Glycine Derivatives Research Articles

Identification of acetolactate synthase resistant Amaranthus retroflexus in Ukraine

The problem of weed resistance to herbicides has become very important in the last decade and threatens to dramatically reduce the productivity and profitability of modern crop production. Herbicides – ALS inhibitors dominate among current herbicides and are used annually on large areas of sunflower, wheat, corn, soybean, and rapeseed. Also, in recent years, Clearfield seeds of sunflower, corn, canola, soybean and wheat have been sown in large areas. In recent years, there has been a sharp decrease in Amaranthus retroflexus L. control levels by imidazolinone class herbicides. Thus, the effects of herbicides with different modes of action on the development of A. retroflexus on sunflower after imidazolinone application were investigated in field research. In the conditions of the Cherkasy region of Ukraine, the biotype A. retroflexus was identified, which is resistant to the post-emergence application of herbicides - acetolactate synthase (ALS) inhibitors of the imidazolinone class – imazapyr and imazamox. Weed plants treated with imidazolinone derivatives in the maximum doses registered in Ukraine did not differ from untreated control plants. Also, in the conditions of field experiments, cross resistance of the weed biotype to herbicides – ALS inhibitors of the sulfonylurea class – foramsulfuron and iodosulfuron-methyl-sodium, thifensulfuron-methyl, tribenuron-methyl, nicosulfuron was established; and also, to the triazolinone derivative – thiencarbazone-methyl; to triazolpyrimidine derivatives – florasulam and flumetsulam. Multiple resistance of the A. retroflexus biotype to herbicides of the classes of glycine derivatives – glyphosate, phenoxycarboxylates – 2,4-D, benzoic acid – dicamba has not been established; compositions of dicamba with triketone – topramesone; diphenyl ethers – aclonifen; pyridine carboxylates – clopyralid, picloram and aminopyralid. It was shown for the first time that herbicide compositions with selected nutrients (ammonium pool) can increase the level of effectiveness of controlling resistant weed biotypes. Thus, the addition of ammonium sulfate increases the effectiveness of controlling ALS-resistant A. retroflexus with herbicides – a derivative of benzoic acid (dianate) and a derivative of benzoic acid with a 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor (stellar – dicamba + topramesone). Thus, the A. retroflexus biotype resistant to ALS-herbicides of the imidazolinone class was identified for the first time in Ukraine, which is cross-resistant to other ALS-inhibitors of the sulfonylureas, triazolinones, and triazolpyrimidine classes. Multiple resistance of A. retroflexus to herbicides of the classes of glycine derivatives – glyphosate; phenoxycarboxylates – 2,4-D; benzoic acid – dicamba, triketones – topramesone; diphenyl ethers – aclonifen; pyridine carboxylates – clopyralid, picloram and aminopyralid has not been established. The identification of a highly harmful weed species resistant to widely used herbicides – ALS inhibitors in the central part of the "grain belt" of Ukraine requires a significant revision of the principles of crop rotation formation and ways of controlling weeds in the country in order to maintain high levels of profitability and productivity of agrophytocenoses.

Antamanide Analogs as Potential Inhibitors of Tyrosinase.

The tyrosinase enzyme, which catalyzes the hydroxylation of monophenols and the oxidation of o-diphenols, is typically involved in the synthesis of the dark product melanin starting from the amino acid tyrosine. Contributing to the browning of plant and fruit tissues and to the hyperpigmentation of the skin, leading to melasma or age spots, the research of possible tyrosinase inhibitors has attracted much interest in agri-food, cosmetic, and medicinal industries. In this study, we analyzed the capability of antamanide, a mushroom bioactive cyclic decapeptide, and some of its glycine derivatives, compared to that of pseudostellarin A, a known tyrosinase inhibitor, to hinder tyrosinase activity by using a spectrophotometric method. Additionally, computational docking studies were performed in order to elucidate the interactions occurring with the tyrosinase catalytic site. Our results show that antamanide did not exert any inhibitory activity. On the contrary, the three glycine derivatives AG9, AG6, and AOG9, which differ from each other by the position of a glycine that substitutes phenylalanine in the parent molecule, improving water solubility and flexibility, showed tyrosinase inhibition by spectrophotometric assays. Analytical data were confirmed by computational studies.

Photoredox Cross-Dehydrogenative Coupling of N-Aryl Glycines Mediated by Mesoporous Graphitic Carbon Nitride: An Environmentally Friendly Approach to the Synthesis of Non-Proteinogenic α-Amino Acids (NPAAs) Decorated with Indoles.

Indole-decorated glycine derivatives are prepared through an environmentally benign cross-dehydrogenative coupling between N-aryl glycine analogues and indoles (yield of ≤81%). Merging heterogeneous organocatalysis and photocatalysis, C–H functionalization has been achieved by selective C-2 oxidation of N-aryl glycines to afford the electrophilic imine followed by Friedel–Crafts alkylation with indole. The sustainability of the process has been taken into account in the reaction design through the implementation of a metal-free recyclable heterogeneous photocatalyst and a green reaction medium. Scale-up of the benchmark reaction (gram scale, yield of 69%) and recycling experiments (over seven runs without a loss of efficiency) have been performed to prove the robustness of the protocol. Finally, mechanistic studies were conducted employing electron paramagnetic resonance spectroscopy to unveil the roles of the photocatalyst and oxygen in the formation of odd-electron species.

Combination of Glycinamide and Ascorbic Acid Synergistically Promotes Collagen Production and Wound Healing in Human Dermal Fibroblasts.

The purpose of this study is to present a novel strategy to enhance collagen production in cells. To identify amino acid analogs with excellent collagen production-enhancing effects, human dermal fibroblasts (HDFs) were treated with 20 kinds of amidated amino acids and 20 kinds of free amino acids, individually at 1 mM. The results showed that glycinamide enhanced collagen production (secreted collagen level) most effectively. Glycine also enhanced collagen production to a lesser degree. However, other glycine derivatives, such as N-acetyl glycine, N-acetyl glycinamide, glycine methyl ester, glycine ethyl ester, and glycyl glycine, did not show such effects. Glycinamide increased type I and III collagen protein levels without affecting COL1A1 and COL3A1 mRNA levels, whereas transforming growth factor-β1 (TGF-β1, 10 ng mL−1) increased both mRNA and protein levels of collagens. Ascorbic acid (AA, 1 mM) increased COL1A1 and COL3A1 mRNA and collagen I protein levels. Unlike TGF-β1, AA and glycinamide did not increase the protein level of α-smooth muscle actin, a marker of differentiation of fibroblasts into myofibroblasts. The combination of AA and glycinamide synergistically enhanced collagen production and wound closure in HDFs to a level similar to that in cells treated with TGF-β1. AA derivatives, such as magnesium ascorbyl 3-phosphate (MAP), 3-O-ethyl ascorbic acid, ascorbyl 2-O-glucoside, and ascorbyl tetraisopalmitate, enhanced collagen production, and the mRNA and protein levels of collagens at 1 mM, and their effects were further enhanced when co-treated with glycinamide. Among AA derivatives, MAP had a similar effect to AA in enhancing wound closure, and its effect was further enhanced by glycinamide. Other AA derivatives had different effects on wound closure. This study provides a new strategy to enhance cell collagen production and wound healing using glycinamide in combination with AA.

Investigation of the physico-chemical interaction of ct-DNA with Anticancer Glycine Derivative of Pt-complex by applying docking and MD simulation methods and multi-spectroscopic techniques

The interaction of tertpentyl glycine derivative of platinum complex with ct-DNA was studied by applying diverse spectroscopic methods (UV–vis and fluorescence quenching method, kinetic reaction, circular dichroism (CD), thermal denaturation); also, computational studies (including molecular docking and molecular dynamic (MD) simulation) were carried out in this research. The Stern-Volmer quenching constants for the Platinum complex were calculated, thus revealing that Pt-complex had interaction with ct-DNA the static fluorescence quenching. The results obtained by UV-Vis absorbance, circular dichroism and fluorescence techniques demonstrated that the glycine derivative of platinum complex in ct-DNA was induced by the binding of Platinum complex, thus leading to some changes in its structure. The kinetic parameters of the interaction were investigated as well, which displayed a second-order kinetic. The empirical results were obtained and compared with those achieved by the molecular docking and MD simulation. Further, the docking and molecular dynamics simulation results showed that the cisplatin-glycine derivative could have binding to ct-DNA, and hydrophobic interactions played a major role in stabilizing the complex. Therefore, the glycine derivative of the platinum complex can act as an anti-cancer agent.

Visible‐Light‐Promoted Stereoselective C(sp3)−H Glycosylation for the Synthesis of C‐Glycoamino Acids and C‐Glycopeptides

AbstractThe glycosylative modification of peptides could improve the pharmacological properties of peptide drugs and deliver them efficiently to the target sites. Compared with O‐/N‐glycosides, C‐glycosides exhibit more metabolic stability. We here disclose the first example of visible‐light‐promoted and Cu‐catalyzed stereoselective C‐glycosylation. The mild reaction conditions are compatible with various carbohydrate substrates, as demonstrated with a series of monosaccharides and a disaccharide, and are amenable to the synthesis of a wide variety of C‐glycoamino acids and C‐glycopeptidomimetics with good yields and excellent stereoselectivities. The dual‐functional photocatalyst formed in situ via coordination of the glycine derivative and the chiral phosphine Cu complex could not only catalyze the photoredox process but also control the stereoselectivity of the glycosylation reaction.

Visible-Light-Promoted Stereoselective C(sp3 )-H Glycosylation for the Synthesis of C-Glycoamino Acids and C-Glycopeptides.

The glycosylative modification of peptides could improve the pharmacological properties of peptide drugs and deliver them efficiently to the target sites. Compared with O-/N-glycosides, C-glycosides exhibit more metabolic stability. We here disclose the first example of visible-light-promoted and Cu-catalyzed stereoselective C-glycosylation. The mild reaction conditions are compatible with various carbohydrate substrates, as demonstrated with a series of monosaccharides and a disaccharide, and are amenable to the synthesis of a wide variety of C-glycoamino acids and C-glycopeptidomimetics with good yields and excellent stereoselectivities. The dual-functional photocatalyst formed in situ via coordination of the glycine derivative and the chiral phosphine Cu complex could not only catalyze the photoredox process but also control the stereoselectivity of the glycosylation reaction.

Bismuth-catalyzed arylation of ethyl glyoxylate with aniline via N-H insertion.

Glycine derivatives such as ethyl 2-(4-aminophenyl)-2-(phenylamino) acetate is an exciting and essential non-proteinogenic class of amino acids. Herein, we report an efficient and novel route to synthesize glycine derivatives using ethyl glyoxylate, aniline, and its derivatives catalyzed by bismuth salts. In our scheme, mild, non-toxic, and commercially viable reagents were utilized. The synthesized moieties were characterized by ESI-MASS, 1H-NMR, 13C-NMR, and XRD techniques. The target glycine derivatives were successfully obtained with a maximum yield of 87%. Moreover, the reaction is very green as water is the only byproduct.

Diarylation of N- and O-nucleophiles through a metal-free cascade reaction

Diarylation of N- and O-nucleophiles through a metal-free cascade reaction

Synthesis and Optimization of Nitroxide-Based Inhibitors of Ferroptotic Cell Death in Cancer Cells and Macrophages.

JP4-039 is an alkene peptide isostere that acts as a low-micromolar inhibitor of erastin- and RSL-3-induced ferroptotic cell death in the HT-1080 cell line. In this work, we have developed new synthetic strategies that allow access to analogues of this lead structure. Enantioselective vinylogous Mannich or cross-metathesis reactions were key to the preparation of a series of analogues that culminated in the preparation of the ca. 30-fold more potent analogue (S)-6c. Structure-activity relationship analyses used both HT-1080 cells and a luminescence-based ferroptosis assay in RAW 264.7 macrophages. In particular, α,α-disubstituted alkene peptide isosteres (Rα ≠ H) were found to exceed the potency of the corresponding glycine (Rα = H) derivatives.

Interaction of evaporated glycine and dipeptide derivatives of glycine with He2+ ions

In this paper we have studied a mechanism for radiation damage of gas phase molecules of glycine [Gly] and dipeptide derivatives of glycine, such as diglycine [Gly-Gly], cyclo(glycylglycyl) [cyclo(Gly-Gly)] and glycyl-leucine [Gly-Leu] by the impact of He2+ ions with energy Ep = 4 keV/u. Relative cross sections of different elementary processes occurring in single collisions between dipeptide derivatives of glycine and ions have been measured for the first time. The fragmentation channels of both singly and multiply charged molecular ions have been studied experimentally. It has been shown that in the process of Gly-Gly sublimation, cyclization in the crystalline sample takes place, which results in formation of cyclo(Gly-Gly). Using the DFT method, the geometry of molecules and singly charged ions of glycine dipeptide derivatives has been calculated, as well as energies of different experimentally observed fragmentation channels of these ions.

Visible Light-Driven C–H Ketoalkylation of Glycine Derivatives with Cycloalkyl Peroxides

Visible Light-Driven C–H Ketoalkylation of Glycine Derivatives with Cycloalkyl Peroxides

Glycine derivatives with closed carboxyl group as effective co-initiators for radical photopolymerization in the presence of camphorquinone

Glycine derivatives with closed carboxyl group as effective co-initiators for radical photopolymerization in the presence of camphorquinone

Two New Prenylated Glycine Derivatives from the Marine-Derived Fungus Fusarium sp. TW56-10.

Two new prenylated glycine derivatives N-({4-[(3-methylbut-2-en-1-yl)oxy]phenyl}acetyl)glycine (1) and methyl N-({4-[(3-methylbut-2-en-1-yl)oxy]phenyl}acetyl)glycinate (2), along with nine known compounds (3-11) were purified from the marine-derived fungus Fusarium sp. TW56-10. Their chemical structures were determined by spectroscopic evidence, including extensive nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) data, infrared radiation (IR) and Ultraviolet spectra (UV). Compound 4 (8-O-methylfusarubin) exhibited cytotoxic activity with IC50 value of 11.45 μM for A549 cells.

Cu-Catalyzed decarboxylative annulation of N-substituted glycines with 3-formylchromones: synthesis of functionalized chromeno[2,3-b]pyrrol-4(1H)-ones.

A novel protocol was developed for preparing functionalized chromeno[2,3-b]pyrrol-4(1H)-ones 3 (CMPOs) from 3-formylchromones with N-substituted glycine derivatives. The method entailed decarboxylative annulation of the acyl group of 3-formylchromones by simply heating a mixture of substrates 1-2 and toluene oxidized by 2-di-tert-butyl peroxide (DTBP) and catalyzed by CuBr. As a result, a series of CMPOs 3 were produced via a cascade reaction. This protocol can be used to synthesize functionalized CMPOs via combinatorial and parallel syntheses in a one-pot reaction rather than a tedious multi-step reaction.

Hyperpolarization of 15N in an amino acid derivative.

Hyperpolarization is a nuclear magnetic resonance (NMR) technique which can be used to significantly enhance the signal in NMR experiments. In recent years, the possibility to enhance the NMR signal of heteronuclei by the use of para-hydrogen induced polarization (PHIP) has gained attention, especially in the area of possible applications in magnetic resonance imaging (MRI). Herein we introduce a way to synthesize a fully deuterated, 15N labelled amino acid derivative and the possibility to polarize the 15N by means of hydrogenation with para-hydrogen to a polarization level of 0.18%. The longevity of the polarization with a longitudinal relaxation time of more than a minute can allow for the observation of dynamic processes and metabolic imaging in vivo. In addition, we observe the phenomenon of proton–deuterium exchange with a homogeneous catalyst leading to signal enhanced allyl moeities in the precursor.

Formation and evolution of C-C, C-O, C[double bond, length as m-dash]O and C-N bonds in chemical reactions of prebiotic interest.

A series of prebiotic chemical reactions yielding the precursor building blocks of amino acids, proteins and carbohydrates, starting solely from HCN and water is studied here. We closely follow the formation and evolution of the pivotal C-C, C-O, C[double bond, length as m-dash]O, and C-N bonds, which dictate the chemistry of the molecules of life. In many cases, formation of these bonds is set in motion by proton transfers in which individual water molecules act as catalysts so that water atoms end up in the products. Our results indicate that the prebiotic formation of carbon dioxide, formaldehyde, formic acid, formaldimine, glycolaldehyde, glycine, glycolonitrile, and oxazole derivatives, among others, are best described as highly nonsynchronous concerted single step processes. Nonetheless, for all reactions involving double proton transfer, the formation and breaking of O-H bonds around a particular O atom occur in a synchronous fashion, apparently independently from other primitive processes. For the most part, the first process to initiate seems to be the double proton transfer in the reactions where they are present, then bond breaking/formation around the reactive carbon in the carbonyl group and finally rupture of the C-N bonds in the appropriate cases, which are the most reluctant to break. Remarkably, within the limitations of our non-dynamical computational model, the wide ranges of temperature and pressure in which these reactions occur, downplay the problematic determination of the exact constraints on the early Earth.

Catalyst-free visible light-induced decarboxylative amination of glycine derivatives with azo compounds

A visible light-induced, catalyst-free decarboxylative amination of glycine derivatives with azo compounds was achieved to deliver functionalized aminals under mild reaction conditions.

Thermo-induced decarboxylative α-C(sp3)–H fluoroalkylation of glycine derivatives with fluorinated peroxy esters

A thermo-induced α-C(sp3)–H fluoroalkylation of glycine derivatives with a new type of fluorinated peroxy ester is described.

Copper(I)-Catalyzed Asymmetric Synthesis of Unnatural α-Amino Acid Derivatives and Related Peptides Containing γ-(aza)Aryls

Chiral α-amino acids are indispensable compounds in organic chemistry, biochemistry, and medicinal chemistry. Herein, by means of copper(I)-catalyzed asymmetric conjugate addition of derivatives of glycine, serine, cysteine, and β-amino-alanine to electron-deficient vinyl(aza)arenes, an array of novel unnatural chiral α-amino acid derivatives bearing a γ-(aza)aryl is prepared in moderate to high yields with high enantioselectivity. Various azaarenes, such as pyrimidine, 1,3,5-triazine, pyridine, pyridine-N-oxide, quinoline, quinoxaline, purine, benzo[d]imidazole, benzothiazole, and 1,2,4-oxadiazole, are well tolerated. Moreover, the electrophiles are nicely extended to (Z)/(E) mixtures of electron-deficient butadienylpyridine and benzene, which are transformed to the corresponding chiral α-amino acid derivatives in high (E)/(Z) ratio and high enantioselectivity. More importantly, the present methodology is successfully applied in the catalytic asymmetric functionalization of Schiff bases derived from peptides, which finally afforded a new chiral tripeptide bearing two electron-deficient azaaryls and one electron-deficient aryl in high total yield with high diastereo- and excellent enantioselectivities.