Primary Α-amino Acids Research Articles

Enantioselective Michael addition of aldehydes to maleimides catalysed by surface-adsorbed natural amino acids

Chiral hybrid materials obtained by adsorption of primary α-amino acids on the surface of inorganic oxides are economic, recyclable, highly enantioselective heterogeneous catalysts for the Michael addition of aldehydes toN-substituted maleimides.

Regioselectivity and diastereoselectivity of three-component reaction of \u03b1-amino acid, dialkyl acetylenedicarboxylates and 2-arylidene-1,3-indanediones

The 1,3-dipolar cycloaddition of active azomethine ylide, which were generated in situ from addition reaction of α-amino acids with dialkyl acetylenedicarboxylates, with 2-arylidene-1,3-indanediones showed versatile regioselectivity and diastereoselectivity. The reaction of sarcosine and glycine afforded one kind of functionalized spiro[indene-2,3′-pyrrolidines]. The other primary α-amino acids such as alanine, phenylalanine and leucine gave another kind of regioisomeric spiro[indene-2,3′-pyrrolidines]. The cyclic α-amino acids resulted in the corresponding spiro[indene-2,2′-pyrrolizines] and [indene-2,6’-pyrrolo[1,2-c]thiazoles].

Peptidyl-Prolyl Model Study: How Does the Electronic Effect Influence the Amide Bond Conformation?

The triple-helical structure of collagen, the most abundant protein in animal bodies, owes its stability to post-translationally installed hydroxyl groups at position 4 of prolyl residues. To shed light on the nature of this phenomenon, we have examined the influence of the 4-substituent on the amide isomerism in peptidyl-prolyl analogues. The rigid bicyclic skeleton of 2,4-methanoprolines allowed us to follow the through-bond impact of the substituent group (electronic effect) without the side-chain conformation being affected by a stereoelectronic effect. These proline analogues were prepared by [2 + 2] photocycloaddition of (2-allylamino)acrylic acid derivatives. Subsequent pKa studies demonstrated a remarkable electronic effect of the 4-fluorine substitution, while the effect of the 4-methyl group was negligible. The trans/cis amide ratio was measured in model compounds under low temperature conditions. The observed prevalence for a trans-amide is extraordinary, and in this regard, 2,4-methanoproline is closer to primary α-amino acids than to proline. At the same time the amide rotation velocities were 3-4 orders of magnitude higher when compared to N-acetylprolyl. Finally, our results indicate that the electronic effect of the 4-substituent only affects the kinetics of the amide isomerization but not the thermodynamic prevalence for the trans-rotamer.

Molecular diversity of the three-component reaction of α-amino acids, dialkyl acetylenedicarboxylates and N-substituted maleimides

The one-pot three-component reaction of secondary α-amino acids, including proline, thiazolidine-4-carboxylic acid, and piperidine-2-carboxylic acid sarcosine with dialkyl acetylenedicarboxylate and N-substituted maleimides in refluxing ethanol afforded functionalized pyrrolo[3,4-a]pyrrolizines, pyrrolo[3',4':3,4]pyrrolo[1,2-c]thiazoles, pyrrolo[3,4-a]indolizines and octahydropyrrolo[3,4-c]pyrroles in good yields and with high diastereoselectivity. On the other hand, the similar three-component reaction containing primary α-amino acids, such as glycine, alanine, phenylalanine and leucine, with N-substituted maleimides and two molecules of dialkyl acetylenedicarboxylate obtained the corresponding hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)maleates.

Enantioselective aldol reaction between isatins and cyclohexanone catalyzed by amino acid sulphonamides.

Sulphonamides derived from primary α-amino acid were successfully applied to catalyze the aldol reaction between isatin and cyclohexanone under neat conditions. More interestingly, molecular sieves, as privileged additives, were found to play a vital role in achieving high enantioselectivity. Consequently, high yields (up to 99%) along with good enantioselectivities (up to 92% ee) and diastereoselectivities (up to 95:5 dr) were obtained. In addition, this reaction was also conveniently scaled up, demonstrating the applicability of this protocol.

Convenient synthesis of functionalized spiro[indoline-3,2'-pyrrolizines] or spiro[indoline-3,3'-pyrrolidines] via multicomponent reactions.

A general and practical route for the in situ generation of a new type of azomethine ylide and its sequential 1,3-dipolar cycloaddition reaction was successfully established. The three-component reaction of secondary α-amino acids including proline, sarcosine, thiazolidine-4-carboxylic acid with dialkyl acetylenedicarboxylate and 3-methyleneoxindoles in refluxing ethanol afforded the functionalized spiro[indoline-3,2'-pyrrolizines], spiro[indoline-3,3'-pyrrolidines] and spiro[indoline-3,6'-pyrrolo[1,2-c]thiazoles] in good yields and with high diastereoselectivity. Furthermore, similar multicomponent reactions using primary α-amino acids such as glycine, alanine and phenylalanine resulted in the corresponding (spiro[indoline-3,3'-pyrrolidine]-1'-yl)maleates.

ChemInform Abstract: Asymmetric α‐Allylation of α‐Branched Aldehydes with Allyl Alcohols by Synergistic Catalysis Using an Achiral Palladium Complex and a Chiral Primary Amino Acid.

Highly enantioselective direct α-allylation of α-branched aldehydes with simple allyl alcohols was achieved by the combined use of an achiral transition-metal catalysis with a palladium complex and a chiral organocatalysis with a readily obtainable primary α-amino acid. Various α-allylated aldehydes possessing a stereocontrolled quaternary carbon stereogenic center were synthesized in high yields with high enantioselectivity.

Zwitterionic chiral stationary phases based on cinchona and chiral sulfonic acids for the direct stereoselective separation of amino acids and other amphoteric compounds

An extensive series of free amino acids and analogs were directly resolved into enantiomers (and stereoisomers where appropriate) by HPLC on zwitterionic chiral stationary phases (Chiralpak ZWIX(+) and Chiralpak ZWIX(-)). The interaction and chiral recognition mechanisms were based on the synergistic double ion-paring process between the analyte and the chiral selectors. The chiral separation and elution order were found to be predictable for primary α-amino acids with apolar aliphatic side chains. A systematic investigation was undertaken to gain an insight into the influence of the structural features on the enantiorecognition. The presence of polar and/or aromatic groups in the analyte structure is believed to tune the double ion-paring equilibrium by the involvement of the secondary interaction forces such as hydrogen bonding, Van der Waals forces and π-π stacking in concert with steric parameters. The ZWIX chiral columns were able to separate enantiomers and stereoisomers of various amphoteric compounds with no need for precolumn derivatization. Column switching between ZWIX(+) and ZWIX(-) is believed to be an instrumental tool to reverse or control the enantiomers elution order, due to the complementarity of the applied chiral selectors.

Asymmetric α-Allylation of α-Branched Aldehydes with Allyl Alcohols by Synergistic Catalysis Using an Achiral Palladium Complex and a Chiral Primary Amino Acid

Highly enantioselective direct α-allylation of α-branched aldehydes with simple allyl alcohols was achieved by the combined use of an achiral transition-metal catalysis with a palladium complex and a chiral organocatalysis with a readily obtainable primary α-amino acid. Various α-allylated aldehydes possessing a stereocontrolled quaternary carbon stereogenic center were synthesized in high yields with high enantioselectivity.

Direct Asymmetric α-Allylation of α-Branched Aldehydes by Two Catalytic Systems with an Achiral Pd Complex and a Chiral Primary α-Amino Acid

Direct α-allylation of α-branched aldehydes was successfully carried out with a readily available allyl ester by combined use of two catalytic systems: Tsuji-Trost allylation reaction with an achiral palladium complex and enamine catalysis with a chiral primary α-amino acid. A quaternary carbon stereogenic center was constructed stereoselectively to give various 2,2-disubstituted pent-4-enals in good yields with high enantioselectivity.

Metal-free synthesis of polysubstituted oxazoles via a decarboxylative cyclization from primary α-amino acids

Abstract Background The ubiquitous oxazoles have attracted more and more attention in both industrial and academic fields for decades. This interest arises from the fact that a variety of natural and synthetic compounds which contain the oxazole substructure exhibit significant biological activities and antiviral properties. Although various synthetic methodologies for synthesis of oxazols have been reported, the development of milder and more general procedure to access oxazoles is still desirable. Results In this manuscript, a novel method for synthesis of polysubstituted oxazoles was developed from metal-free decarboxylative cyclization of easily available primary α-amino acids with 2-bromoacetophenones. Conclusions The method was simple, and this reaction could be carried out smoothly under mild and metal-free conditions. By virtue of this method, various polysubstituted oxazoles were obtained from the primary α-amino acids with moderate yields.

Direct construction of novel exo′-selective spiropyrrolidine bisoxindoles via a three-component 1,3-dipolar cycloaddition reaction

An efficient synthesis of novel exo′-selective spiropyrrolidine bisoxindoles has been achieved via a three-component 1,3-dipolar cycloaddition reaction. The azomethine ylides generated in situ from substituted isatin and primary α-amino acid methyl ester (or primary α-amino acids) reacted with the Knoevenagel adducts of substituted isatin to furnish novel spiropyrrolidine bisoxindoles in high yields (up to 99%). The structure and relative stereochemistry of cycloadducts were confirmed by single crystal X-ray diffraction. The possible mechanism was proposed and the cycloaddition proceeded via exo′-transition state.

Synthesis and antibacterial properties of new N4-acetylated hexahydro-2,7-dioxopyrido[2,3-f]quinoxaline-8-carboxylic acids

Direct interaction between 7-chloro-1-cyclopropyl-6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid and primary α-amino acids (exemplified by glycine, alanine, and l-valine) in aqueous ethanolic NaHCO3 at 70–80°C for 24–72 h produced the respective N-(4-oxoquinolin-7-yl)-α-amino acids (6a–c). The latter derivatives underwent reductive lactamization upon treatment with Na2S2O4 in aqueous ethanol to afford moderate yields of the corresponding pyrido[2,3-f]quinoxaline-8-carboxylic acids (8a–c). Acetylation of 8a–c using acetyl chloride afforded N4-acetylated hexahydro-2,7-dioxopyrido[2,3-f]quinoxaline-8-carboxylic acids (9a–c). The structures, assigned to these new heterocyclic products, are supported by analytical and spectral data. The synthesized compounds (6a–c/9a–c) showed appreciable antibacterial activity as compared with ciprofloxacin.

Metal-free intramolecular oxidative decarboxylative amination of primary α-amino acids with product selectivity

A novel metal-free intramolecular oxidative decarboxylative coupling of primary α-amino acids with 2-aminobenzoketones under mild and neutral conditions was developed. Different quinazolines can be selectively obtained by various oxidants.

Kinetics and Mechanism of the Permanganate-Induced Oxidative Catalytic Condensation of Sarcosine to a Diketopiperazine

The kinetics and mechanism of the permanganate-induced oxidative catalytic condensation reaction of sarcosine, as a secondary amino acid, in buffered medium (pH = 1-3) has been investigated spectrophotometrically. Analysis of the reaction products has shown that, in contrast to oxidation product of primary α-amino acids which is an aldehyde species, a valuable diketopiperazine compound namely 1,4-dimethylpiperazine-2,5-dione has been obtained as the sole product in 95% yield via a cheap, simple, efficient, and novel method. In an analogy to some α-amino acids in concentrated acidic medium, conclusive evidence has demonstrated delayed autocatalytic activity by Mn2+ in this reaction. It has been found that such activity can appear when a certain concentration ratio of Mn2+ to sarcosine is built up in the medium, which we call the “critical ratio”. Decisive results have shown that the magnitude of the latter ratio depends on pH, and the exhibition of autocatalytic activity is affected by the pH and ionic strength of the medium. Regarding the “delayed autocatalytic behaviour” of Mn2+ ions, rate equations have been presented confirming observations for both catalytic and non-catalytic routes. The reaction displays a first order dependence on permanganate ions and sarcosine concentrations, both in the catalytic and non-catalytic pathways, and an apparent first order dependence on Mn2+ ions in the catalytic pathway. The “critical ratio” and “delayed autocatalytic behaviour” concepts have been corroborated by the correspondence of the pseudo-order rate constants of the catalytic and non-catalytic pathways to the Arrhenius and Eyring laws. The activation parameters associated with both pathways have been calculated and discussed. The much higher value of the activation entropy obtained for the catalytic process sows that this factor controls the higher reaction rate relative to that of the non-catalytic pathway. Mechanisms for both catalytic and non-catalytic routes have been proposed which include formation of a bislactam product through a diacylperoxide intermediate.

Formation of Isoleucine-Specific Maillard Products from [1-13C]-D-Glucose and [1-13C]-D-Fructose

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFormation of Isoleucine-Specific Maillard Products from [1-13C]-D-Glucose and [1-13C]-D-FructoseRoland Tressl, Christiane Nittka, Evelyn Kersten, and Dieter RewickiCite this: J. Agric. Food Chem. 1995, 43, 5, 1163–1169Publication Date (Print):May 1, 1995Publication History Published online1 May 2002Published inissue 1 May 1995https://doi.org/10.1021/jf00053a009RIGHTS & PERMISSIONSArticle Views617Altmetric-Citations65LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (811 KB) Get e-Alerts Get e-Alerts

XY–ZH systems as potential 1,3-dipoles. Part 11. Stereochemistry of 1,3-dipoles generated by the decarboxylative route to azomethine ylides

The decarboxylative reaction of aryl aldehydes with cyclic secondary α-amino acids or primary α-amino acids in the presence of N-methyl- or N-phenyl-maleimide leads, via an intermediate azomethine ylide, to mixtures of bicyclic pyrrolidine cycloadducts in good yield. Cyclic secondary α-amino acids, where the carboxylic group is non-benzylic, give cycloadducts arising from a stereospecifically generated anti-dipole. Acyclic α-amino acids, and cyclic secondary α-amino acids with the carboxylic group located at a benzylic site, give rise to cycloadducts derived from both anti- and syn-configurations of the intermediate azomethine glides. The reactions show little discrimination between endo- and exo-transition states for the cycloadditions.

XY–ZH systems as potential 1,3-dipoles. Part 12. Mechanism of formation of azomethine ylides via the decarboxylative route from α-amino acids

The effect of temperature, solvent, and type of aldehyde on the stereospecific or stereoselective formation of azomethine ylides by the decarboxylative condensation of aldehydes with three types of α-amino acids, (i) cyclic secondary α-amino acids, (ii) cyclic secondary α-amino acids with a benzylic carboxy group, and (iii) acyclic primary α-amino acids, has been studied. Stereospecific anti-dipole formation in (i) and temperature dependent stereoselective anti-dipole formation in (ii) and (iii) is inferred from the stereochemistry of cycloadducts of the azomethine ylides with N-methylmaleimide. These results are used to support a mechanistic scheme involving loss of carbon dioxide from intermediate oxazolidin-5-ones in a stereospecific cycloreversion reaction.

Equilibrium and hydrolysis of ?-amino acid esters in mixed-ligand complexes with diethylenetriaminepalladium(II)

The mixed-ligand complexes of palladium(II) containing diethylenetriamine as a primary ligand and α-amino acid esters as secondary ligands were studied using potentiometric and conductometric techniques. The equilibrium and/or stability constants of the binary and mixed-ligand complexes formed were determined. The kinetics of base hydrolysis of the above esters in the presence and absence of PdII-dien complexes were studied at 30°C. The rate and catalysis constants were determined.