131683-27-7

Usage

Uses

Used in Pharmaceutical Synthesis:
(S)-3-Amino-2-benzylpropanoic acid is used as a key intermediate in the synthesis of pharmaceuticals for its unique structural features. Its chiral nature allows for the creation of enantiomerically pure compounds, which is crucial in drug development where stereochemistry can significantly impact the efficacy and safety of medications.
Used in Organic Chemistry:
In the realm of organic chemistry, (S)-3-amino-2-benzylpropanoic acid serves as a versatile building block for the construction of more complex organic molecules. Its reactivity and the presence of the benzyl group facilitate various synthetic transformations, making it a valuable component in the synthesis of natural products, agrochemicals, and other specialty chemicals.
Used in Medicinal Research:
(S)-3-Amino-2-benzylpropanoic acid is utilized in medicinal research for its potential biological activities. Researchers explore its interactions with biological targets, such as enzymes and receptors, to understand its pharmacological properties and potential therapeutic applications. This may lead to the discovery of new drugs or the optimization of existing ones.
Used in Chiral Catalysts Development:
Due to its chiral nature, (S)-3-amino-2-benzylpropanoic acid can be employed in the development of chiral catalysts. These catalysts are essential in asymmetric synthesis, where they enable the selective formation of one enantiomer over another, thus contributing to the production of enantiomerically pure compounds with desired biological activities.
Used in Analytical Chemistry:
(S)-3-Amino-2-benzylpropanoic acid can also find applications in analytical chemistry, particularly in the development of chiral stationary phases for chromatographic separations. These phases are crucial for the resolution of enantiomers, allowing for the accurate determination of their concentrations and ratios in various samples, which is important in quality control and pharmacokinetic studies.

Upstream product

• 123761-13-7 (S)-β²hPhe-OMe 
• 2601-10-7 2‐benzyl‐3‐hydroxypropanenitrile 
• 537041-97-7 2-aminomethyl-3-phenyl-N,N-bis-(1-phenyl-ethyl)-propionamide 
• 501330-94-5 (4S)-4-benzyl-2-[(1S)-1-phenylethyl]isoxazolidin-5-one 
• 210345-90-7 (S)-2-(Benzoylamino-methyl)-3-phenyl-propionic acid 
• 183182-04-9 (2S,5S)-1-Benzoyl-5-benzyl-2-tert-butyl-3-methyl-tetrahydro-pyrimidin-4-one 
• 501-52-0 3-Phenylpropionic acid 
• 34880-68-7 2,2,6,6-tetramethyl-4-(2-phenylethylidene)-3,5-dioxa-2,6-disilaheptane 
• 104-52-9 phenylpropyl chloride 
• 261174-46-3 (S)-2-(benzyloxycarbonylaminomethyl)-3-phenylpropanoic acid 
• 1605314-18-8 benzyl (S)-2-benzyl-3-oxo-3-[(3aR,7aR)-2-oxohexahydrobenzo[d]oxazol-3(2H)-yl]propylcarbamate 
• 1605314-16-6 (S)-3-benzyl-4-oxo-4-[(3aR,7aR)-2-oxohexahydrobenzo[d]oxazol-3(2H)-yl]butanoic acid 
• 1605314-14-4 (S)-benzyl 3-benzyl-4-oxo-4-[(3aR,7aR)-2-oxohexahydrobenzo[d]oxazol-3(2H)-yl]butanoate 
• 1240511-81-2 C₁₄H₂₀N₂O₃ 

Downstream Products

• 210345-90-7 (S)-2-(Benzoylamino-methyl)-3-phenyl-propionic acid 
• 203854-62-0 (S)-3-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-benzylpropanoic acid 

Relevant academic research and scientific papers

Chemical Resolution of C, N-Unprotected α-Substituted β-Amino Acids Using Stable and Recyclable Proline-Derived Chiral Ligands

We report the first purely chemical method for the resolution of C,N-unprotected racemic α-substituted β-amino acids (β2-AAs) using thermodynamically stable and recyclable chiral proline-derived ligands. The ligands and racemic β2-AA

Catalytic Asymmetric Synthesis of Unprotected β2-Amino Acids

We report here a scalable, catalytic one-pot approach to enantiopure and unmodified β2-amino acids. A newly developed confined imidodiphosphorimidate (IDPi) catalyzes a broadly applicable reaction of diverse bis-silyl ketene acetals with a silylated aminomethyl ether, followed by hydrolytic workup, to give free β2-amino acids in high yields, purity, and enantioselectivity. Importantly, both aromatic and aliphatic β2-amino acids can be obtained using this method. Mechanistic studies are consistent with the aminomethylation to proceed via silylium-based asymmetric counteranion-directed catalysis (Si-ACDC) and a transition state to explain the enantioselectivity is suggested on the basis of density functional theory calculation.

β2-Homo-amino acid scan of μ-selective opioid tetrapeptide TAPP

TAPP (H-Tyr-d-Ala-Phe-Phe-NH2) is a potent, μ-selective opioid ligand. In order to gain further insights into pharmacophoric features of this tetrapeptide, we have performed a β2-Homo-amino acid (β2hAA) scan of the TAPP sequence. To this aim, 10 novel analogues have been synthesized and evaluated for μ-opioid and δ-opioid receptor affinity as well as for stability in human plasma. The derivatives included compounds in which a (R)- or (S)-β2-Homo-Homologue replaced the amino acids in the TAPP sequence. The derivatives with (R)- or (S)-β2hPhe4 turned out to bind μOR with affinities equal to that of the parent. β2hAAs in position 1 and 3 resulted in rather large affinity decreases, but the change differed depending on the stereochemistry. β2-Homologation in the second position gave derivatives with very poor μOR binding. According to molecular modelling, the presented α/β-peptides adopt a variety of binding poses with their common element being an ionic interaction between a protonable amine of the first residue and Asp147. A feature required for high μOR affinity seems the ability to accommodate the ring in the fourth residue in a manner similar to that found for TAPP. Contrary to what might be expected, several compounds were significantly less stable in human plasma than the parent compound.

Trans-hexahydrobenzoxazolidinones in the enantioselective synthesis of β2-amino acids containing proteinogenic side chains

The use of enantiopure trans-hexahydrobenzoxazolidinones as chiral auxiliaries in the enantioselective synthesis of two β2-amino acids containing proteinogenic side chains (β2-hPhenylalanine and β2-hLysine), in both enantiomeric forms, is described. Absolute configurations were assigned on the basis of X-ray diffraction analysis and chemical correlation methods.

β-aminopeptidase-catalyzed biotransformations of β2- dipeptides: Kinetic resolution and enzymatic coupling

We have previously shown that the β-aminopeptidases BapA from Sphingosinicella xenopeptidilytica and DmpA from Ochrobactrum anthropi can catalyze reactions with non-natural β3-peptides and β3-amino acid amides. Here we report that these exceptional enzymes are also able to utilize synthetic dipeptides with N-terminal β2-amino acid residues as substrates under aqueous conditions. The suitability of a β2-peptide as a substrate for BapA or DmpA was strongly dependent on the size of the Cα substituent of the N-terminal β2-amino acid. BapA was shown to convert a diastereomeric mixture of the β2-peptide H-β2hPhe- β2hAla-OH, but did not act on diastereomerically pure β2,β3-dipeptides containing an N-terminal β2-homoalanine. In contrast, DmpA was only active with the latter dipeptides as substrates. BapA-catalyzed transformation of the diastereomeric mixture of H-β2hPhe-β2hAla-OH proceeded along two highly S-enantioselective reaction routes, one leading to substrate hydrolysis and the other to the synthesis of coupling products. The synthetic route predominated even at neutral pH. A rise in pH of three log units shifted the synthesis-to-hydrolysis ratio (vS/vH) further towards peptide formation. Because the equilibrium of the reaction lies on the side of hydrolysis, prolonged incubation resulted in the cleavage of all peptides that carried an N-terminal β-amino acid of S configuration. After completion of the enzymatic reaction, only the S enantiomer of β2-homophenylalanine was detected (ee>99% for H-(S)-β2-hPhe-OH, E>500); this confirmed the high enantioselectivity of the reaction. Our findings suggest interesting new applications of the enzymes BapA and DmpA for the production of enantiopure β2-amino acids and the enantioselective coupling of N-terminal β2-amino acids to peptides.

Asymmetric synthesis of β2-amino acids: 2-substituted-3-aminopropanoic acids from N-acryloyl SuperQuat derivatives

Conjugate addition of lithium dibenzylamide to (S)-N(3)-acryloyl-4- isopropyl-5,5-dimethyloxazolidin-2-one (derived from l-valine) and alkylation of the resultant lithium β-amino enolate provides, after deprotection, a range of (S)-2-alkyl-3-aminopropanoic acids in good yield and high ee. Alternatively, via a complementary pathway, conjugate addition of a range of secondary lithium amides to (S)-N(3)-(2′-alkylacryloyl)-4-isopropyl-5,5- dimethyloxazolidin-2-ones, diastereoselective protonation with 2-pyridone, and subsequent deprotection furnishes a range of (R)-2-alkyl- and (R)-2-aryl-3-aminopropanoic acids in good yield and high ee. Additionally, the boron-mediated aldol reaction of β-amino N-acyl oxazolidinones is a highly diastereoselective method for the synthesis of a range of β-amino- β′-hydroxy N-acyl oxazolidinones. The Royal Society of Chemistry.

Nitrile biotransformations for the practical synthesis of highly enantiopure azido carboxylic acids and amides, 'click' to functionalized chiral triazoles and chiral β-amino acids

Under very mild conditions, biotransformations of racemic azido nitriles using Rhodococcus erythropolis AJ270, a nitrile hydratase/amidase-containing microbial whole-cell catalyst, afforded highly enantiopure, (R)-α-arylmethyl- and (+)-α-cyclohexylmethyl-β-azidopropanoic acids and their (S)- and (-)-carboxamide derivatives in excellent yields. The resulting functionalized chiral organoazides were converted in a straightforward fashion to a pair of antipodes of α-benzyl-β-amino acids (R)-13 and (S)-13. Azido carboxamide (S)-11a and azido carboxylic acid (R)-12a underwent 'click' reactions with diethyl acetylenedicarboxylate and phenylacetylene to produce functionalized chiral triazoles 14 and 15, respectively. The easy preparation of the starting nitrile substrates, highly efficient and enantioselective biotransformation reactions, and versatile utility of the resulting functionalized azido carboxylic acids and amide derivatives, render this method very attractive and practical in organic synthesis.

Efficient synthesis of enantiomerically pure β2-amino acids via chiral isoxazolidinones

We report a practical and scalable synthetic route for the preparation of α-substituted β-amino acids (β2-amino acids). Michael addition of a chiral hydroxylamine, derived from α-methylbenzylamine, to an α-alkylacrylate followed by cyclization gives a diastereomeric mixture of α-substituted isoxazolidinones. These diastereomers are separable by column chromatography. Subsequent hydrogenation of the purified isoxazolidinones followed by Fmoc protection affords enantiomerically pure Fmoc-β2-amino acids, which are useful for β-peptide synthesis. This route provides access to both enantiomers of a protected β2-amino acid.

Enantioselective synthesis of β-amino acids Part 13. Diastereoselective alkylation of dianions derived from chiral analogs of β-aminopropanoic acid containing the α-phenylethyl group

Inexpensive acryloyl chloride was converted in 91% overall yield to two derivatives of β-alanine, (R,R,R)-and (R,R,S)-6, containing two chiral auxiliaries. C-Alkylation of (R,R,R)- and (R,R,S)-6 via a dianion derivative, was performed by direct metallation with 2.2 equiv. of lithium hexamethyldisilazane (LHMDS) in THF at - 78°. C-Alkylation of (R,R,S)-6-Li2 ('matched' pair of chiral auxiliaries) afforded the mono-alkylated products 8-11 in 29-96% yield and 54-95% stereoselectivity. Employment of LiCl as an additive generally increased stereoselectivities, whereas the effect of HMPA as a cosolvent was erratic. Chemical correlation of the major diastereoisomer from the alkylation reactions with (S)-α-alkyl-β-alanine (12-15) showed that addition of the electrophile preferentially takes place on the enolate's Si-face. This conclusion is also supported by molecular-modeling studies (ab initio HF/3-21G), which indicate that the lowest-energy conformation for (R,R,S)-6-Li2 presents the more sterically hindered Re-face of the enolate. The theoretical studies also predict a determining role for N-Li-O chelation in (R,R,S)-6-Li2, giving rise to an interesting 'ion-triplet' configuration for the dilithium dianion.

β2- And β3-Peptides with Proteinaceous Side Chains: Synthesis and Solution Structures of Constitutional Isomers, a Novel Helical Secondary Structure and the Influence of Solvation and Hydrophobic Interactions on Folding

Enantiomerically pure β-amino-acid derivatives with the side chains of Ala, Val, and Leu in the 2- or 3-position (β2- and β3-amino acids, resp.), as well as with substituents in both the 2- and 3-positions (β2,3-amino acids, of like-configuration) have been prepared (compounds 8-17) and incorporated (by stepwise synthesis and fragment coupling, intermediates 24-34) into β-hexa-, β-hepta-, and β-dodecapeptides (1-17). The new and some of the previously prepared β-peptides (35-39) showed NH/ND exchange rates (in MeOH at room temperature) with τ1/2 values of up to 60 days, unrivalled by short chain α-peptides. All β-peptides 1-7 were designed to be able to attain the previously described 31-helical structure (Figs. 1 and 2). CD Measurements (Fig. 4), indicating a new secondary structure of certain β-peptides constructed of β2- and β3-amino acids, were confirmed by detailed NMR solution-structure analyses: a β2-heptapeptide (2c) and a β2,3-hexapeptide (7c) have the 31-helical structure (Figs. 6 and 7), while to a β2/β3-hexapeptide (4) with alternating substitution pattern H-(β2-Xaa-β3-Xaa)3-OH a novel, unusual helical structure (in (D5)pyridine, Fig. 8; and in CD3OH, Figs. 9 and 10) was assigned, with a central ten-membered and two terminal twelve-membered H-bonded rings, and with C=O and N-H bonds pointing alternatively up and down along the axis of the helix (Fig. 11). Thus, for the first time, two types of β-peptide turns have been identified in solution. Hydrophobic interactions of and hindrance to solvent accessibility by the aliphatic side chains are discussed as possible factors influencing the relative stability of the two types of helices.