Α-aminocarboxylic Acids Research Articles

Asymmetric Transfer Hydrogenation as a Key Step in the Synthesis of the Phosphonic Acid Analogs of Aminocarboxylic Acids.

α-Aminophosphonic acids have a remarkably broad bioactivity spectrum. They can function as highly efficient transition state mimics for a variety of hydrolytic and angiotensin-converting enzymes, which makes them interesting target structures for synthetic chemists. In particular, the phosphonic acid analogs to α-aminocarboxylic acids (Pa AAs) are potent enzyme inhibitors, but many of them are only available by chiral or enzymatic resolution; sometimes only one enantiomer is accessible, and several have never been prepared in enantiopure form at all. Today, a variety of methods to access enantiopure α-aminophosphonic acids is known but none of the reported approaches can be generally applied for the synthesis of Pa AAs. Here we show that the phosphonic acid analogs of many (proteinogenic) α-amino acids become accessible by the catalytic, stereoselective asymmetric transfer hydrogenation (ATH) of α-oxo-phosphonates. The highly enantioenriched (enantiomeric excess (ee) ≥ 98 %) α-hydroxyphosphonates obtained are important pharmaceutical building blocks in themselves and could be easily converted to α-aminophosphonic acids in most studied cases. Even stereoselectively deuterated analogs became easily accessible from the same α-oxo-phosphonates using deuterated formic acid (DCO2 H).

Multi-functionalized Cellulosic Biomass by Plasma-Assisted Bonding of α-Amino Carboxylic Acid to Enhance the Removal of Ibuprofen in Aqueous Solution

The present study concerns the removal of ibuprofen (IBP) from aqueous medium using glycine grafted plasma-modified cocoa shell as an effective and promising sorbent. The plasma pretreatment prior to the grafting process creates hydroxyl (–OH), carbonyl (–CO) and carboxyl (–COOH) groups, which were used as binder sites for glycine graft immobilization. The grafting technique was successful as an IR spectra of grafted biosorbent exhibited specific functional groups (N–H, C–N, –OH, C=O, COOH), which were characteristics of newly formed atomic bonds. The attachment to biomass was made through a single glycine and a glycine dipeptide esterified. The results of the removal tests demonstrated that the amounts of IBP uptake at equilibrium were higher with glycine grafted biomass (BG) than un-grafted, so going from 15.24 to 19.88 mg/g for initial 20 mg/L IBP and from 23.18 to 26.98 mg/g for 30 mg/L IBP. Amongst the tested kinetics model to predict adsorption behavior of the experimental results, the Avrami fractional-order model was the most suitable. The values of ΔH° and ΔG° suggested a spontaneous and exothermic process, which is typical for physical interaction in accordance with the Liu best-fitted isotherm model.

Indian producers call for a 40% tariff on imports of Chinese TiO2

New derivatives of 1-[(1-ethoxymethylene)amino]imidazol-5(4H)-one and 1,2,4-triazin-6(5H)-one were synthesized via reactions of optically active α-aminocarboxylic acid hydrazides and triethyl orthoesters in xylene. The factors influencing the formation of the unexpected five-membered products and attempts to elucidate the mechanism are discussed.

The Chemistry of 4-(dicyanomethylene)-3-methyl-l-phenyl-2-pyrazoline-5-ones as a Privileged Scaffold in the Synthesis of Heterocycles.

The reactivity of 4-(dicyanomethylene)-3-methyl-l-phenyl-2-pyrazoline-5-one DCNP 1 and its derivatives makes it valuable as a building block for the synthesis of heterocyclic compounds like pyrazolo- imidazoles, -thiazoles, spiropyridines, spiropyrroles, spiropyrans, and others. As a number of publications have reported on the reactivity of DCNP and its derivatives, we compiled some features of this interesting molecule. This article aims to review the preparation of DCNP, its reactivity, and application in heterocyclic and dyes synthesis. In this review, we have provided an overview of recent progress in the chemistry of DCNP and its significance in the synthesis of various classes of heterocyclic compounds and dyes. The unique reactivity of DCNP offers unprecedentedly mild reaction conditions for the generation of versatile cynomethylene dyes from a wide range of precursors, including amines, α-aminocarboxylic acids, their esters, phenols, malononitriles, and azacrown ethers. We anticipate that more innovative transformations involving DCNP will continue to emerge in the near future.

Syntheses of Enantiopure 1,2-Ethylenediamines with Tethered Secondary Amines of the Formula H2NCH2CH[(CH2) n NHMe]NH2 (n = 1–4) from α-Amino Acids: New Agents for Asymmetric Catalysis

Tris(hydrochloride) adducts of the title compounds­ are prepared from the inexpensive α-amino acids H2N(C=O)CH2CH(NH2)CO2H, HO(C=O)(CH2) n′CH(NH2)CO2H (n′ = 1, 2), and H2N(CH2)4CH(NH2)CO2H, respectively (steps/overall yield = 5/32%, 7/30%, 7/33%, 5/38%). The NH2 group that is remote from the secondary amine is installed via BH3 reduction of an amide [–(C=O)NR2] derived­ from an α-amino carboxylic acid. The MeNHCH2 units are introduced by BH3 reductions of alkyl carbamate [RO(C=O)NHCH2–; R = Et, t-Bu] or amide [MeHN(C=O)–] moieties.

Boron-Catalyzed α-Amination of Carboxylic Acids.

A boron-catalyzed α-amination of simple carboxylic acids was developed. Catalytically generated boron enolates of carboxylic acids reacted with an electrophilic aminating reagent, diisopropylazodicarboxylate, to provide amino acid derivatives. The catalysis afforded not only α-monosubstituted glycine derivatives but also α,α-disubstituted derivatives. The resulting α-aminocarboxylic acid was easily converted to carboxylic acid derivatives. Extension to a catalytic asymmetric variant was possible by introducing a chiral ligand on the boron catalyst.

Synthesis of β-Nitro α-Amino Carboxylic Acids by an Aza-Henry Reaction

Synthesis of β-Nitro α-Amino Carboxylic Acids by an Aza-Henry Reaction

New matrix metalloproteinase inhibitors based on γ-fluorinated α-aminocarboxylic and α-aminohydroxamic acids

Matrix metalloproteinases (MMPs) are involved in a number of physiological as well as pathological processes such as atherosclerosis and tumorigenesis, where an up-regulation of MMPs is predominant. Fluorinated analogues of the hydroxamate-based non-peptidic broad-spectrum MMP inhibitor (MMPI) CGS 27023A were synthesized and inhibition potencies for MMP-2 and MMP-9 in the nanomolar range were measured using fluorimetric in vitro assays. The inhibition potencies of the herein reported fluorinated MMPIs were comparable or even superior in some cases to their non-fluorinated analogues. In contrast to the lead structure, both enantiomers of fluorinated MMPs were almost equally potent. Modelling studies suggest that the core α-amino hydroxamic acid residues appear to influence the relative potencies via specific inhibitor-peptidase interactions, including short fluorine–hydrogen contacts, within the enzyme’s pockets. The binding of the essential hydroxamate group to the zinc ion is rather unaffected by the rest of the molecule. In contrast, the corresponding α-aminocarboxylic acid derivatives are 103 times less potent or were even inactive.

Use of In Situ Generated Nitrosocarbonyl Compounds in Catalytic Asymmetric α-Hydroxylation and α-Amination Reactions

Abstract Nitroso compounds are highly fascinating electrophiles as they are able to selectively transfer both the heteroatoms in a variety of oxidation reactions. Bench stable aryl-nitroso compounds are most extensively utilized for this purpose. However, the prominent success of aryl-nitroso chemistry is still immature because of the difficulty in the cleavage of N-aryl bond. Nitrosocarbonyl compounds with easily removable protecting groups (e.g. Boc and Cbz) on the other hand are more attractive reagents. They are highly reactive, easily manipulable, and readily available via the oxidation of N-protected hydroxylamines. However, the transient nature and incompatibility of the catalytic processes with their generation has incarcerated their use mostly in hetero-Diels–Alder and ene reactions. In this account we will summarize our efforts to utilize the nitrosocarbonyl compounds as a source of electrophilic oxygen and nitrogen in a variety of asymmetric carbon–heteroatom bond-forming reactions. The O- vs. N-selectivity can be tuned by switching reaction conditions. Thus, highly functionalized tertiary α-hydroxy and α-amino carboxylic acids, tertiary α-hydroxy phosphonic acid derivatives and β-amino alcohols were synthesized in high yields and high enantioselectivities using nitrosocarbonyl compounds as a source of electrophilic oxygen and nitrogen.

Fluorinated NH-iminophosphonates and iminocarboxylates: novel synthons for the preparation of biorelevant α-aminophosphonates and carboxylates

A convenient synthetic approach to previously unknown N–H α-iminophosphonates and iminotrifluoropropionates was developed. The synthetic potential of N–H iminophosphonates and iminotrifluoropropionates, existing as an equilibrium mixture of E/Z-isomers, was demonstrated by their easy functionalization to afford biorelevant fluorinated α-aminophosphonic and α-aminocarboxylic acid derivatives.

Synthesis of novel 1-[(1-ethoxymethylene)amino]imidazol-5(4H)-ones and 1,2,4-triazin-6(5H)-ones from optically active α-aminocarboxylic acid hydrazides

Abstract New derivatives of 1-[(1-ethoxymethylene)amino]imidazol-5(4 H )-one and 1,2,4-triazin-6(5 H )-one were synthesized via reactions of optically active α-aminocarboxylic acid hydrazides and triethyl orthoesters in xylene. The factors influencing the formation of the unexpected five-membered products and attempts to elucidate the mechanism are discussed.

Syntheses and Highly Enantioselective Fluorescent Recognition of α‐Aminocarboxylic Acid Anions Using Chiral Oxacalix[2]arene[2]bisbinaphthes

The triazine-based bisbinaphthyl crown ethers oxacalix[2]arene[2]bisbinaphthes R-1, R-2, R-3 and S-1, S-2, S-3 were synthesized. The interactions of these compounds with various α-aminocarboxylic acid anions were studied. The crown ethers were found to carry out highly enantioselective fluorescent recognition of α-aminocarboxylic acid anions. It is observed that within a certain concentration range, one enantiomer of the chiral α-aminocarboxylic acid anions can increase the fluorescence intensity of the crown ethers by fivefold to sixfold, whereas the other enantiomer scarcely enhances the fluorescence. Such unusually high enantioselective responses make these crown ethers very attractive as fluorescent sensors in determining the enantiomeric composition of α-aminocarboxylic acid anions.

The reaction of optically active α-aminocarboxylic acid hydrazides with triethyl orthoesters

New derivatives of 2-(1-amino-1-phenylmethyl)-1,3,4-oxadiazole and 1,2,4-triazin-6-one were synthesised in the reactions of optically active α-aminocarboxylic acid hydrazides and triethyl orthoesters in xylene. The electronic and steric effects of substituents at the α position influencing the formation of five- or six-membered products are discussed.

Herbicide and Tobacco Callus Growth Regulated Activity of New Sintesyzed Substances

ABSTRACTConsiderable efforts have been devoted to the synthesis and investigation of biological activity of α-aminophosphonic acids, largely because of their structural analogy with α-aminocarboxylic acids. Several α-aminophosphonic acid derivatives such as the herbicide Roundup is widely used agriculture.Influence of herbicide activity of some new synthesized dimethylphosphinyl substituted α-aminophosphonic acids and their esters on roots growth mono and dicotyledons plants were studiedOur results showed that higher concentration of examinated substances influence length of mono and dicotyledons plant roots.It was obtained that lower concentrations of two substances (10−5–10−6) stimulate plant roots growth.Some of new synthesized substances have showed positive effect on tobacco callus culture growth.

Structurally simple chiral thioureas as chiral solvating agents in the enantiodiscrimination of α-hydroxy and α-amino carboxylic acids

C 2-Symmetrical chiral thioureas ( S, S)- 1 and ( S, S)- 2 were prepared in good yield by the reaction of 2 equiv of inexpensive ( S)-1-phenylethylamine, or the corresponding naphthyl analog, with 1 equiv of thiophosgene in the presence of excess triethylamine. The presence of asymmetric elements in ( S, S)- 1 and ( S, S)- 2, and their capacity to act as receptors for anionic species via hydrogen bonding were exploited in the development of 1H NMR spectroscopic enantiodiscrimination of chiral carboxylic acids. In particular, the diastereomeric complexes derived from thioureas ( S, S)- 1 and ( S, S)- 2 with ammonium salts of the chiral acids gave rise to well separated signals of the α-hydrogens and simple integration provides the corresponding enantiomeric ratios. Furthermore, it was observed that C α–H in the ( R) enantiomers of the chiral α-hydroxy and α-amino carboxylic acids studied in this work consistently appears downfield relative to the same signals in the ( S) enantiomers.

Synthesis of 2‐Oxo‐2,3,5,6‐tetrahydro‐5‐thioxoimidazo[1,2‐c]quinazolines by One‐Pot Cyclization of α‐Aminocarboxylic Esters with 2‐(Isothiocyanato)benzonitrile (ITCB).

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α-Nitro Ketone Synthesis Using N-Acylbenzotriazoles

[Reaction: see text]. Readily available N-acylbenzotriazoles 2a-l (derived from a variety of aliphatic, (hetero)aromatic, and N-protected alpha-amino carboxylic acids) smoothly convert primary 3a-c and alpha-functionalized primary nitroalkanes 3d into the corresponding alpha-nitro ketones 5a-p in yields of 39-86% (average 63%).

Phosphorus-containing Aminocarboxylic Acids: XIV. Synthesis of Analogs of α-Substituted Glutamic Acid

Addition of Schiff bases derived from amino acid esters to appropriate vinylphosphoryl compounds, followed by hydrolysis of the adducts formed gives a series of new α-alkylated phosphorus-containing α-aminocarboxylic acids, viz. phosphonic and phosphinic analogs of glutamic acid.

Reactions of Sodium N‐Benzylideneglycinate with Dialkyl Chlorophosphites: Formation of 1,4‐Bis[α‐(dialkoxyphosphoryl)benzyl]piperazine‐2,5‐diones.

The reactions of sodium N-benzylideneglycinate with dialkyl chlorophosphites gave 1,4-bis[α-(dialkoxyphosphoryl)benzyl]piperazine-2,5-diones, novel phosphorylated derivatives of α-aminocarboxylic acids.

Hydroxylamines and Sulfinamide as Amine Components in the Petasis Boronic Acid—Mannich Reaction: Synthesis of N‐Hydroxy or Alkoxy‐α‐aminocarboxylicacids and N‐(tert‐Butyl sulfinyl)‐α‐amino Carboxylicacids.

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