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. Titanium tetrachloride has proven highly effective as a coupling reagent for the one-pot formation of esters from carboxylic acids and alcohols operating under mild and neutral conditions. Notably, the reaction eliminates the need for bases, yielding carboxylic esters in high purity and yields. The method is efficient, even with long-chain carboxylic acids, and operates well with primary alcohols in dichloromethane. Steric hindrance, potentially present in carboxylic acids, has a moderate effect on the reaction. Alcohol substrates that easily form stable carbocations require, instead, the use of non-polar solvents like hexane for the reaction.

Evaluation of the Shelf life of Ready-to-Eat Fresh Bamboo Sprouts (Phyllostachys edulis) Packaged in a Modified Atmosphere or Vacuum: A Comparative Study.

During the last decades, the consumption of bamboo sprouts (Phyllostacys edulis) has increased because they are considered a "superfood". However, this product is characterized by a short shelf life due to the deterioration in quality parameters. The aim of this study was to investigate the application of two modified atmosphere packaging (MAP) systems (MAP1: 2% O2, 5% CO2, 93% N2 and MAP2: 3% O2, 7% CO2, 90% N2) to fresh-shelled ready-to-eat bamboo sprouts and compare these packaging systems with vacuum packaging during storage for 28 days at 4 °C using heat-sealable polyamide and polyethylene (PA/PE) trays. Several chemical-physical parameters (moisture content, water activity, pH, headspace composition, and firmness) were monitored, as well as CIELab colorimetric parameters and microbial growth. The quantification of selected organic acids was performed via UHPLC. Mathematical kinetic models were applied to study the evolution of total phenol (TPC), flavonoid (TFC), and carotenoid content (TCC) during storage. The evolution of antioxidant potential investigated by ABTS, DPPH, and ß-carotene bleaching tests was also assessed. Results showed that at the end of the storage period, significant variations in the colorimetric parameters are detectable between the sprouts apical portion and the basal one, regardless of both applied MAPs. A linear reduction in both DPPH and ABTS radical scavenging activity was evidenced during storage, regardless of the type of packaging applied. In DPPH test samples packaged in MAP after 28 days of storage, they retain good antioxidant activity, whereas in vacuum, this activity is reduced by 50% compared to the initial value (IC50 values from 24.77 to 32.74 µg/mL and from 24.77 to 71.12 µg/mL for MAP2 and vacuum, respectively).

Peptides Targeting HER2-Positive Breast Cancer Cells and Applications in Tumor Imaging and Delivery of Chemotherapeutics.

Breast cancer represents the most common cancer type and one of the major leading causes of death in the female worldwide population. Overexpression of HER2, a transmembrane glycoprotein related to the epidermal growth factor receptor, results in a biologically and clinically aggressive breast cancer subtype. It is also the primary driver for tumor detection and progression and, in addition to being an important prognostic factor in women diagnosed with breast cancer, HER2 is a widely known therapeutic target for drug development. The aim of this review is to provide an updated overview of the main approaches for the diagnosis and treatment of HER2-positive breast cancer proposed in the literature over the past decade. We focused on the different targeting strategies involving antibodies and peptides that have been explored with their relative outcomes and current limitations that need to be improved. The review also encompasses a discussion on targeted peptides acting as probes for molecular imaging. By using different types of HER2-targeting strategies, nanotechnology promises to overcome some of the current clinical challenges by developing novel HER2-guided nanosystems suitable as powerful tools in breast cancer imaging, targeting, and therapy.

Ultrasound-Assisted Extraction, Chemical Characterization, and Impact on Cell Viability of Food Wastes Derived from Southern Italy Autochthonous Citrus Fruits.

Citrus fruits are one of the principal fruits used to produce juices. Over the years, these fruits have been recognized as new health-promoting agents. In this work, food wastes derived from autochthonous citrus fruits of Southern Italy, named Limone di Rocca Imperiale, Arancia Rossa Moro, and Arancia Bionda Tardivo from Trebisacce, were analyzed. After fresh-squeezing juice, peel and pomace were employed to obtain six different extracts using an ultrasound-assisted method in a hydroalcoholic solvent. The extracts were analyzed in terms of qualitative composition, antioxidant properties, and antiproliferative activity on MCF-7, MDA-MB-231, and BJ-hTERT cell lines. GC-MS and LC-ESI-MS analyses showed different compounds: of note, limonin-hexoside, neodiosmin, obacunone glucoside, and diacetyl nomilinic acid glucoside have been identified as limonoid structures present in all the samples, in addition to different polyphenols including naringenin-glucoside, hesperetin-O-hexoside-O-rhamnoside-O-glucoside, diferuloyl-glucaric acid ester, chlorogenic acid, and the presence of fatty acids such as palmitic, myristic, and linoleic acids. These extracts were able to exert antioxidant activity as demonstrated by DPPH and ABTS assays and, although at higher doses, to reduce the cell viability of different solid tumor cell lines, as shown in MTT assays.

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. Both leptin excess and leptin deficiency, as well as leptin resistance, are correlated with different human pathologies, such as autoimmune diseases and cancers, making leptin and leptin receptor important drug targets. The development of leptin signaling modulators represents a promising strategy for the treatment of cancers and other leptin-related diseases. In the present manuscript, we provide an update review about leptin-activity modulators, comprising leptin mutants, peptide-based leptin modulators, as well as leptin and leptin receptor specific monoclonal antibodies and nanobodies.

Formulation of New Baking (+)-Catechin Based Leavening Agents: Effects on Rheology, Sensory and Antioxidant Features during Muffin Preparation.

The aim of this investigation was to prepare two solid mixtures containing a soluble polymorph of (+)-catechin and mucic (MUC) or tartaric (TAR) acids as new leavening agents. The solid mixtures were based on a polymorph of (+)-catechin, characterized through Powder X-ray Diffraction (PXRD) analysis and assayed in in vitro antioxidant and solubility assays. The dough samples were studied by dynamic rheological tests, while muffins were studied through Headspace Solid-Phase Microextraction (HS-SPME)/ Gas Chromatography-Mass Spectrometry (GC-MS) analysis to identify volatile compounds, in vitro tests to evaluate antioxidant properties, and sensory analyses. TAR powder showed a solubility in water almost one order of magnitude increased with respect to commercial (+)-catechin (40.0 against 4.6 mg mL-1) and increased antioxidant performances. In particular, TAR showed total phenolic content (TPC) and total antioxidant capacity (TAC) values of 0.0298 ± 0.021 and 0.0081 ± 0.0009 meq CT/g, while MUC showed better results in terms of 2,2-diphenyl-1-picrylhydrazyl) acid (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid (ABTS), 0.518 ± 0.015 and 0.112 ± 0.010mg/mL, respectively. MS analysis identified different compounds derived from the lipid oxidation process. Muffins obtained using both powders showed interesting outcomes regarding dough process and appreciable appearance/olfactory/taste/texture profiles. Muffins obtained from TAR-based mixture showed also a total phenolic content of 0.00175 meq CT/g muffin, and almost two times improved TAC and scavenger activity against DPPH radical. The formulated powders could be used as suitable health-promoting ingredients in the food industry.

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

A series of dipeptide systems have been easily achieved through a TiCl4-assisted condensation reaction. The reaction of N-protected amino acids with amino acid methyl esters in pyridine and in the presence of TiCl4 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. The adopted experimental conditions allowed preserving both the protecting groups on the α-amino function and on the side chain functionalities. Furthermore, the preservation of the stereochemical integrity at the amino acid chiral centres has been verified.

Alternative formation of amides and ß-enaminones from aroyl chlorides using the TiCl4-trialkylamine reagent system.

The TiCl4/NR3 reagent system has been successfully employed for the synthesis of amides and ß-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 ß-enaminones as unique or major products. The two developed protocols were investigated with a series of tertiary amines. The reactions, modulated by the presence of TiCl4, provided the corresponding amides or ß-enaminones with satisfactory yields. This paper reports a new method for carbon-carbon bond formation via the reaction of aroyl chlorides with the TiCl4/NR3 reagent system.

Aromatherapy: composition of the gaseous phase at equilibrium with liquid bergamot essential oil.

This work compares the composition at different temperatures of gaseous phase of bergamot essential oil at equilibrium with the liquid phase. A new GC-MS methodology to determine quantitatively the volatile aroma compounds was developed. The adopted methodology involved the direct injection of headspace gas into injection port of GC-MS system and of known amounts of the corresponding authentic volatile compounds. The methodology was validated. This study showed that gaseous phase composition is different from that of the liquid phase at equilibrium with it.

Formation of amides: one-pot condensation of carboxylic acids and amines mediated by TiCl4.

A general procedure for the synthesis of amides via the direct condensation of carboxylic acids and amines in the presence of TiCl4 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. The process takes place with nearly complete preservation of the stereochemical integrity of chiral substrates.

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. Thus the Fms group can be interchangeable with the Fmoc group in the synthesis of N-methylated peptides using standard Fmoc-based strategies. Finally, the absence of racemization during the methylation reaction and the removal of Fms group were demonstrated by synthesising a pair of diastereomeric dipeptides.

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. A single experiment can be performed in order to determine simultaneously the free amino acid and free fatty acid profiles. The analytes of interest are rapidly extracted from the meat matrix and derivatized by using methyl chloroformate. This reagent allows the transformation of the two groups of analytes into the corresponding N-methyloxycarbonyl amino acid methyl esters and fatty acid methyl esters that can easily be extracted and sampled for their further identification and quantitation. The measurement of the obtained amino acid and fatty acid derivatives is performed by GC/MS analysis and their concentrations are calculated by using two appropriate internal standards. The main advantage of the proposed protocol is the determination at the same time of two important classes of analytes that are of great importance in food analysis and characterization. Moreover, minimal sample manipulation and preparation, and reduced total extraction times are required to obtain the response with respect to conventional procedures, in which instead the analysis of both the two classes of compounds must be performed separately. The helpfulness of the protocol was tested in the analysis of a cured meat product that is typical of the South of Italy. The optimized protocol successfully allowed the determination of thirteen free amino acids and six free fatty acids, namely those most abundant in the lipid content of the cured meat product under evaluation.

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. An important aspect of this synthetic strategy is the possibility to selectively deprotect the carboxyl function or alternatively both amino and carboxyl moieties by using the same reagent with a different molar excess and under mild conditions. Furthermore, the adopted procedure keeps unchanged the acid-sensitive side chain protecting groups used in Fmoc-based synthetic strategies.