Synthesis Of Amino Acid Derivatives Research Articles

Synthesis of 3-((4-Hydroxyphenyl)amino)propanoic Acid Derivatives as Promising Scaffolds for the Development of Antimicrobial Candidates Targeting Multidrug-Resistant Bacterial and Fungal Pathogens.

Infections caused by multidrug-resistant bacterial and fungal pathogens represent a significant global health concern, contributing to increased morbidity and mortality rates. Therefore, it is crucial to develop novel compounds targeting drug-resistant microbial strains. Herein, we report the synthesis of amino acid derivatives bearing an incorporated 4-hydroxyphenyl moiety with various substitutions. The resultant novel 3-((4-hydroxyphenyl)amino)propanoic acid derivatives 2-37 exhibited structure-dependent antimicrobial activity against both ESKAPE group bacteria and drug-resistant Candida species. Furthermore, these derivatives demonstrated substantial activity against Candida auris, with minimum inhibitory concentrations ranging from 0.5 to 64 µg/mL. Hydrazones 14-16, containing heterocyclic substituents, showed the most potent and broad-spectrum antimicrobial activity. This activity extended to methicillin-resistant Staphylococcus aureus (MRSA) with MIC values ranging from 1 to 8 µg/mL, vancomycin-resistant Enterococcus faecalis (0.5-2 µg/mL), Gram-negative pathogens (MIC 8-64 µg/mL), and drug-resistant Candida species (MIC 8-64 µg/mL), including Candida auris. Collectively, these findings underscore the potential utility of the novel 3-((4-hydroxyphenyl)amino)propanoic acid scaffold for further development as a foundational platform for novel antimicrobial agents targeting emerging and drug-resistant bacterial and fungal pathogens.

C<sub>60</sub> Fullerene Amino Acid Derivatives: Synthesis and Biomedical Applications

Water-soluble forms of fullerene C60 possess unique physicochemical and biological properties, making them promising candidates for the development of various drugs in the fields of medicine and veterinary science. Of particular interest are studies on the synthesis and characterization of C60 fullerene derivatives with biogenic additives such as amino acids and peptides. This review focuses on different approaches to the synthesis of amino acid derivatives of fullerene C60 and their promising biomedical applications.

CdSe nanoplatelets as photocatalyst for organic photochemistry: Synthesis of amino acid derivatives by decarboxylative alkylation of aldimines

Colloidal semiconductor two dimensional CdSe nanoplatelets (NPLs) have been widely applied in photophysics, while rarely used in photocatalytic reactions. Here we show that CdSe NPLs act as photocatalyst in visible light-driven radical alkylation of aldimines, with 2,2′-bipyridine (BPY) as an additive. The photocatalytic reaction gave amino-acid derivatives in reliably good yields with various alkyl radical precursors. Furthermore, CdSe NPLs recycled from the reactions remain active and can be reused. The structural and photoelectric properties of fresh and recycled NPLs were characterized using XRD, XPS, TEM, EDS, TRPL, DRS and electrochemical analysis, revealing that BPY can bind to the surface defects of NPLs and adjust the relative oxidation and reduction potentials. As the synthesis of CdSe NPLs is low-cost, convenient and available at industrial scales, the results suggest NPLs could serve as a practical choice of photocatalyst for organic photochemistry.

Synthesis of Amino Acid Derivatives via Free Carbene Insertion

Key words spiro phosphamide catalysis - carbene insertion - amino acid derivatives - enantioselectivity

Design and Synthesis of Amino Acid Derivatives via Diethyl Acetadimalonate and Late‐Stage Modification by Chemical Methods

AbstractWe report various unusual amino acid derivatives containing heterocycles and heteroatoms (S, O, N) via diethyl acetadimalonate as a glycine equivalent and carried out further chemical transformations to modify these unusual amino acid derivatives. Sulfur‐containing halo and alkene derivatives are prepared, and these substrates are further modified by Suzuki‐Miyaura cross‐coupling reaction, cross metathesis sequence and selective formation of sulfoxide and sulfone derivatives. We also report oxazole‐containing amino acid derivative by using TosMIC.

Simple and Effective Derivatization of Amino Acids with 1-Fluoro-2-nitro-4-(trifluoromethyl)benzene in a Microwave Reactor for Determination of Free Amino Acids in Kombucha Beverages.

Kombucha is a fermentation product of sweetened tea with a symbiotic culture of acetic acid and yeast bacteria, consumed worldwide for its health-promoting properties. Few reports can be found about free amino acids among the health-promoting compounds found and determined in kombucha. These compounds influence the sensory properties of kombucha, and they are precursors of bioactive compounds, which have a significant role as neurotransmitters and are involved in biological functions. The presented studies proposed a convenient, simple, and “more green” procedure of the synthesis of amino acid derivatives, assisted by microwave energy, followed by chromatographic determination. The structure of 1-Fluoro-2-nitro-4-(trifluoromethyl)benzene was used as a suitable reagent for the derivatization of free amino acids in fermented kombucha beverages prepared from selected dry fruit such as Crataegus L., Morus alba L., Sorbus aucuparia L., Berberis vulgaris L., Rosa canina L., and black tea. The obtained results were discussed regarding the tested beverages’ application as a source of amino acids in one’s daily diet. The obtained results point out that the proposed microwave-assisted derivatization procedure prior to HPLC analyses allows for a significant time reduction and the limitation of using organic reagents.

Design and synthesis of amino acid derivatives containing hydantoin and thiazolidine moieties

Design and synthesis of amino acid derivatives containing hydantoin and thiazolidine moieties

Design and synthesis of amino acid derivatives of substituted benzimidazoles and pyrazoles as Sirt1 inhibitors.

Owing to its presence in several biological processes, Sirt1 acts as a potential therapeutic target for many diseases. Here, we report the structure-based designing and synthesis of two distinct series of novel Sirt1 inhibitors, benzimidazole mono-peptides and amino-acid derived 5-pyrazolyl methylidene rhodanine carboxylic acid. The compounds were evaluated for in vitro enzyme-based and cell-based Sirt1 inhibition assay, and cytotoxic-activity in both liver and breast cancer cells. The tryptophan conjugates i.e.13h (IC50 = 0.66 μM, ΔGbind = −1.1 kcal mol−1) and 7d (IC50 = 0.77 μM, ΔGbind = −4.4 kcal mol−1) demonstrated the maximum efficacy to inhibit Sirt1. The MD simulation unveiled that electrostatic complementarity at the substrate-binding-site through a novel motif “SLxVxP(V/F)A” could be a cause of increased Sirt1 inhibition by 13h and 13l over Sirt2 in cell-based assay, as compared to the control Ex527 and 7d. Finally, this study highlights novel molecules 7d and 13h, along with a new key hot-spot in Sirt1, which could be used as a starting lead to design more potent and selective sirtuin inhibitors as a potential anticancer molecule.

Co-Catalyzed Transannulation of Pyridotriazoles with Isothiocyanates and Xanthate Esters.

An efficient radical transannulation reaction of pyridotriazoles with isothiocyanates and xanthate esters was developed. This method features conversion of pyridotriazoles into two N-fused heterocyclic aromatic systems-imino-thiazolopyridines and oxo-thiazolopyridine derivatives-via one-step Co(II)-catalyzed transannulation reaction proceeding via a radical mechanism. The synthetic usefulness of the developed method was illustrated in the synthesis of amino acid derivatives and further transformations of obtained reaction products.

Synthesis of Amino Acid Derivatives from Glycine Derivatives and Ketones/Aldehydes

Key words photocatalysis - organocatalysis - glycine derivatives - ketones - aldehydes - dehydrogenative coupling

Chiral donor\u2013acceptor azetines as powerful reactants for synthesis of amino acid derivatives

Coupling reactions of amines and alcohols are of central importance for applications in chemistry and biology. These transformations typically involve the use of a reagent, activated as an electrophile, onto which nucleophile coupling results in the formation of a carbon-nitrogen or a carbon–oxygen bond. Several promising reagents and procedures have been developed to achieve these bond forming processes in high yields with excellent stereocontrol, but few offer direct coupling without the intervention of a catalyst. Herein, we report the synthesis of chiral donor–acceptor azetines by highly enantioselective [3 + 1]-cycloaddition of enoldiazoacetates with aza-ylides and their selective coupling with nitrogen and oxygen nucleophiles via 3-azetidinones to form amino acid derivatives, including those of peptides and natural products. The overall process is general for a broad spectrum of nucleophiles, has a high degree of electronic and steric selectivity, and retains the enantiopurity of the original azetine.

Globally Distributed Drug Discovery of New Antibiotics: Design and Combinatorial Synthesis of Amino Acid Derivatives in the Organic Chemistry Laboratory

An experiment for the synthesis of N-acyl derivatives of natural amino acids has been developed as part of the Distributed Drug Discovery (D3) program. Students use solid-phase synthesis techniques to complete a three-step, combinatorial synthesis of six products, which are analyzed using LC–MS and NMR spectroscopy. This protocol is suitable for introductory organic laboratory students and has been successfully implemented at multiple academic sites internationally. Accompanying prelab activities introduce students to SciFinder and to medicinal chemistry design principles. Pairing of these activities with the laboratory work provides students an authentic and cohesive research project experience.

Amino Acid-Derived trans- N-Chloroformylimidazolidinones: Scalable, Stereoselective Synthesis, Structure, and Utility.

N-acyl imidazolidinones, which are key intermediates in the stereoselective synthesis of amino acids by "self-regeneration of stereochemistry" methods, are classically made by only moderately diastereoselective methods. We now report that cyclization of pivaldimino-amides with phosgene in the presence of pyridine may be made fully diastereoselective for the trans-N-chloroformylimidazolidinones, and we detail the conformational features of the products. We show that despite the presence of the electrophilic carbamoyl chloride function the products show remarkable stability and may be deprotonated to form enolates with useful reactivity for the synthesis of amino acid derivatives.

Synthesis of amino acid derivatives of 5-alkoxy-3,4-dihalo-2(5H)-furanones and their preliminary bioactivity investigation as linkers.

A series of amino acid derivatives are successfully synthesized via a metal-free C-N coupling reaction of 5-alkoxy-3,4-dihalo-2(5H)-furanones and amino acids. Their structures are well characterized with 1H NMR, 13C NMR, ESI-MS and elemental analysis. As potential linkers of the 2(5H)-furanone unit with other drug moieties containing a hydroxyl or amino group, the effect of amino acids is investigated by comparison with other 2(5H)-furanone compounds by constructing C-O/C-S bonds. The preliminary results of the biological activity assay by the MTT method on a series of cancer cell lines in vitro reveal that the introduction of amino acids basically has no toxic effect. This can lead to these 2(5H)-furanone derivatives being further well-linked with other bioactive moieties with amino or hydroxy groups as expected. Thus, the biological activity assay gives a direction for the design of bioactive 2(5H)-furanones based on these amino acid linkers.

2‐Keto‐3‐Deoxy‐l‐Rhamnonate Aldolase (YfaU) as Catalyst in Aldol Additions of Pyruvate to Amino Aldehyde Derivatives

Abstract4‐Hydroxy‐2‐keto acid derivatives are versatile building blocks for the synthesis of amino acids, hydroxy carboxylic acids and chiral aldehydes. Pyruvate aldolases are privileged catalysts for a straightforward access to this class of keto acid compounds. In this work, a Class II pyruvate aldolase from Escherichia coli K‐12, 2‐keto‐3‐deoxy‐l‐rhamnonate aldolase (YfaU), was evaluated for the synthesis of amino acid derivatives of proline, pipecolic acid, and pyrrolizidine‐3‐carboxylic acid. The aldol addition of pyruvate to N‐protected amino aldehydes was the key enzymatic aldol addition step followed by catalytic intramolecular reductive amination. The corresponding N‐Cbz‐amino‐4‐hydroxy‐2‐keto acid (Cbz=benzyloxycarbonyl) precursors were obtained in 51–95% isolated yields and enantioselectivity ratios from 26:74 to 95:5, with chiral α‐substituted N‐Cbz‐amino aldehydes. (S)‐N‐Cbz‐amino aldehydes gave aldol adducts with preferentially (R)‐configuration at the newly formed stereocenter, whereas the contrary is true for (R)‐N‐Cbz‐amino aldehydes. Addition reactions to achiral amino aldehydes rendered racemic aldol adducts. Molecular models of the pre‐reaction ternary complexes YfaU‐pyruvate enolate‐acceptor aldehyde were constructed to explain the observed stereochemical outcome of the reactions. Catalytic reductive amination of the aldol adducts yielded 4‐hydroxy‐2‐pipecolic acid, and unprecedented C‐5 substituted 4‐hydroxyproline and pyrrolizidine‐3‐carboxylic acid derivatives.magnified image

Proton Channels on Molecular Electrocatlaysts for Hydrogenase Mimics

Hydrogenases interconvert H2 and protons at high rates and with high energy efficiencies, providing inspiration for the development of molecular catalysts. Studies designed to determine how the protein scaffold can influence a catalytically active site have led to the synthesis of amino acid derivatives of [Ni(PR 2NR' 2)2]2+ complexes, [Ni(PCy 2NAmino acid 2)2]2+ (CyAA). It is shown that these CyAA derivatives can electrochemically catalyze fully reversible H2 production/oxidation, a feature reminiscent of enzymes. The reversibility is achieved in acidic aqueous solutions, 1 atm 25% H2/Ar, and elevated temperatures (tested up to 70 ¢ªC) for the glycine (CyGly), arginine (CyArg), and arginine methyl ester (CyArgOMe) derivatives. At pH=1 and 70 C, rates of up to ~300 s-1 H2 production and 20 s-1 H2 oxidation 348 K are observed. The effect of higher pressure and the behavior of complexes without an outer coordination sphere will be discussed. These observations demonstrate that outer coordination sphere amino acids work in synergy with the active site in and can play an equally important role for synthetic molecular electrocatalysts as the protein scaffold does for redox active enzymes.

Synthesis of α-amino acid derivatives and peptides via enantioselective addition of masked acyl cyanides to imines.

A general, asymmetric synthesis of amino acid derivatives is reported. Masked acyl cyanide (MAC) reagents are shown to be effective umpolung synthons for enantioselective additions to N-Boc-aldimines. The reactions are catalyzed by a modified cinchona alkaloid, which can function as a bifunctional, hydrogen bonding catalyst, and afford adducts in excellent yields (90–98%) and high enantioselectivities (up to 97.5:2.5 er). Unmasking the addition products gives acyl cyanide intermediates that are intercepted by a variety of nucleophiles to afford α-amino acid derivatives. Notably, the methodology provides an alternative method for peptide bond formation.

Indium metal-organic frameworks as high-performance heterogeneous catalysts for the synthesis of amino acid derivatives.

Indium metal-organic frameworks (MOFs) were first used as recyclable heterogeneous Lewis acid catalysts for the synthesis of amino acid derivatives with excellent conversion yields. Moreover, exposed ether groups (Lewis basic sites) on the pore walls of In-MOF 2 could activate trimethylsilyl cyanide, forming hypervalent silicate intermediates, as proven by (29)Si NMR.

Palladium-Catalyzed Stille-Type Coupling of N-Acyl Iminium Ions with Distannanes: A Multicomponent Synthesis of α-Amidostannanes

The palladium-catalyzed three-component coupling of imines, acid chlorides, and hexabutyldistannane is described. This results in the synthesis of various α-amidostannanes in good yields, without the use of strong nucleophilic organometallic reagents. The reaction is believed to proceed via a Stille-type cross coupling of an in situ-generated N-acyl iminium salt with Bu3SnSnBu3 and reaches completion within 1 h at ambient temperature using simple, unligated Pd2dba3 as a catalyst. Combining the formation of α-amidostannanes with lithiation and carboxylation allows the overall synthesis of amino acid derivatives in two steps from imines, acid chlorides, and CO2.

Propanephosphonic Acid Anhydride (T3P®) - A Benign Reagent for Diverse Applications Inclusive of Large-Scale Synthesis

Propanephosphonic acid anhydride (T3P®) is a prevailing coupling and dehydrating agent with many desirable properties which render it a reagent of choice for a plethora of reactions and, befittingly, its application in organic synthesis is rapidly increasing. Since its introduction as a peptide coupling agent in 1980, the realm of applications of T3P has expanded. Currently its use is found in a broad range of reactions, including condensation, functional group transformation, heterocycles preparation, rearrangements, and catalysis. It offers several advantages over traditional reagents, such as high yield, chemical and optical purity, broad functional group tolerance and easy work-up. The reagent is attractive for large-scale synthesis as well, and particularly so for multi-kilogram scale preparations of drug molecules. This article reviews the hitherto reported applications of T3P as a reagent in organic synthesis. Focus is also placed on the use of T3P for large-scale synthesis. 1 Introduction 2 Structure and Preparation 3 T3P in Peptide Chemistry 3.1 As a Coupling Agent 3.2 Synthesis of Amino Acid Derivatives and Peptidomimetics 4 General Applications 4.1 As a Carboxylic Acid Activator 4.2 As a Dehydrating Agent 4.3 Synthesis of Heterocycles 4.4 Oxidation Reactions 4.5 Carbon–Carbon Bond Formation 4.6 Rearrangement Reactions 4.7 Synthesis of Drugs on Laboratory and Large Scales 5 Recent Applications 6 Conclusion