Conditions	Yield
With ammonium bisulphate; EncP-E293M variant at 55℃; for 22h; pH=8.3; Enzymatic reaction; stereoselective reaction;	A n/a B n/a

2-methylcinnamic acid (2373-76-4) → (R)-3-amino-3-(2-methylphenyl)propionic acid + (S)-3-amino-3-(2-methylphenyl)propionic acid (736131-48-9) + (S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0)

Conditions	Yield
With ammonium bisulphate; EncP wild type enzyme at 55℃; for 22h; pH=8.3; Enzymatic reaction; stereoselective reaction;	A n/a B n/a C n/a

3-amino-3-(2-methylphenyl)propanoic acid (68208-16-2) → (R)-3-amino-3-(2-methylphenyl)propionic acid + (E)-3-(2-methylphenyl)acrylic acid (939-57-1, 2373-76-4, 41397-71-1) + (S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0)

Conditions	Yield
With phenylalanine ammonia α-lyase from Anabaena variabilis; phenylalanine ammonia lyase from Streptomyces maritimus In aq. buffer at 30℃; for 24h; pH=8; Reagent/catalyst; Resolution of racemate; Enzymatic reaction; enantioselective reaction;

(E)-3-(2-methylphenyl)acrylic acid (939-57-1, 2373-76-4, 41397-71-1) → (S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0) + 2-(fluoromethyl)-D-phenylalanine

Conditions	Yield
Stage #1: (E)-3-(2-methylphenyl)acrylic acid With ammonium hydroxide; phenylalanine ammonia-lyase from Anabaena variabilis N347A mutant In aq. buffer at 35℃; for 12h; pH=8.5; Stage #2: With borane-ammonia complex; L-amino acid deaminase from Proteus mirabilis In aq. buffer at 35℃; for 12h; pH=8.5; stereoselective reaction;	A n/a B n/a

2-amino-3-(2-methylphenyl)propanoic acid (22888-51-3) → (S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: phenylalanine ammonia-lyase from Pseudozyma antarctica yeast / aq. buffer / 168 h / 30 °C / pH 8.5 / Resolution of racemate 2: ammonia / 17 h / 30 °C / pH 10 View Scheme

di-tert-butyl dicarbonate (24424-99-5) + (S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0) → Nα-tert-butyloxycarbonyl-2'-methyl-L-phenylalanine (80102-29-0, 139558-50-2, 114873-05-1)

Conditions	Yield
With triethylamine In 1,4-dioxane; water at 20℃; for 2h;	89.2%

1,10-Phenanthroline (66-71-7) + sodium perchlorate + (S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0) + palladium dichloride → [Pd(L-(o-methyl)phenylalaninate)(1,10-phenanthroline)]ClO4

Conditions	Yield
With NaOH; HCl In hydrogenchloride; methanol addn. of 2 equiv. aminoacid to PdCl2 (in 1 M HCl), pH-adjustment to 6-7 (aq. NaOH), addn. of 1 equiv. phenanthroline (in aq. MeOH), stirring at 40°C overnight, pptn. on addn. of aq. NaClO4;	89%

1,10-Phenanthroline (66-71-7) + copper(II) perchlorate hexahydrate + (S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0) → [Cu(L-(o-methyl)phenylalaninate)(1,10-phenanthroline)]ClO4 * H2O

Conditions	Yield
With NaOH In methanol; water addn. of 1 equiv. aminoacid (in 1 M NaOH) to equimolar mixt. of Cu-salt and phenanthroline (in 50% aq. MeOH), stirring at room temp. to dissoln.; crystn., collection, recrystn. (aq. MeOH); elem. anal.;	86%

(S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0) → 2-(fluoromethyl)-D-phenylalanine

Conditions	Yield
With D-glucose; nicotinamide adenine dinucleotide phosphate; ammonium chloride In aq. buffer at 20℃; for 24h; pH=9; Microbiological reaction; enantioselective reaction;	83%
With D-glucose; D-amino acid aminotransferase from Bacillus sp mutant T242G; L-aminoacid deaminase from Proteus mirabilis In aq. phosphate buffer at 37℃; for 4h; pH=8; Enzymatic reaction; enantioselective reaction;	n/a

potassium cyanate (590-28-3) + (S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0) → (S)-5-(2-methylbenzyl)imidazolidine-2,4-dione

Conditions	Yield
With hydrogenchloride In water for 5h; Reflux;	67%

(S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0) → (R)-3-amino-3-(2-methylphenyl)propionic acid

Conditions	Yield
With phenylalanine aminomutase at 31℃; for 2h; Enzyme kinetics;

(S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0) → Nα-tert-butyloxycarbonyl-2'-methyl-L-phenylalanyl-L-phenylalanylamide (943726-70-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 89.2 percent / triethylamine / dioxane; H2O / 2 h / 20 °C 2: 97 percent / diisopropylethylamine; benzotriazol-1-yloxytrispyrrolidinophosphonium*PF6 / dimethylformamide / 4 h / 20 °C View Scheme

(S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0) → C19H23N3O2*HCl

Conditions	Yield
Multi-step reaction with 3 steps 1: 89.2 percent / triethylamine / dioxane; H2O / 2 h / 20 °C 2: 97 percent / diisopropylethylamine; benzotriazol-1-yloxytrispyrrolidinophosphonium*PF6 / dimethylformamide / 4 h / 20 °C 3: HCl / dioxane / 0.5 h / 20 °C View Scheme

(S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0) → Nα-tert-butyloxycarbonyl-L-tyrosyl-L-prolyl-2'-methyl-L-phenylalanyl-L-phenylalanylamide (943726-76-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: 89.2 percent / triethylamine / dioxane; H2O / 2 h / 20 °C 2: 97 percent / diisopropylethylamine; benzotriazol-1-yloxytrispyrrolidinophosphonium*PF6 / dimethylformamide / 4 h / 20 °C 3: HCl / dioxane / 0.5 h / 20 °C 4: 289 mg / diisopropylethylamine; benzotriazol-1-yloxytrispyrrolidinophosphonium*PF6 / dimethylformamide / 4 h / 20 °C View Scheme

(S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0) → Nα-tert-butyloxycarbonyl-2',6'-dimethyl-L-tyrosyl-L-prolyl-2'-methyl-L-phenylalanyl-L-phenylalanylamide (943726-77-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: 89.2 percent / triethylamine / dioxane; H2O / 2 h / 20 °C 2: 97 percent / diisopropylethylamine; benzotriazol-1-yloxytrispyrrolidinophosphonium*PF6 / dimethylformamide / 4 h / 20 °C 3: HCl / dioxane / 0.5 h / 20 °C 4: 266 mg / diisopropylethylamine; benzotriazol-1-yloxytrispyrrolidinophosphonium*PF6 / dimethylformamide / 4 h / 20 °C View Scheme

(S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0) → L-tyrosyl-L-prolyl-2'-methyl-L-phenylalanyl-L-phenylalanylamide

Conditions

Yield

Multi-step reaction with 5 steps 1: 89.2 percent / triethylamine / dioxane; H2O / 2 h / 20 °C 2: 97 percent / diisopropylethylamine; benzotriazol-1-yloxytrispyrrolidinophosphonium*PF6 / dimethylformamide / 4 h / 20 °C 3: HCl / dioxane / 0.5 h / 20 °C 4: 289 mg / diisopropylethylamine; benzotriazol-1-yloxytrispyrrolidinophosphonium*PF6 / dimethylformamide / 4 h / 20 °C 5: trifluoroacetic acid; anisole / 1 h / 20 °C View Scheme

(S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0) → 2',6'-dimethyl-L-tyrosyl-L-prolyl-2'-methyl-L-phenylalanyl-L-phenylalanylamide

Conditions

Yield

Multi-step reaction with 5 steps 1: 89.2 percent / triethylamine / dioxane; H2O / 2 h / 20 °C 2: 97 percent / diisopropylethylamine; benzotriazol-1-yloxytrispyrrolidinophosphonium*PF6 / dimethylformamide / 4 h / 20 °C 3: HCl / dioxane / 0.5 h / 20 °C 4: 266 mg / diisopropylethylamine; benzotriazol-1-yloxytrispyrrolidinophosphonium*PF6 / dimethylformamide / 4 h / 20 °C 5: trifluoroacetic acid; anisole / 1 h / 20 °C View Scheme

(S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0) + palladium dichloride → [Pd(L-(o-methyl)phenylalaninate)2]

Conditions	Yield
With NaOH; HCl In hydrogenchloride addn. of 2 equiv. ligand to PdCl2, pH-adjustment to 6-7 (aq. NaOH);

(S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0) → (E)-3-(2-methylphenyl)acrylic acid (939-57-1, 2373-76-4, 41397-71-1)

Conditions	Yield
With Taxus phenylalanine aminomutase at 31℃; for 1h; Kinetics; Enzymatic reaction;

(S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0) → 3-(4-methoxybenzyl)-5-(2-methylbenzyl)imidazolidine-2,4-dione

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride / water / 5 h / Reflux 2: potassium carbonate / N,N-dimethyl-formamide / 12 h / 20 °C View Scheme

acetic acid tert-butyl ester (540-88-5) + (S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0) → (S)-tert-butyl 2-amino-3-(o-tolyl)propanoate

Conditions	Yield
With perchloric acid In water at 20 - 30℃; for 16h; Inert atmosphere;

ethanol (64-17-5) + (S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0) → C12H17NO2 (1212275-99-4)

Conditions	Yield
With thionyl chloride at 0 - 75℃; for 3h;

(S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0) → N-((2S)-4-chloro-3-hydroxy-1-(o-tolyl)butan-2-yl)benzamide

Conditions	Yield
Multi-step reaction with 4 steps 1.1: thionyl chloride / 3 h / 0 - 75 °C 2.1: triethylamine / dichloromethane / 0 - 20 °C 3.1: lithium diisopropyl amide / tetrahydrofuran / 0.17 h / -78 - -70 °C 3.2: -78 - -65 °C 4.1: sodium tetrahydroborate View Scheme

(S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0) → N-((2S,3R)-4-chloro-3-hydroxy-1-(o-tolyl)butan-2-yl)benzamide

Conditions	Yield
Multi-step reaction with 4 steps 1.1: thionyl chloride / 3 h / 0 - 75 °C 2.1: triethylamine / dichloromethane / 0 - 20 °C 3.1: lithium diisopropyl amide / tetrahydrofuran / 0.17 h / -78 - -70 °C 3.2: -78 - -65 °C 4.1: C38H40ClN2O3RhS; / dichloromethane / 1 h / 25 °C / Schlenk technique View Scheme

(S)-2-amino-3-(o-tolyl)propanoic acid (80126-53-0) → (S)-N-(4-chloro-3-oxo-1-(o-tolyl)butan-2-yl)benzamide

Conditions	Yield
Multi-step reaction with 3 steps 1.1: thionyl chloride / 3 h / 0 - 75 °C 2.1: triethylamine / dichloromethane / 0 - 20 °C 3.1: lithium diisopropyl amide / tetrahydrofuran / 0.17 h / -78 - -70 °C 3.2: -78 - -65 °C View Scheme

Upstream product

• 22888-51-3 2-amino-3-(2-methylphenyl)propanoic acid 
• 939-57-1 (E)-3-(2-methylphenyl)acrylic acid 
• 68208-16-2 3-amino-3-(2-methylphenyl)propionic acid 
• 2373-76-4 2-methylcinnamic acid 
• 1111643-38-9 2-([⁽¹⁸⁾F]-fluoromethyl)-L-phenylalanine 

Downstream Products

• 80102-29-0 N^α-tert-butyloxycarbonyl-2'-methyl-L-phenylalanine 
• 943726-77-0 N^α-tert-butyloxycarbonyl-2',6'-dimethyl-L-tyrosyl-L-prolyl-2'-methyl-L-phenylalanyl-L-phenylalanylamide 
• 943726-76-9 N^α-tert-butyloxycarbonyl-L-tyrosyl-L-prolyl-2'-methyl-L-phenylalanyl-L-phenylalanylamide 
• 943726-70-3 N^α-tert-butyloxycarbonyl-2'-methyl-L-phenylalanyl-L-phenylalanylamide 
• 752198-38-2 (R)-3-amino-3-(2-methylphenyl)propionic acid 
• 1212275-99-4 C₁₂H₁₇NO₂ 
• 1991-86-2 2-(fluoromethyl)-D-phenylalanine 
• 939-57-1 (E)-3-(2-methylphenyl)acrylic acid 

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.

Kinetic Resolution of Aromatic β-Amino Acids Using a Combination of Phenylalanine Ammonia Lyase and Aminomutase Biocatalysts

An enzymatic strategy for the preparation of (R)-β-arylalanines employing phenylalanine aminomutase and ammonia lyase (PAM and PAL) enzymes has been demonstrated. Candidate PAMs with the desired (S)-selectivity from Streptomyces maritimus (EncP) and Bacillus sp. (PabH) were identified via sequence analysis using a well-studied template sequence. The newly discovered PabH could be linked to the first ever proposed biosynthesis of pyloricidin-like secondary metabolites and was shown to display better β-lyase activity in many cases. In spite of this, a method combining the higher conversion of EncP with a strict α-lyase from Anabaena variabilis (AvPAL) was found to be more amenable, allowing kinetic resolution of five racemic substrates and a preparative-scale reaction with >98% (R) enantiomeric excess. This work represents an improved and enantiocomplementary method to existing biocatalytic strategies, allowing simple product separation and modular telescopic combination with a preceding chemical step using an achiral aldehyde as starting material. (Figure presented.).

Mechanistic approach of the difference in non-enzymatic hydrolysis rate between the L and D enantiomers of no-carrier added 2-[18F] fluoromethyl-phenylalanine

No-carrier added (n.c.a.) 2-[18F]fluoromethyl-l-phenylalanine was found to be very sensitive to hydrolysis in aqueous solutions. This problem was solved partially by the addition of calcium ions (0.04M), increasing the shelf-life to at least 6h. In this paper the defluorination reaction was studied in detail to elucidate its mechanism. Therefore, L and D enantiomers of 2-[18F]FMP and 4-[18F]FMP were synthesized, as well as 2-[18F]fluoromethyl-phenethylamine and 4-[18F] fluoromethyl-phenethylamine, both decarboxylated 'mimetic' molecules of the amino acid analogues. Radiosynthesis, using a customized Scintomics automatic synthesis hotboxthree module, resulted in a high overall yield and a radiochemical purity of >99%. The defluorination rates of all compounds were studied by HPLC. The L enantiomer of n.c.a 2-[18F]FMP defluorinated seven times faster than the D enantiomer and 2-[18F]fluoromethyl- phenethylamine. Both enantiomers of 4-[18F]FMP and 4-[ 18F]fluoromethyl-phenethylamine were stable. From these data, the reaction mechanism, involving two distinct intramolecular interactions, was derived. First, the interaction between the amine and the benzylic fluorine weakens the carbon-fluorine bond. Secondly, the formation of a second hydrogen bridge between the carboxyl group and one of the benzylic hydrogen atoms renders the fluorine atom even more susceptible to hydrolysis. The latter interaction induces an additional chiral center. The probability of its formation differs considerably between L and D enantiomers of n.c.a. 2-[18F]FMP, which explains the difference in hydrolysis rate. Copyright