18125-46-7

Usage

Uses

Used in Pharmaceutical Industry:
4-Fluoro-D-Phenylalanine is used as a building block for the preparation of new peptidomimetics. Its unique chemical properties allow for the development of novel compounds with potential therapeutic applications, particularly in the area of drug design and development.
Used in Research and Development:
In the field of research and development, 4-Fluoro-D-Phenylalanine serves as an important compound for studying the effects of fluorination on the properties and functions of amino acids. This knowledge can be applied to the design of new drugs and the understanding of protein structures and interactions.
Used in Chemical Synthesis:
4-Fluoro-D-Phenylalanine is also utilized in chemical synthesis, where its fluorinated structure can be exploited to create a variety of new compounds with different properties and potential applications in various industries, such as pharmaceuticals, agrochemicals, and materials science.

Upstream product

• 69216-82-6 (R)-N-acetyl-p-fluorophenylalanine 
• 1994-30-5 Sodium; 3-(4-fluoro-phenyl)-2-oxo-propionate 
• 7761-30-0 sodium 3-(4-fluorophenyl)-2-oxopropionate 
• 404-32-0 DL-Z-4-F-Phe-OH 
• 459-46-1 4-Fluorobenzyl bromide 
• 51-65-0 4-Fluorophenylalanine 
• 103-81-1 Benzeneacetamide 
• 64282-12-8 4-fluoro-DL-phenylalanine methyl ester hydrochloride 
• 133919-66-1 4-fluoro-(RS)-phenylalaninamide hydrochloride 
• 459-32-5 4-fluorocinnamic acid 
• 3060-50-2 2,2-diphenylglycine 
• 207910-84-7 (Z)-3-(4-fluorophenyl)-2-hydroxyacrylic acid 
• 459-57-4 4-fluorobenzaldehyde 
• 459-32-5 (E)-4-fluorocinnamic acid 

Downstream Products

• 117467-73-9 (R)-(N-benzyloxycarbonyl)-p-fluorophenylalanine 
• 200267-65-8 (R)-2-Amino-3-(4-fluorophenyl)-1-propanol 
• 874336-38-6 C₂₅H₃₁FN₂O₅ 
• 874440-04-7 C₂₀H₂₃FN₂O₃ 
• 1351469-20-9 C₄₃H₅₅FN₄O₇ 
• 1351469-21-0 C₃₁H₄₁FN₄O₅ 
• 203732-76-7 C₁₆H₁₆FNO₂ 
• 874336-40-0 C₅₀H₆₁FN₄O₉ 
• 1351469-17-4 C₄₂H₅₅FN₄O₇ 
• 874336-42-2 (R)-2-((R)-2-((S)-2-(((R)-2-(2-(3-aminopropyl)phenoxy)propyl)-amino)-2-cyclopropyl-N-methylacetamido)propanamido)-3-(4-fluorophenyl)propanoic acid 
• 874336-39-7 C₂₀H₂₃FN₂O₃*ClH 
• 874336-43-3 C₃₀H₃₉FN₄O₄*ClH 
• 842131-33-3 ulimorelin 
• 1047666-75-0 C₃₁H₃₉FN₄O₄ 

Relevant academic research and scientific papers

Reconstruction of Hyper-Thermostable Ancestral L-Amino Acid Oxidase to Perform Deracemization to D-Amino Acids

L-amino acid oxidases (LAAOs) with broad substrate specificity can be used in the deracemization of D,L-amino acids (D,L-AAs) to their D-enantiomers. Hyper-thermostable LAAO (HTAncLAAO) was designed through a combination of manual sequence data mining and ancestral sequence reconstruction. Soluble expression of HTAncLAAO (>50 mg/L) can be achieved using an E. coli system. HTAncLAAO, which recognizes seven L-AAs as substrates, exhibits extremely high thermal stability and long-term stability; the t1/2 value was 95 °C and 99 % ee, D-enantiomer). These results suggest that HTAncLAAO is an excellent biocatalyst to perform this deracemization.

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.

Deracemization and stereoinversion to aromatic d-amino acid derivatives with ancestral l-amino acid oxidase

Enantiomerically pure amino acid derivatives could be foundational compounds for peptide drugs. Deracemization of racemates to l-amino acid derivatives can be achieved through the reaction of evolved d-amino acid oxidase and chemical reductants, whereas deracemization to d-amino acid derivatives has not progressed due to the difficulty associated with the heterologous expression of l-amino acid oxidase (LAAO). In this study, we succeeded in developing an ancestral LAAO (AncLAAO) bearing broad substrate selectivity (13 l-amino acids) and high productivity through an Escherichia coli expression system (50.7 mg/L). AncLAAO can be applied to perform deracemization to d-amino acids in a similar way to deracemization to l-amino acids. In fact, full conversion (>99% ee, d-form) could be achieved for 16 racemates, including nine d,l-Phe derivatives, six d,l-Trp derivatives, and a d,l-phenylglycine. Taken together, we believe that AncLAAO could be a key enzyme to obtain optically pure d-amino acid derivatives in the future.

Engineered Aminotransferase for the Production of d-Phenylalanine Derivatives Using Biocatalytic Cascades

d-Phenylalanine derivatives are valuable chiral building blocks for a wide range of pharmaceuticals. Here, we developed stereoinversion and deracemization biocatalytic cascades to synthesize d-phenylalanine derivatives that contain electron-donating or -withdrawing substituents of various sizes and at different positions on the phenyl ring with a high enantiomeric excess (90 to >99 % ee) from commercially available racemic mixtures or l-amino acids. These whole-cell systems couple Proteus mirabilis l-amino acid deaminase with an engineered aminotransferase that displays native-like activity towards d-phenylalanine, which we generated from Bacillus sp. YM-1 d-amino acid aminotransferase. Our cascades are applicable to preparative-scale synthesis and do not require cofactor-regeneration systems or chemical reducing agents.

One-Pot Enzymatic Synthesis of d-Arylalanines Using Phenylalanine Ammonia Lyase and l-Amino Acid Deaminase

The phenylalanine ammonia-lyase (AvPAL) from Anabaena variabilis catalyzes the amination of substituent trans-cinnamic acid (t-CA) to produce racemic d,l-enantiomer arylalanine mixture owing to its low stereoselectivity. To produce high optically pure d-arylalanine, a modified AvPAL with high d-selectivity is expected. Based on the analyses of catalytic mechanism and structure, the Asn347 residue in the active site was proposed to control stereoselectivity. Therefore, Asn347 was mutated to construct mutant AvPAL-N347A, the stereoselectivity of AvPAL-N347A for d-enantiomer arylalanine was 2.3-fold higher than that of wild-type AvPAL (WtPAL). Furthermore, the residual l-enantiomer product in reaction solution could be converted into the d-enantiomer product through stereoselective oxidation by PmLAAD and nonselective reduction by reducing agent NH3BH3. At optimal conditions, the conversion rate of t-CA and optical purity (enantiomeric excess (eeD)) of d-phenylalanine reached 82% and exceeded 99%, respectively. The two enzymes displayed activity toward a broad range of substrate and could be used to efficiently synthesize d-arylalanine with different groups on the phenyl ring. Among these d-arylalanines, the yield of m-nitro-d-phenylalanine was highest and reached 96%, and the eeD exceeded 99%. This one-pot synthesis using AvPAL and PmLAAD has prospects for industrial application.

Bio-inspired enantioselective full transamination using readily available cyclodextrin

The mimics of vitamin B6-dependent enzymes that catalyzed an enantioselective full transamination in the pure aqueous phase have been realized for the first time through the establishment of a new “pyridoxal 5′-phosphate (PLP) catalyzed non-covalent cyclodextrin (CD)-keto acid inclusion complexes” system, and various optically active amino acids have been obtained.

ANTIBACTERIALS AND/OR MODULATORS OF BIOFILM FORMATION AND METHODS OF USING THE SAME

Amides substituted with aromatic groups were synthesized and some were purified to create enantiomer pure compounds. The compounds were tested to determine their ability to inhibit the growth of bacteria and the formation of biofilms created by bacteria. Some of these compounds were found to be effective antibacterials and to effectively inhibit the formation of biofilms.

A new type of chiral-pyridoxamines for catalytic asymmetric transamination of α-keto acids

A new type of chiral pyridoxamines bearing an adjacent chiral stereocenter has been developed via multi-step synthesis. The pyridoxamines displayed catalytic activity in asymmetric transamination of α-keto acids to give a variety of optically active amino acids in 27–78% yields with 34–62% ee's under very mild conditions. This work provides a synthetic strategy to construct new chiral pyridoxamines using bromopyridine 7 as a key synthon and also represents an early example of the applications of chiral pyridoxamines in asymmetric catalysis.

Single-Biocatalyst Synthesis of Enantiopure d-Arylalanines Exploiting an Engineered d-Amino Acid Dehydrogenase

A practical and efficient biocatalytic synthesis of aromatic d-amino acids has been developed, based on the reductive amination of the corresponding α-keto acids via a recombinant whole cell system composed of an engineered dehydrogenase and cofactor recycling apparatus. The reaction was shown to give excellent enantioselectivity (≥98%) and good yields at the preparative scale across a broad range of substrates. Additionally, the structure of the variant enzyme was solved to allow rationalisation of the observed reaction rates. The engineered whole cell catalyst was also used to mediate the production of d-phenylalanine derivatives from racemic mixtures and cheaper l-amino acids by combining it with an enantiocomplementary deaminase. (Figure presented.).

Influence of the aromatic moiety in α- And β-arylalanines on their biotransformation with phenylalanine 2,3-aminomutase from: Pantoea agglomerans

In this study enantiomer selective isomerization of various racemic α- and β-arylalanines catalysed by phenylalanine 2,3-aminomutase from Pantoea agglomerans (PaPAM) was investigated. Both α- and β-arylalanines were accepted as substrates when the aryl moiety was relatively small, like phenyl, 2-, 3-, 4-fluorophenyl or thiophen-2-yl. While 2-substituted α-phenylalanines bearing bulky electron withdrawing substituents did not react, the corresponding substituted β-aryl analogues were converted rapidly. Conversion of 3- and 4-substituted α-arylalanines happened smoothly, while conversion of the corresponding β-arylalanines was poor or non-existent. In the range of pH 7-9 there was no significant influence on the conversion of racemic α- or β-(thiophen-2-yl)alanines, whereas increasing the concentration of ammonia (ammonium carbonate from 50 to 1000 mM) inhibited the isomerization progressively and decreased the amount of the by-product (i.e. (E)-3-(thiophen-2-yl)acrylic acid was detected). In all cases, the high ee values of the products indicated excellent enantiomer selectivity and stereospecificity of the isomerization except for (S)-2-nitro-α-phenylalanine (ee 92%) from the β-isomer. Substituent effects were rationalized by computational modelling revealing that one of the main factors controlling biocatalytic activity was the energy difference between the covalent regioisomeric enzyme-substrate complexes.