Efficient Solution-Phase Dipeptide Synthesis Using Titanium Tetrachloride and Microwave Heating.

Microwaves have been successfully employed in the Lewis acid titanium tetrachloride-assisted synthesis of peptide systems. Dipeptide systems with their amino function differently protected with urethane protecting groups have been synthesized in short periods of time and with high yields. The formation of the peptide bond between the two reacting amino acids was achieved in pyridine by using titanium tetrachloride as a condensing agent and heating the reaction mixture with a microwave reactor.

Titanium Tetrachloride-Assisted Direct Esterification of Carboxylic Acids.

Ester compounds, widely found in pharmaceutical and natural products, play a crucial role in organic synthesis, prompting the development of numerous methods for their synthesis. An important chemical approach in synthesizing esters from carboxylic acids involves the activation of the carboxyl function, requiring the conversion of the hydroxyl group into a suitable leaving group. This paper presents the findings of our investigations into an efficient method for producing esters from carboxylic acids and alcohols, using the Lewis acid titanium tetrachloride.

Leptin-Activity Modulators and Their Potential Pharmaceutical Applications.

Leptin, a multifunctional hormone primarily, but not exclusively, secreted in adipose tissue, is implicated in a wide range of biological functions that control different processes, such as the regulation of body weight and energy expenditure, reproductive function, immune response, and bone metabolism. In addition, leptin can exert angiogenic and mitogenic actions in peripheral organs. Leptin biological activities are greatly related to its interaction with the leptin receptor.

Determination of substituent effects on the proton affinities of natural nucleosides by the kinetic method.

The kinetics of the unimolecular dissociations of proton-bound dimers produced by fast-atom bombardment from nucleosides and reference amines enables the evaluation of the proton affinities (PAs) of ribonucleosides. The PAs of cytosine, guanosine, adenosine, uridine, and deoxyuridine have been thus determined. These values and those already available for the corresponding DNA homologues allow the evaluation of the effect of the hydroxyl group in position 2' of the sugar moiety, which lowers the PAs of RNA nucleosides by 0.

Anti-amyloid-β protein agents for the treatment of Alzheimer's disease: an update on emerging drugs.

Introduction: Currently available Alzheimer's disease (AD) therapeutics are only symptomatic, targeting cholinergic and glutamatergic neurotransmissions. Several putative disease-modifying drugs in late-stage clinical development target amyloid-β (Aβ) peptide and tau protein, the principal neurophatological hallmarks of the disease.

Areas Covered: Phase III randomized clinical trials of anti-Aβ drugs for AD treatment were searched in US and EU clinical trial registries and principal biomedical databases until May 2020.

Sensorial frailty: age-related hearing loss and the risk of cognitive impairment and dementia in later life.

The peripheral hearing alterations and central auditory processing disorder (CAPD) associated with age-related hearing loss (ARHL), may impact cognitive disorders in older age. In older age, ARHL is also a significant marker for frailty, another age-related multidimensional clinical condition with a nonspecific state of vulnerability, reduced multisystem physiological reserve, and decreased resistance to different stressors (i.e.

A titanium tetrachloride-based effective methodology for the synthesis of dipeptides.

A series of dipeptide systems have been easily achieved through a TiCl-assisted condensation reaction. The reaction of N-protected amino acids with amino acid methyl esters in pyridine and in the presence of TiCl furnished the corresponding dipeptides with high yields and diastereoselectivity. The reaction was successfully applied to amino acids protected on the α-amino function with different protecting groups.

Leptin Receptor as a Potential Target to Inhibit Human Testicular Seminoma Growth.

Although in past decades the adipokine leptin and its own receptor have been considered as significant cancer biomarkers, their potential involvement in human testicular seminoma growth and progression remains unexplored. Here, we showed that the expression of leptin and its receptor was significantly higher in human testicular seminoma compared with normal adult testis. Human seminoma cell line TCam-2 also expressed leptin along with the long and short isoforms of leptin receptor, and in response to leptin treatment showed enhanced activation of its downstream effectors.

Alternative formation of amides and β-enaminones from aroyl chlorides using the TiCl-trialkylamine reagent system.

The TiCl4/NR3 reagent system has been successfully employed for the synthesis of amides and β-enaminones. The reaction of variously substituted benzoyl chlorides with the TiCl4/NR3 reagent system, by using two different experimental procedures (Method A and Method B), afforded alternatively the corresponding amides and β-enaminones as unique or major products. The two developed protocols were investigated with a series of tertiary amines.

Formation of amides: one-pot condensation of carboxylic acids and amines mediated by TiCl.

A general procedure for the synthesis of amides via the direct condensation of carboxylic acids and amines in the presence of TiCl is reported. The amidation reaction was performed in pyridine at 85 °C with a wide range of substrates providing the corresponding amide products in moderate to excellent yields and high purity. The reaction proceeds with low yields when both the carboxylic acid and the amine are sterically hindered.

N-Methylated α-Amino Acids And Peptides: Synthesis And Biological Activity.

The simplest and minimal modification of a single amino acid or peptide bonds is represented by N-methylation. This can improve the pharmacokinetic properties of biologically active peptides as well as resulting in analogues that show specific biological activity such as enzyme inhibitors, receptor antagonists and agonists, building blocks in combinatorial chemistry for the screening of new potential drugs. Further, structural and conformational studies performed with N-methylated analogues of natural amino acids and peptides enabled to (i) produce stable foldamers with different topology with respect to the helix of natural and endogenous peptides, (ii) confer to modified peptides high stability against proteases and (iii) enhance lipophilicity and bioavailability for pharmacological purposes.

Lewis acid catalysed methylation of N-(9H-fluoren-9-yl)methanesulfonyl (Fms) protected lipophilic α-amino acid methyl esters.

This work reports an efficient Lewis acid catalysed N-methylation procedure of lipophilic α-amino acid methyl esters in solution phase. The developed methodology involves the use of the reagent system AlCl3/diazomethane as methylating agent and α-amino acid methyl esters protected on the amino function with the (9H-fluoren-9-yl)methanesulfonyl (Fms) group. The removal of Fms protecting group is achieved under the same conditions to those used for Fmoc removal.

A novel leptin antagonist peptide inhibits breast cancer growth in vitro and in vivo.

The role of the obesity cytokine leptin in breast cancer progression has raised interest in interfering with leptin's actions as a valuable therapeutic strategy. Leptin interacts with its receptor through three different binding sites: I-III. Site I is crucial for the formation of an active leptin-leptin receptor complex and in its subsequent activation.

Therapeutic potential of leptin receptor modulators.

Leptin, a pleiotropic molecule mainly produced by adipose tissue, was first discovered as a hormone controlling body weight and energy expenditure. In addition, leptin can modulate several processes in peripheral tissues such as immune response, fertility, hematopoiesis and carcinogenesis. The development of molecules that block or stimulate leptin receptor may therefore serve as a potent tool for studying the role of leptin in mammalian physiology and pathology, but it also may open new possibilities for therapy.

C → N and N → C solution phase peptide synthesis using the N-acyl 4-nitrobenzenesulfonamide as protection of the carboxylic function.

In this paper we describe a solution phase peptide synthesis strategy using the 4-nitrobenzenesulfonamido/N-methyl-4-nitrobenzenesulfonamido group as a protecting/activating system of the carboxyl function. The 4-nitrobenzenesulfonamido group is stable during peptide chain elongation (Fmoc chemistry). The N-aminoacyl or N-dipeptidyl-4-nitrobenzensulfonamides, when activated by methylation, can be easily coupled with another amino acid or reconverted into the free-carboxyl function amino acids or peptides.

A one-pot procedure for the preparation of N-9-fluorenylmethyloxycarbonyl-α-amino diazoketones from α-amino acids.

The study describes a new "one-pot" route to the synthesis of N-9-fluorenylmethyloxycarbonyl (Fmoc) α-amino diazoketones. The procedure was tested on a series of commercially available free or side-chain protected α-amino acids employed as precursors. The conversion into the title compounds was achieved by masking and activating the α-amino acids with a single reagent, namely, 9-fluorenylmethyl chloroformate (Fmoc-Cl).

Quantitative determination of fatty acid chain composition in pork meat products by high resolution 1H NMR spectroscopy.

High resolution (1)H NMR spectroscopy was proposed for the determination of the fatty acid chain profile of lipids in pork meat products during ripening. Two typical Mediterranean PDO salami produced in Calabria, a region in the Southern Italy, were chosen as a case of study. Quantitative NMR analysis provided the fatty acid chain profiles of total lipid extracts.

Simultaneous extraction and derivatization of amino acids and free fatty acids in meat products.

In meat products the contents of free amino acids and free fatty acids are two important parameters used to establish their quality. These compounds play a very important role in defining the sensorial characteristics and acceptability of meat products. An innovative procedure for the measurement of free amino acid and fatty acid contents in meat and meat derivatives was developed.

Dry fermented sausages of Southern Italy: a comparison of free amino acids and biogenic amines between industrial and homemade products.

This paper compares some important parameters and the free amino acid and biogenic amine contents of cured industrial and homemade meat products. To this aim, industrial and homemade "soppressata" and "salsiccia", typical dry fermented sausages produced in Southern Italy, were analyzed. The homemade sausages showed a higher level of free biogenic amines than that manufactured industrially, most likely because biogenic amine formation in industrial products is limited by the use of starter cultures.

Spartium junceum aromatic water: chemical composition and antitumor activity.

The purpose of this study was to analyse the chemical composition of Spartium junceum L. (also known as Spanish Broom) aromatic water and to evaluate its cytotoxic activity against a series of human cancer cell lines (melanoma: RPMI 7932; leukemia: K562; breast cancer cell: MCF7-Bart and MCF7-ICLC, colon adenocarcinoma: SW480). The results show that the aromatic water was cytotoxic toward the tumor cell lines analyzed (RPMI 7932, K562, MCF7-Bart, MCF7-ICLC, SW480), while it did not appreciably alter the viability of normal keratinocytes (NCTC 2544) suggesting its potential use as an antitumor agent for cancer treatment and/or prevention.

Transformations of 3-hydroxy steroids with lewis and anhydrous protic acids: the case of pregn-4-en-3β,17α,20β-triol.

The acid-catalyzed dehydration is one of the most important processes, which transforms 3-hydroxy steroids into their corresponding unsaturated derivatives. This reaction is of great importance because it can produce molecules that play a key role in the understanding of the natural metabolism of steroids. Sterol dehydration is generally performed with aqueous acidic systems, and the treatment often affords low yields of the desired compounds and/or complex mixtures of by-products.

Site-selective methylation of N(beta)-nosyl hydrazides of N-nosyl protected alpha-amino acids.

The methylation reaction of N(beta)-nosyl hydrazides of N-nosyl protected alpha-amino acids by using diazomethane shows a controlled regiochemical trend and makes it possible to obtain the corresponding products methylated at specific positions depending on the amount of diazomethane used. The observed selectivity is closely connected with the different acidity of sulfonyl hydrazide, sulfonamide, and acyl hydrazine protons present in the analyzed substrates. The reactivity order of these three diverse reactive sites is supported by theoretical calculations.

An efficient preparation of N-methyl-alpha-amino acids from N-nosyl-alpha-amino acid phenacyl esters.

In this paper we describe a simple and efficient solution-phase synthesis of N-methyl-N-nosyl-alpha-amino acids and N-Fmoc-N-methyl-alpha-amino acids. This represents a very important application in peptide synthesis to obtain N-methylated peptides in both solution and solid phase. The developed methodology involves the use of N-nosyl-alpha-amino acids with the carboxyl function protected as a phenacyl ester and the methylating reagent diazomethane.

A new non-natural arginine-like amino acid derivative with a sulfamoyl group in the side-chain.

Sulfamoylation of the L-ornithine methyl ester side-chain generates a non-natural arginine isostere which can be coupled with N-Fmoc-L-proline to synthesize analogues which maintain the structural characteristics of the biologically important Pro-Arg dipeptide sequence. As a probe of its biological importance, the sulfamoylated amino acid derivative was also incorporated as P1 residue in tripeptide structures matching the C-terminal subsequence of fibrinogen. The reported results demonstrate that the functionalization of L-ornithine side-chain with a neutral sulfamoyl group can generate an arginine bioisostere which can be used for the synthesis of prototypes of a new class of human thrombin inhibitors.