Quaternary Amino Acids Research Articles

Role of Quaternary Aminoacid Derivatives and Ion Homeostasis in Amelioration of Salinity Stress

Salinity is a detriment to plant production throughout the world. Salinity impacts the quality of irrigation water. Understanding salt stress in plants necessitates complex physiological and metabolic stages. Preserving turgescent cells and regulating the water potential to maintain a proper water balance among the key responsibilities of osmoprotectants, long-term, high salt doses can slow down plant growth and development by interfering with physiological processes like nutrient imbalance, membrane damage, enzyme inhibition and metabolic dysfunctions like photosynthesis, hormone production and ion homeostasis, all of which can result in plant death. Hyperionic and hyperosmotic stress are also caused by prolonged, high salt doses. Osmolytes (such as proline and glycine betaine) accumulate under different salt levels, antioxidant enzyme activities increase and eventually some of the negative effects of NaCl toxicity on plants are mitigated. Plants under salt stress may have higher concentrations of reactive oxygen species (ROS) such as superoxide radicals (O2) and hydrogen peroxide (H2O2). Ion homeostasis is crucial for plants during abiotic stress conditions.

Synergistic Pd/Cu Catalysis for the Synthesis of Unnatural Quaternary Amino Acids

Synergistic Pd/Cu Catalysis for the Synthesis of Unnatural Quaternary Amino Acids

Discovery and Characterization of Pyridoxal 5'-Phosphate-Dependent Cycloleucine Synthases.

Pyridoxal 5'-phosphate (PLP)-dependent enzymes are the most versatile biocatalysts for synthesizing nonproteinogenic amino acids. α,α-Disubstituted quaternary amino acids, such as 1-aminocyclopentane-1-carboxylic acid (cycloleucine), are useful building blocks for pharmaceuticals. In this study, starting with the biosynthesis of fusarilin A, we discovered a family of PLP-dependent enzymes that can facilitate tandem carbon-carbon forming steps to catalyze an overall [3 + 2]-annulation. In the first step, the cycloleucine synthases use SAM as the latent electrophile and an in situ-generated enamine as the nucleophile for γ-substitution. Whereas previously characterized γ-replacement enzymes protonate the resulting α-carbon and release the acyclic amino acid, cycloleucine synthases can catalyze an additional, intramolecular aldol or Mannich reaction with the nucleophilic α-carbon to form the substituted cyclopentane. Overall, the net [3 + 2]-annulation reaction can lead to 2-hydroxy or 2-aminocycloleucine products. These studies further expand the biocatalytic scope of PLP-dependent enzymes.

Metal-Free One-Pot Domino Synthesis of Oxazolidinethione Derivatives of Quaternary Amino Acids from α-Amino Esters and Aldehydes Using CS2.

We present a streamlined, metal-free, one-pot domino approach to efficiently synthesize oxazolidinethione derivatives containing substituted quaternary amino acids. This method employs α-amino esters, aldehydes, and CS2 under mild conditions, constructing three new bonds (C-N, C-C, and C-O) to produce oxazolidinethione compounds featuring a quaternary center and a beta-hydroxy derivative in high yields. This scalable protocol enables the creation of libraries of biologically significant, intricate amino acid derivatives using amino esters and aldehydes.

Cu-catalyzed asymmetric regiodivergent electrosynthesis and its application in the enantioselective total synthesis of (-)-fumimycin

Quaternary amino acids are one of the essential building blocks and precursors of medicinally important compounds. Various synthetic strategies towards their synthesis have been reported. On the other hand, developing core-structure-oriented cross-dehydrogenative coupling (CDC) reactions, is a largely unsolved problem. Herein, we describe a copper-catalyzed regiodivergent electrochemical CDC reaction of Schiff bases and commercially available hydroquinones to obtain three classes of chiral quaternary amino acid derivatives for the efficient assembly of complex scaffolds with excellent stereocontrol. The electrochemical anodic oxidation process with slow releasing of quinones serves as an internal syringe pump and provides high levels of reaction efficiency and enantiomeric control. The utility of this strategy is highlighted through the synthetic utility in the asymmetric total synthesis of (-)-fumimycin.

Stereoselective Biocatalytic α-Deuteration of L-Amino Acids by a Pyridoxal 5'-Phosphate-Dependent Mannich Cyclase.

α-Deuterated amino acids are valuable building blocks for developing deuterated drugs, and are important tools for studying biological systems. Biocatalytic deuteration represents an attractive strategy to directly access enantiopure α-deuterated amino acids. Here, we show that a PLP-dependent Mannich cyclase, LolT, involved in the biosynthesis of loline alkaloids, is capable of deuterating a diverse range of L-amino acids, including basic and acidic, nonpolar and polar, aliphatic and aromatic amino acids. Furthermore, complete deuteration of many amino acids can be achieved within minutes with exquisite control on the site- and stereoselectivity. During the course of this investigation, we also unexpectedly discovered that LolT exhibits β-elimination activity with L-cystine and O-acetyl-L-serine, confirming our previous hypothesis based on structural and phylogenetic analysis that LolT, a Cα-C bond forming enzyme, is evolved from a primordial Cβ-S lyase family. Overall, our study demonstrates that LolT is an extremely versatile biocatalyst, and can be used for not only heterocyclic quaternary amino acid biosynthesis, but also biocatalytic amino acid deuteration.

β-Turn Induction by a Diastereopure Azepane-Derived Quaternary Amino Acid.

β-Turns are one of the most common secondary structures found in proteins. In the interest of developing novel β-turn inducers, a diastereopure azepane-derived quaternary amino acid has been incorporated into a library of simplified tetrapeptide models in order to assess the effect of the azepane position and peptide sequence on the stabilization of β-turns. The conformational analysis of these peptides by molecular modeling, NMR spectroscopy, and X-ray crystallography showed that this azepane amino acid is an effective β-turn inducer when incorporated at the i + 1 position. Moreover, the analysis of the supramolecular self-assembly of one of the β-turn-containing peptide models in the solid state reveals that it forms a supramolecular helical arrangement while maintaining the β-turn structure. The results here presented provide the basis for the use of this azepane quaternary amino acid as a strong β-turn inducer in the search for novel peptide-based bioactive molecules, catalysts, and biomaterials.

Molformer: Motif-Based Transformer on 3D Heterogeneous Molecular Graphs

Procuring expressive molecular representations underpins AI-driven molecule design and scientific discovery. The research mainly focuses on atom-level homogeneous molecular graphs, ignoring the rich information in subgraphs or motifs. However, it has been widely accepted that substructures play a dominant role in identifying and determining molecular properties. To address such issues, we formulate heterogeneous molecular graphs (HMGs) and introduce a novel architecture to exploit both molecular motifs and 3D geometry. Precisely, we extract functional groups as motifs for small molecules and employ reinforcement learning to adaptively select quaternary amino acids as motif candidates for proteins. Then HMGs are constructed with both atom-level and motif-level nodes. To better accommodate those HMGs, we introduce a variant of the Transformer named Molformer, which adopts a heterogeneous self-attention layer to distinguish the interactions between multi-level nodes. Besides, it is also coupled with a multi-scale mechanism to capture fine-grained local patterns with increasing contextual scales. An attentive farthest point sampling algorithm is also proposed to obtain the molecular representations. We validate Molformer across a broad range of domains, including quantum chemistry, physiology, and biophysics. Extensive experiments show that Molformer outperforms or achieves the comparable performance of several state-of-the-art baselines. Our work provides a promising way to utilize informative motifs from the perspective of multi-level graph construction. The code is available at https://github.com/smiles724/Molformer.

Laboratory Scale Continuous Flow Systems for the Enantioselective Phase Transfer Catalytic Synthesis of Quaternary Amino Acids.

The use of stereoselective phase-transfer catalysis as a reliable method for the enantioselective synthesis of optically active α-amino acid derivatives using achiral Schiff base esters has been well-developed in batch in the last 40 years. Recently, continuous flow technology has become of great interest in the academy and industry, since it offers safer process operating conditions and higher efficiency compared to a traditional batch processing. Herein, we wish to report the first example of enantioselective phase transfer benzylation of alanine Schiff base ester, under continuous flow conditions. Two different methodologies were investigated: a liquid-solid phase transfer catalytic benzylation using a packed-bed reactor and a liquid-liquid phase transfer catalytic benzylation in continuous stirred-tank reactors. Liquid-liquid phase transfer process in flow showed slightly better productivity than the batch process, while solid-liquid phase transfer benzylation proved much more advantageous in terms of productivity and space-time yield. Furthermore, continuous flow system allowed the isolation of benzylated product without any work up, with a significant simplification of the process. In both cases, phase transfer asymmetric benzylation promoted by Maruoka catalyst demonstrated high enantioselectivity of target quaternary amino ester in flow, up to 93% ee.

MODIFICATION OF MONTMORILLONITE FOR OBTAINING NANOCOMPOSITES BASED ON POLAR POLYMERS

This review covers almost all known categories of compounds used to modify montmorillonite to obtain nanocomposites based on polar polymers. Organic modifiers such as quaternary ammonium ions, quaternary phosphonium ions, amino acids and other organic compounds are commonly used to modify montmorillonite (MMT). The main directions of scientific research in this field are considered, namely the modification of MMT with ammonium surfactants, phosphonium surfactants, amino acids and nonionic surfactants. The review used 67 sources related to peer-reviewed publications, mostly from the last 10-15 years. The largest number of publications devoted to the modification of MMT was published in the period from 2004 to 2016. Nanocomposites based on epoxy resins are especially widely presented in the literature. Epoxy-based materials have been used for many years as convenient matrices for dispersing MMT due to the advantages of properties of the obtained polymer nanocomposites, such as mechanical strength, non-flammability and thermal stability. The methods of surface modification of MMT with organic modifiers considered in the article are a powerful tool for the production of polymer nanocomposite materials based on polar polymers. Amine modification of MMT allowed the formation of highly effective materials, in particular epoxy/MMT materials. These nanocomposites have demonstrated extraordinary material properties compared to virgin polymers and can therefore be used as an alternative to conventional materials such as steel and wood, reducing the cost and weight of products. Nanocomposites based on polar polymers occupy an important place among all polymer nanocomposites as modern materials used in the aerospace, automotive and electrical industries.

Design of Photoredox-Catalyzed Giese-Type Reaction for the Synthesis of Chiral Quaternary α-Aryl Amino Acid Derivatives via Clayden Rearrangement.

Chiral quaternary α-aryl amino acids are biologically valued but synthetically challenging building blocks. Herein, we report a strategy for the synthesis of molecular architectures by unifying a photoredox catalytic asymmetric Giese-type reaction and Clayden rearrangement. A new class of chiral Karady-Beckwith dehydroalanines is designed and serves as a versatile handle for the photoredox-mediated highly stereoselective Giese-type reaction with feedstock carboxylic acids and tertiary amines. Subsequent Clayden rearrangement delivers chiral quaternary α-aryl amino acid derivatives with high stereoselectivity. The versatile approach offers a reliable source for the assembly of highly demanding chiral building blocks.

Asymmetric Synthesis of Quaternary Amino Acid Esters

Asymmetric Synthesis of Quaternary Amino Acid Esters

Construction of Quaternary Allylic Amino Acid Derivatives through Palladium-Catalyzed Allylic Alkylation Reaction of Azlactones with Vinyl Aziridine

AbstractA highly efficient Pd-catalyzed allylic alkylation reaction of azlactones with vinyl aziridine has been achieved for the first time to access­ functionalized quaternary allylic amino acid derivatives (17 examples, up to 89% yield and 80% ee). Moreover, the broad scope and easy transformations of the products reinforce the value of this approach, which can enrich the chemistry of quaternary allylic amino acid derivatives.

Nickel/Copper-Catalyzed Synthesis of Tetrasubstituted Amino Acids

Key words nickel catalysis - copper catalysis - benzylation - aldimine esters - quaternary amino acids

Chiral Bicyclic Imidazole-Catalyzed Direct Enantioselective C -Acetylation of Indolones

Chiral Bicyclic Imidazole-Catalyzed Direct Enantioselective <i>C</i> -Acetylation of Indolones

Delignification of unbleached pulp by ternary deep eutectic solvents

Abstract The processing of lignocellulosic materials is very limited because of their low solubility in water and some organic solvents. Fifteen ternary deep eutectic solvents (DESs) were prepared and tested as solvents suitable for delignification of unbleached pulp. The selected ternary DESs are composed of quaternary ammonium salts and amino acids as hydrogen-bond acceptors, and organic acids and polyvalent alcohols as hydrogen bond donors, with molar ratios varying for the individual components. The delignification efficiency is significantly influenced by the degree of penetration of the solvent into the pulp fibre structure. Therefore, the density and viscosity analysis of individual solvents was performed. Unbleached beech pulp with initial kappa number 13.9 was treated with the prepared DESs. The kappa number indicates the residual lignin content or the bleachability of pulp. The efficiency of the solvents ranged from 1.4% to 28.1%. The most suitable for the pretreatment of fibres, based on lignin removal efficiency, were found to be three DESs, in the following order: malonic acid/choline chloride/1,3-propanediol (1:1:3) &gt; choline chloride/acetamide/lactic acid (1:2:3) &gt; choline chloride/urea/lactic acid (1:2:3).

Amine-Directed Palladium-Catalyzed C-H Halogenation of Phenylalanine Derivatives.

An efficient primary-amine-directed, palladium-catalyzed C-H halogenation (X=I, Br, Cl) of phenylalanine derivatives is reported on a range of quaternary amino acid (AA) derivatives thanks to suitable conditions employing trifluoroacetic acid as additive. The extension of this original native functionality-directed ortho-selective halogenation was even demonstrated with the more challenging native phenylalanine as tertiary AA.

A comprehensive study of amino acids based ionic liquids as green lubricants for various contacts

In this paper, a group of quaternary ammonium amino acid ionic liquids (QAAA ILs) prepared by coupling the tetrabutylammonium cation with fourteen types of natural amino acids as base lubricant were investigated for steel/steel, steel/copper and steel/aluminum contacts at ambient temperature and elevated temperature. The corrosion resistance and tribological ability of various QAAA ILs was determined. The influences of various anionic structures on kinematic viscosity, corrosivity, thermal stability and tribological properties of the ILs were discussed in detailed. The copper strip corrosion test results showed that the present ILs have been proved to be almost non-corrosive. Tribological behaviors results displayed that the present ILs exhibit extremely eminent friction reduction and antiwear properties. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) analysis revealed that a protective lubricating film is formed on the surface of contact mainly through a polarity induced physical adsorption when QAAA ILs are selected as neat lubricants, which plays a key role in reducing friction and wear between the moving mechanical interface.

δ-Valerolactamic Quaternary Amino Acid Derivatives: Enantiodivergent Synthesis and Evidence for Stereodifferentiated β-Turn-Inducing Properties.

Enantiopure (R) and (S) cyclic α,α-disubstituted amino acid derivatives displaying a δ-valerolactam side chain were prepared from a common isoxazolidine precursor. The (R)-configured δ-valerolactam 11 was converted into diastereoisomeric pseudopeptides to investigate its ability to induce secondary structures in peptidomimetics. Conformational studies of these pseudopeptides were carried out in the solid state (X-ray diffraction), in solution (NMR analyses), and in silico (computer-aided conformational analysis), which demonstrated that such quaternary amino acids induce β-turn conformations stable enough to be retained in polar media (DMSO). Incorporation of this new type of α,α-disubstituted amino acid into a representative pseudopeptidic sequence by N- then C-elongation and N-debenzylation is also described herein and could serve for the synthesis of various structured peptidomimetics.

1,3‐Dipolar Cycloaddition between Dehydroalanines and C,N‐Cyclic Azomethine Imines: Application to Late‐Stage Peptide Modification

AbstractA non‐catalytic, mild, and easy‐to‐handle protecting group switched 1,3‐dipolar cycloaddition (1,3‐DC) between bi‐ or mono‐N‐protected Dha and C,N‐cyclic azomethine imines, which afford various quaternary amino acids with diverse scaffolds, is disclosed. Specifically, normal‐electron‐demand 1,3‐DC reaction occurs between bi‐N‐protected Dha and C,N‐cyclic azomethine imines, while inverse‐electron‐demand 1,3‐DC reaction occurs between mono‐N‐protected Dha and C,N‐cyclic azomethine imines. Above all, the reactions can be carried out between peptides with Dha residues at the position of interest and C,N‐cyclic azomethine imines, both in homogeneous phase and on resins in SPPS. It provides a new toolkit for late‐stage peptide modification, labeling, and peptide–drug conjugation. To shed light on the high regioselectivity of the reaction, DFT calculations were carried out, which were qualitatively consistent with the experimental observations.