479065-00-4

Usage

Uses

Used in Pharmaceutical Industry:
(S)-3-(P-METHYLPHENYL)-BETA-ALANINE is used as a building block for the synthesis of novel drugs and pharmaceutical compounds, leveraging its structural similarity to beta-alanine to create new therapeutic agents.
Used in Material Science:
(S)-3-(P-METHYLPHENYL)-BETA-ALANINE is utilized in the development of new materials and chemical products, taking advantage of its unique chemical properties to innovate in material design and synthesis.
Research and Development:
(S)-3-(P-METHYLPHENYL)-BETA-ALANINE is employed in ongoing research to explore its potential uses and applications in various fields, as scientists seek to understand and harness its properties for future advancements.

InChI:InChI=1/C10H13NO2/c1-7-2-4-8(5-3-7)9(11)6-10(12)13/h2-5,9H,6,11H2,1H3,(H,12,13)/t9-/m0/s1

Upstream product

• 141-82-2 malonic acid 
• 104-87-0 4-methyl-benzaldehyde 
• 64-17-5 ethanol 
• 1866-39-3 trans-p-methylcinnamic acid 
• 7803-49-8 hydroxylamine 
• 227473-86-1 3-(p-methylphenyl)-3-hydroxyaminopropionic acid 
• 143407-59-4 2-(2-amino-2-p-tolyl)ethyl-2-oxazoline 
• 21405-59-4 3-(4-methylphenyl)-2-carboxy-2-propenoic acid 
• 21161-19-3 (+/-)-4-(p-tolyl)-2-azetidinone 
• 1866-39-3 4-methylcinnamic acid 
• 94104-32-2 ethyl 3-amino-3-(4-tolyl)propionate 
• 198959-38-5 3-amino-3-(4-methylphenyl)propionic acid methyl ester 
• 27835-00-3 ethyl (4-methylbenzoyl)acetate 
• 1991-87-3 4-methyl-L-phenylalanine 

Downstream Products

• 61752-37-2 3-hydroxy-3-(4'-methylphenyl)propionic acid 
• 219813-90-8 β-D-Phe(4-ME)-OEt 
• 101367-15-1 methyl β-phthalimido-β-(4-methylphenyl)propionate 
• 1307987-76-3 (3S)-3-amino-3-p-tolylpropanamide 

Relevant academic research and scientific papers

Base-induced Sommelet–Hauser rearrangement of N-(α-(2-oxyethyl)branched)benzylic glycine ester-derived ammonium salts via a chelated intermediate

The base-induced Sommelet–Hauser (S–H) rearrangement of N-(α-branched)benzylic glycine ester-derived ammonium salts 1 was investigated. When the α-branched substituent was a simple alkyl, such as a methyl or butyl, desired S–H rearrangement product 2 was obtained in low yield with formation of the [1,2] Stevens rearranged 4 and Hofmann eliminated products 5 and 6. However, when the α-branched substituent had a 2-oxy moiety, such as 2-acetoxyethyl or 2-benzoyloxyethyl, the yields of 2 were improved. These results could be explained by formation of chelated intermediate C that stabilizes the carbanionic ylide, and the subsequent initial dearomative [2,3] sigmatropic rearrangement would be accelerated. The existence of C was supported by mechanistic experiments. This enhancement effect is not very strong or effective; however, it will expand the synthetic usefulness of ammonium ylide rearrangements.

Glutamate as an Efficient Amine Donor for the Synthesis of Chiral β- and γ-Amino Acids Using Transaminase

A recyclable glutamate amine donor system employing transaminase (TA), glutamate dehydrogenase (GluDH) and mutant formate dehydrogenase (FDHm) was developed, wherein amine donor Glu was regenerated using GluDH and thereby circumvented the inhibition of TA by α-ketoglutarate. Various enantiopure β-, γ-amino acids, and amines were successfully synthesized with high conversions and excellent enantiomeric excess using this system.

Synthesis, molecular docking and biological evaluation of novel phthaloyl derivatives of 3-amino-3-aryl propionic acids as inhibitors of Trypanosoma cruzi trans-sialidase

In the last two decades, trans-sialidase of Trypanosoma cruzi (TcTS) has been an important pharmacological target for developing new anti-Chagas agents. In a continuous effort to discover new potential TcTS inhibitors, 3-amino-3-arylpropionic acid derivatives (series A) and novel phthaloyl derivatives (series B, C and D) were synthesized and molecular docking, TcTS enzyme inhibition and determination of trypanocidal activity were carried out. From four series obtained, compound D-11 had the highest binding affinity value (?11.1 kcal/mol) compared to reference DANA (?7.8 kcal/mol), a natural ligand for TS enzyme. Furthermore, the 3D and 2D interactions analysis of compound D-11 showed a hydrogen bond, π-π stacking, π-anion, hydrophobic and Van der Waals forces with all important amino acid residues (Arg35, Arg245, Arg314, Tyr119, Trp312, Tyr342, Glu230 and Asp59) on the active site of TcTS. Additionally, D-11 showed the highest TcTS enzyme inhibition (86.9% ± 5) by high-performance ion exchange chromatography (HPAEC). Finally, D-11 showed better trypanocidal activity than the reference drugs nifurtimox and benznidazole with an equal % lysis (63 ± 4 and 65 ± 2 at 10 μg/mL) and LC50 value (52.70 ± 2.70 μM and 46.19 ± 2.36 μM) on NINOA and INC-5 strains, respectively. Therefore, D-11 is a small-molecule with potent TcTS inhibition and a strong trypanocidal effect that could help in the development of new anti-Chagas agents.

Synthesis and biological evaluation of 3-phenyl-3-aryl carboxamido propanoic acid derivatives as small molecule inhibitors of retinoic acid 4-hydroxylase (CYP26A1)

All-trans-retinoic acid (ATRA), the biologically active metabolite of vitamin A, is used medicinally for the treatment of hyperproliferative diseases and cancers. However, it is easily metabolized. In this study, the leading compound S8 was found based on virtual screening. To improve the activity of the leading compound S8, a series of novel S8 derivatives were designed, synthesized and evaluated for their in vitro biological activities. All of the prepared compounds showed that substituting the 5-chloro-3-methyl-1-phenyl-1H-pyrazole group for the 2-tertbutyl-5-methylfuran scaffold led to a clear increase in the biological activity. The most promising compound 32, with a CYP26A1 IC50 value of 1.36 μM (compared to liarozole (IC50 = 2.45 μM) and S8 (IC50 = 3.21 μM)) displayed strong inhibitory and differentiation activity against HL60 cells. In addition, the study focused on the effect of β-phenylalanine, which forms the coordination bond with the heme of CYP26A1. These studies suggest that the compound 32 can be used as an appropriate candidate for future development.

The bacterial ammonia lyase EncP: A tunable biocatalyst for the synthesis of unnatural amino acids

Enzymes of the class I lyase-like family catalyze the asymmetric addition of ammonia to arylacrylates, yielding high value amino acids as products. Recent examples include the use of phenylalanine ammonia lyases (PALs), either alone or as a gateway to deracemization cascades (giving (S)- or (R)-α-phenylalanine derivatives, respectively), and also eukaryotic phenylalanine aminomutases (PAMs) for the synthesis of the (R)-β-products. Herein, we present the investigation of another family member, EncP from Streptomyces maritimus, thereby expanding the biocatalytic toolbox and enabling the production of the missing (S)-β-isomer. EncP was found to convert a range of arylacrylates to a mixture of (S)-α- and (S)-β-arylalanines, with regioselectivity correlating to the strength of electron-withdrawing/-donating groups on the ring of each substrate. The low regioselectivity of the wild-type enzyme was addressed via structure-based rational design to generate three variants with altered preference for either α- or β-products. By examining various biocatalyst/substrate combinations, it was demonstrated that the amination pattern of the reaction could be tuned to achieve selectivities between 99:1 and 1:99 for β:α-product ratios as desired.

Structure activity relationships of αv integrin antagonists for pulmonary fibrosis by variation in aryl substituents

Antagonism of αvβ6 is emerging as a potential treatment of idiopathic pulmonary fibrosis based on strong target validation. Starting from an αvβ3 antagonist lead and through simple variation in the nature and position of the aryl substituent, the discovery of compounds with improved αvβ6 activity is described. The compounds also have physicochemical properties commensurate with oral bioavailability and are high quality starting points for a drug discovery program. Compounds 33S and 43E1 are pan αv antagonists having ca. 100 nM potency against αvβ3, αvβ5, αvβ6, and αvβ8 in cell adhesion assays. Detailed structure activity relationships with these integrins are described which also reveal substituents providing partial selectivity (defined as at least a 0.7 log difference in pIC50 values between the integrins in question) for αvβ3 and αvβ5.

Mechanism-inspired engineering of phenylalanine aminomutase for enhanced β-regioselective asymmetric amination of cinnamates

Turn to switch: A mutant of phenylalanine aminomutase was engineered that can catalyze the regioselective amination of cinnamate derivatives (see scheme, red) to, for example, β-amino acids. This regioselectivity, along with the X-ray crystal structures, suggests two distinct carboxylate binding modes differentiated by Cβi￡Cipso bond rotation, which determines if β- (see scheme) or α-addition takes place. Copyright

Development of a commercial process for (S)-β-phenylalanine (1)

The development of a commercial manufacturing route for (S)-β-phenylalanine 8, a key pharmaceutical building block, is described. The different approaches which were investigated, based on catalytic asymmetric hydrogenation of enamide intermediates and on biocatalysis using acylase and lipase hydrolyses, are compared. The lipase resolution route was chosen for scale-up, and the final two-step process, based on readily available raw materials, is shown to be robust at full manufacturing scale

Mechanistic, mutational, and structural evaluation of a taxus phenylalanine aminomutase

The structure of a phenylalanine aminomutase (TcPAM) from Taxus canadensis has been determined at 2.4 A resolution. The active site of the TcPAM contains the signature 4-methylidene-1H-imidazol-5(4H)-one prosthesis, observed in all catalysts of the class I lyase-like family. This catalyst isomerizes (S)-α-phenylalanine to the (R)-β-isomer by exchange of the NH 2/H pair. The stereochemistry of the TcPAM reaction product is opposite of the (S)-β-tyrosine made by the mechanistically related tyrosine aminomutase (SgTAM) from Streptomyces globisporus. Since TcPAM and SgTAM share similar tertiary- and quaternary-structures and have several highly conserved aliphatic residues positioned analogously in their active sites for substrate recognition, the divergent product stereochemistries of these catalysts likely cannot be explained by differences in active site architecture. The active site of the TcPAM structure also is in complex with (E)-cinnamate; the latter functions as both a substrate and an intermediate. To account for the distinct (3R)-β-amino acid stereochemistry catalyzed by TcPAM, the cinnamate skeleton must rotate the C1-Cα and C ipso-β bonds 180° in the active site prior to exchange and rebinding of the NH2/H pair to the cinnamate, an event that is not required for the corresponding acrylate intermediate in the SgTAM reaction. Moreover, the aromatic ring of the intermediate makes only one direct hydrophobic interaction with Leu-104. A L104A mutant of TcPAM demonstrated an ～1.5-fold increase in kcat and a decrease in KM values for sterically demanding 3′-methyl-α-phenylalanine and styryl-α-alanine substrates, compared to the kinetic parameters for TcPAM. These parameters did not change significantly for the mutant with 4′-methyl-α-phenylalanine compared to those for TcPAM.(Figure Presented)

Stereoselective chemoenzymatic preparation of β-amino esters: Molecular modelling considerations in lipase-mediated processes and application to the synthesis of (S)-dapoxetine

A wide range of optically active 3-amino-3-arylpropanoic acid derivatives have been prepared by means of a stereoselective chemoenzymatic route. The key step is the kinetic resolution of the corresponding β-amino esters. Although the enzymatic acylations of the amino group with ethyl methoxyacetate showed synthetically useful enantioselectivities, the hydrolyses of the ester group catalyzed by lipase from Pseudomonas cepacia have been identified as the optimal processes concerning both activity and enantioselectivity. The enantiopreference of this lipase in these reactions has been explained, at the molecular level, by using a fragment-based approach in which the most favoured binding site for a phenyl ring and the most stable conformation of the 3-aminopropanoate core nicely match the (S)-configuration of the major products. The conversion and enantioselectivity values of the enzymatic reactions have been compared in order to understand the influence of the different substitution patterns present in the phenyl ring. This chemoenzymatic route has been successfully applied to the preparation of a valuable intermediate in the synthesis of (S)-dapoxetine, which has been chemically synthesised in excellent optical purity.