Chemical Properties
white to off-white powder
Uses
4-Fluoro-L-phenylalanine is a substrate for tyrosine hydroxylase (TH) that has been used to study the regulation of that enzyme.
Definition
ChEBI: A L-phenylalanine derivative that is L-phenylalanine in which the hydrogen at position 4 on the benzene ring is replaced by a fluoro group.
Synthesis
General procedure for the synthesis of benzophenone, (S)-2-amino-3-(4-fluorophenyl)propanoic acid and (R)-2-amino-3-(4-fluorophenyl)propanoic acid from 4-fluorophenylpyruvic acid and 2,2-diphenylglycine: To a 5 mL reaction vial fitted with a magnetic stirring bar was added 3-cyclohexyl-2-oxypropanoic acid (1j) (0.0510 g, 0.30 mmol ), 2,2-diphenylglycine (2) (0.0681 g, 0.30 mmol), chiral pyridoxamine 6 g (0.0195 g, 0.030 mmol), and MeOH-H2O (8:2, 3.0 mL). The reaction mixture was stirred at 20 °C for 3 days. Subsequently, the reaction mixture was transferred to a 25 mL round-bottomed flask and MeOH was added until all solids were completely dissolved. Next, silica gel (0.50 g) was added. After removal of the solvent by reduced pressure distillation at 20 °C, the resulting residue was separated by silica gel column chromatography (eluent ratio EtOH/ethyl acetate/25-28% ammonia = 100:58:16) to afford compound 3j (0.0401 g, 78% yield, 52% ee) as a white solid. To determine the enantiomeric excess of 3b-k, the compounds were first converted to N-benzoylmethyl esters by treatment with thionyl chloride in methanol followed by reaction with benzoyl chloride and then analyzed by HPLC. For the determination of the enantiomeric excess of 3a, it was analyzed by HPLC after conversion to methyl ester by treatment with CH2N2 in methanol.
Purification Methods
It is recrystallised from aqueous EtOH. The (R)-N-acetyl derivative has m 142-145o, [] D -38.6o (c 8, EtOH). [Bennett & Nieman J Am Chem Soc 72 1800 1950, Beilstein 14 III 1268.]
References
[1] Tetrahedron Letters, 2016, vol. 57, # 41, p. 4612 - 4615
