Dithio and thiono. Esters. 61. Synthesis of α-Amino Dithioesters and Endothiodipeptides

The α-amino ester hydrochlorides ( 1 ) are converted into N-protected α-amino amides ( 3 ), α-amino thioamides ( 4 ) and α-amino dithiomethylesters ( 5 ). Condensation of 5 with the alkali salts of α-amino acids gives rise to the endothiodipeptide alkali salts ( 7 ).     

Application of nickel(II) complexes to the efficient synthesis of α- or β-amino acids

Nonproteinogenic α- or β-amino acids have attracted tremendous attention, as they are widely utilized for biological, biochemical, pharmaceutical, and asymmetric chemical investigations. Recently, we developed a series of new strategies for preparing achiral and chiral nickel(ii) complexes for the synthesis of amino acids. We applied these new methods utilizing chiral nickel(ii) complexes for the asymmetric Mannich reaction to synthesize enantiopure α,β-diamino acids, the enantioselective tandem conjugate addition-elimination reaction to prepare glutamic acid derivatives, the Suzuki coupling reaction to yield β(2)-amino acid derivatives, the asymmetric Mannich reaction to synthesize 3-aminoaspartate, the asymmetric Michael addition reaction to give β-substituted-α,γ-diaminobutyric acid derivatives, the asymmetric alkylation reaction to prepare linear ω-trifluoromethyl containing amino acids, and the asymmetric Michael addition reaction to synthesize syn-β-substituted tryptophans.     

Introduction of two polyvinyl alcohol resins for efficient solid support Cu-catalyzed N-arylation of α-aminoacids with aryl halides in aqueous media

In this article, two polyvinyl alcohol (PVA)-based resins were prepared by crosslinking of epoxidized PVA-chains using of 4-(4-aminobenzyl)benzenamine as a crosslinker and polymerization of acrylated PVA chains in the another approach. The prepared PVA resins showed well hydrophilic and swelling properties in various organic solvents, which are used in solid-phase organic synthesis (SPOS). Swelling properties of these resins were examined in dimethylformamide, tetrahydrofuran, water, ethanol, methanol, dichloromethane, and dioxane. Furthermore, the both resins were characterized by FTIR and ¹H-NMR and their properties such as epoxy equivalent weight (EEW) of epoxidized PVA and density of the resins were determined by analytical methods. Then, α-amino acids such as L-aspartic acid, L-leucine, L-alanine, L-serine, L-valine, L-threonine, and L-tyrosine were immobilized on both resins through esterification reaction between these α-amino acids with the present hydroxyl groups on PVA resines, to carry out their solid-phase N-arylation reaction in the presence of CuI as a catalyst in milder and greener conditions than free resin protocols. Hydrolysis of the correponding N-arylated α-amino acids immobilized on the resins gave the N-arylated α-amino acids in high to excellent yields. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47597.     

Synthesis of copper(II) complexes of asymmetric resins prepared by attachment of α-amino acids to crosslinked polystyrene

In order to use ligand exchange resins for chromatographic resolution of racemic compounds, two series of asymmetric sorbents were prepared by attachment of various optically active α-amino acids onto crosslinked polystyrene. Chloromethylated and chlorosulfonated styrene–divinylbenzene copolymers were prepared and then treated with α-amino acids. Results show that reaction of α-amino acids with polystyrene could be carried to a substitution of 15% to 40% of the aromatic rings depending on many parameters. Stable copper(II) complexes of the asymmetric resins were prepared. Potentiometric methods were adapted to the case of insoluble materials such as resins. These methods indicate that bis-chelate complexes are formed.     

1-氨基-1-环烷基甲酸的合成

通过改进的Strecker法,分别以环己酮和环戊酮为原料与氨反应生成亚胺（I）,（I）与氰化钠反应生成（Ⅱ）,（Ⅱ）用浓盐酸水解为旷氨基酸（Ⅲ）。反应最佳条件为：环烷基酮、氨水、氯化铵和氰化钠的摩尔比为：1：1．8：1．1：1．1。粗品旷氨基酸用75％的乙醇重结晶。1-氨基-1-环己基甲酸和1-氨基-1-环戊基甲酸的收率分别为56．42％和60．21％。目标化合物用核磁和红外光谱进行了表征。     

Self-disproportionation of Enantiomers (SDE) of Chiral Nonracemic Amides via Achiral Chromatography

This article is based on a review of literature devoted to the phenomenon of SDE via achiral chromatography since the appearance of the seminal work of Professor Emanuel Gil-Av. The discussed examples of chromatographic studies are related to amides derived from chiral amines and α- and β-amino acids. We discuss the observed SDE magnitude as a function of a compound's structure, and composition of eluent and stationary phases, providing some mechanistic considerations. Particular emphasis is given to the aspect of SDE via achiral chromatography as an emerging unconventional enantiomeric purification technique.     

High Surface Area MgO as a Highly Effective Heterogeneous Base Catalyst for Three-Component Synthesis of Tetrahydrobenzopyran and 3,4-Dihydropyrano[c]chromene Derivatives in Aqueous Media

Magnesium oxide (MgO) as a highly effective heterogeneous base catalyst effectively catalyzes the three component reaction of aryl aldehydes, malononitrile and α-hydroxy or α-amino activated C–H acids such as 1,3-cyclohexanedione, dimedone, 4-hydroxy-6-methylpyrone, 4-hydroxycoumarin, 1,3-dimethylbarbituric acid and 1,3-dimethyl-6-amino uracil to the formation of the corresponding pyran annulated heterocyclic systems. The catalyst is inexpensive and easily obtained, stable and storable, easily recycled and reused for several cycles with consistent activity.     

Reactions with 2-thiazolin-5-ones. III. The behaviour of 4-Arylazo-2-alkoxy-2-thiazolin-5-ones toward amines and Grignard reagents

Treatment of 4-arylazo-2-alkoxy-2-thiazolin-5-ones 4a – f with glycine or phenylhydrazine effects their conversion into 1-aryl-5-alkoxy-1 H-1,2,4-triazole-3-carboxylic acid derivatives 5a – j , with the loss of hydrogen sulfide. On the other hand, the reaction of the 2-ethoxy ( 4a – c ) and the 2-isopropyloxy ( 4g – i ) derivatives with strong basic amines involves the loss of an alkyl mercaptan to yield the N-substituted amines 7d – j of 1-aryl-Δ²-1,2,4-triazolin-5-one-3-carboxylic acids. The 2-benzyloxy derivatives 4d – f react with the same reagents to give the N-substituted amides 2a – g of 1-aryl-Δ²-1,2,4-triazolin-5-thione-3-carboxylic acids, with the loss of benzyl alcohol. Hetero-ring opening of 4 , followed by recyclisation, occurs upon treatment with ethyl or phenyl magnesium halides to yield the triazolinethione derivatives 13 a – c .     

Linoleic Acid Oxidation Catalysed by Various Amino Acids and Cupric Ions in Non-Aqueous Media

The effect of amino acids under the present investigation on linoleic acid oxidation in non-aqueous media has shown feature of an autocatalytic chain reaction and possessed minor antioxidant behaviour except cysteine. The antioxidant effect might be attributed to the absence of protonated amino nitrogen. Linoleic acid alone had an induction period of 15 hr and on the addition of various α-amino acids, the systems had an induction period ranged from 16–19 hr. This increase did not exhibit any specific function for the studied amino acids. Cysteine exceptionally possessed pro-oxidant effect and that was due to the role of HS-group. The addition of copper at concentrations of 10^?5 M and 10^?3 M to the model systems composed of linoleic acid and various α-amino acids in non-aqueous media have shown to exhibit minor and highly pro-oxidant effects respectively. The pro-oxidant effect of these amino acids in the presence of copper might be due to amino acids-copper complexes.     

手性α-氨基酸的不对称合成

按合成方法综述了手性α-氨基酸的研究进展。简要介绍了手性拆分、L-氨基酸的高同系化、不对称烷基化、亚胺的不对称烷基化、脱氢氨基酸的不对称氢化等各种合成方法。对手性α-氨基酸合成的今后发展方向做了讨论。     

Scalable and Selective β-Hydroxy-α-Amino Acid Synthesis Catalyzed by Promiscuous l-Threonine Transaldolase ObiH

Enzymes from secondary metabolic pathways possess broad potential for the selective synthesis of complex bioactive molecules. However, the practical application of these enzymes for organic synthesis is dependent on the development of efficient, economical, operationally simple, and well-characterized systems for preparative scale reactions. We sought to bridge this knowledge gap for the selective biocatalytic synthesis of β-hydroxy-α-amino acids, which are important synthetic building blocks. To achieve this goal, we demonstrated the ability of ObiH, an l -threonine transaldolase, to achieve selective milligram-scale synthesis of a diverse array of non-standard amino acids (nsAAs) using a scalable whole cell platform. We show how the initial selectivity of the catalyst is high and how the diastereomeric ratio of products decreases at high conversion due to product re-entry into the catalytic cycle. ObiH-catalyzed reactions with a variety of aromatic, aliphatic and heterocyclic aldehydes selectively generated a panel of β-hydroxy-α-amino acids possessing broad functional-group diversity. Furthermore, we demonstrated that ObiH-generated β-hydroxy-α-amino acids could be modified through additional transformations to access important motifs, such as β-chloro-α-amino acids and substituted α-keto acids.     

Helical Antimicrobial Peptide Foldamers Containing Non-proteinogenic Amino Acids

Antimicrobial peptides (AMPs) are potential novel therapeutic drugs against microbial infections. Most AMPs function by disrupting microbial membranes because of their amphipathic properties and ordered secondary structures. In this minireview, we describe recent efforts to develop helical AMP foldamers containing non-proteinogenic amino acids, such as α,α-disubstituted α-amino acids, β-amino acids, γ-amino acids, side-chain stapling and N-alkyl glycines.     

N-酰化-α-氨基酸金属配合物的研究进展

N-酰化-α-氨基酸作为氨基酸的一类衍生物,在参与生命活动过程中都显示出重要的作用。因此研究它们与金属元素的配位行为不仅是对金属氨基酸配合物体系的进一步完善和发展,同时也对认识金属离子的生物效应和作用机理有重要意义。     

Optical Resolution of α-Amino Acids by Reverse Osmosis using Enantioselective Polymer Membrane Containing Chiral Metal-Schiff Base Complex

The optical resolution of α-amino acids, arginine and alanine was performed by reverse osmosis at 517.10 kPa and 1034.21 kPa pressures using enantioselective composite nanofiltration membrane prepared by interfacial co-polymerizing, a mixture of Zinc metal Schiff's base complex and piperazine with trimesoyl chloride in-situ on the top of polysulfone ultrafiltration membrane. The chemical composition of the enantioselective layer was determined by ATR-FTIR and X-ray Fluorescence Spectroscopy and surface morphology was studied by scanning electron microscopy. The effect of process parameters such as the operating pressure, permeation time, and concentration of the feed on the performance of membrane was studied. The volumetric flux of aqueous solution of α-amino acids through membrane follows Hegen-Poiseuillie equation. The composite membrane permeates d-enantiomers of α-amino acids preferentially; 54% enantiomeric excess in for d-arginine was achieved. The enantioselective permeability of the membrane is found to be time dependent. The enantioselective property of the membrane has arisen due to a homo-Chiral environment created in the membrane by incorporating chiral ligand Schiff complex in thin film of poly (piperazine trimesamide) polymer on the top of the polysulfone membrane. The composite membrane also exhibits the separation of α-amino acids from their aqueous solutions.     

Amino-acids in humic,nitrohumic and nitrofuvic acids from coal

The humic acids, HA, extracted from a Spanish lignite and the nitrohumic acids, NHA, and nitrofulvic acids, NFA, extracted from the same lignite after its nitration, are hydrolysed with 6N HCI under reflux. The α-amino acids present in the hydrolysates are determined and thirteen α-amino acids are identified. The amounts of nitrogen in the amino-acids released by the hydrolysis increase according to the sequence: NFA > NHA > HA.     

Linoleic Acid Oxidation Catalysed by Various Amino Acids and Cupric Ions in Aqueous Media

Model systems were designed to study the linoleic acid oxidation in the presence and absence of various amino acids and with or without cupric ions. The tested amino acids have shown to possess potential pro-oxidant capacity in linoleic acid dispersed in aqueous media. The effectiveness of various amino acids on linoleic acid oxidation decreased in the following order: cysteine > serine > tryptophan > phenylalanine > histidine > alanine. The addition of alanine, serine, phenylalanine, histidine or tryptophan to linoleic acid have shown features of an autocatalytic oxidation chain reaction. With cysteine, there was a linear relation between concentration of hydroperoxides and time during the early stages of oxidation. The pro-oxidative activity of the tested amino acids in general could be attributed to the presence of the α-amino group in the form H₃-N-R. The apparent difference in the pro-oxidative activity is mainly due to the functional groups attached to β-carbon in the amino acid molecules. The addition of cupric ions at concentration of 10^–5 M to linoleic acid catalysed with various α-amino acids have shown that these amino acids had no significant effect. The increasing copper concentration from 10^–5 to 10^–1 M shortened the induction period of linoleic acid catalysed by amino acids having aromatic side chain, had no effect on the induction period but increased the oxidation rate during the propagation step in the model systems catalysed by alanine and serine and in the model system containing cysteine increased the linoleic acid oxidation linearly from the start of the reaction.     

DPP-4 Cleaves α/β-Peptide Bonds: Substrate Specificity and Half-Lives

The incorporation of β-amino acids into a peptide sequence has gained particular attention as β- and α/β-peptides have shown remarkable proteolytic stability, even after a single homologation at the scissile bond. Several peptidases have been shown to cleave such bonds with high specificity but at a much slower rate compared to α-peptide bonds. In this study, a series of analogs of dipeptidyl peptidase-4 (DPP-4) substrate inhibitors were synthesized in order to investigate whether β-amino acid homologation at the scissile bond could be a valid approach to improving peptide stability towards DPP-4 degradation. DPP-4 cleaved the α/β-peptide bond after the N-terminal penultimate Pro with a broad specificity and retained full activity regardless of the β³-amino acid side chain and peptide length. Significantly improved half-lives were observed for β³Ile-containing peptides. Replacing the penultimate Pro with a conformationally constrained Pro mimetic led to proteolytic resistance. DPP-4 cleavage of α/β-peptide bonds with a broad promiscuity represents a new insight into the stability of peptide analogs containing β-amino acids as such analogs were thought to be stable towards enzymatic degradation.     

Some 9-Amino-Acridine Derivatives Containing Silicon

p-Tri-methylsilylphenethylamine and 1-p-trimethylsilyphenyl-1-amino-4-dimethylamino-butane were reacted with 9-chloroacridines to give the corresponding N-substituted 9-amino acridines, which inhibited the growth of several bacteria but not yeasts.     

Analytik und Biophysik von verzweigtkettigen Fettsäuren in Lipiden

Analytics and biophysics of branched fatty acids in lipids . Objects of our investigations are long chain fatty acids with methyl groups in different positions and fatty acids with a different length of the sidegroup in α-position. The separation of racemic branched fatty acid methyl esters by gas chromatography on a chiral column depends on the structure of the branched fatty acid. Diastereomeric amides and phosphatidylcholines with α-branched fatty acid residues were separated preparatively. The branched fatty acids were incorporated into 1,2-diacyl-, 1-acyl-2-hexadecyl- and 2-acyl-1-hexadecyl-glycerophosphocholines and characterized by differential scanning calorimetry and X-ray diffraction.     

Ceramides from the spongeDysidea etheria

Ceramides have been isolated from the polar organic extracts of the spongeDysidea etheria. The ceramides proved to be amides of sphingosine with either normal, saturated fatty acids or saturated α-hydroxy fatty acids. Sphingosine was identified by isolation from the hydrolysis reaction mixture, acetylation and comparison of its physical and spectral properties with those reported for authentic sphingosine triacetate. The acids were identified by gas chromatography-mass spectrometry analysis of their respective methyl esters.