Search Results (137)

Broccoli, a highly valued Brassica vegetable, is renowned for its rich content of bioactive substances, including glucosinolates, phenolic compounds, vitamins, and essential minerals. Glucosinolates (GSLs), secondary plant metabolites, are particularly abundant in broccoli. The global consumption of broccoli has increased due to its high nutritional value. This review examines the essential bioactive compounds in broccoli and their biological properties. Numerous in vitro and in vivo studies have demonstrated that broccoli exhibits various biological activities, including antioxidant, anticancer, antimicrobial, anti-inflammatory, anti-obesity and antidiabetic effects. This review analyzes several aspects of the chemical and biological activity of GSLs and their hydrolysis products, isothiocyanates such as sulforaphane, as well as phenolic compounds. Particular emphasis is placed on sulforaphane’s chemical structure, the reactivity of its isothiocyanate fraction (-NCS), and given the different behavior of SFN enantiomers, a wide and detailed review of the chemical synthesis methods described, by microbial oxidation, or using a chiral ruthenium catalyst and more widely using chiral auxiliaries for synthesizing sulforaphane enantiomers. In addition, the methods of chiral resolution of racemates by HPLC are reviewed, explaining the different chiral fillers used for this resolution and a third section on resolution using the formation of diastereomeric complexes and subsequent separation on achiral columns. Additionally, this review highlights the presence of antimicrobial peptides in broccoli, which have shown potential applications in food preservation and as natural alternatives to synthetic antibiotics. The antimicrobial peptides (AMPs) derived from broccoli target bacterial membranes, enzymes, oxidative stress pathways and inflammatory mediators, contributing to their effectiveness against a wide range of pathogens and with potential therapeutic applications. Full article

Human lactate dehydrogenase A (hLDHA) is a homotetrameric isozyme involved in the conversion of glyoxylate into oxalate in the cytosol of liver cells (hepatocytes) and partially responsible for the overproduction of oxalate in patients with the rare disease called primary hyperoxaluria (PH). Recently, hLDHA inhibition has been validated as a safe therapeutic method to try to control the PH disease. Stiripentol (STP) is an approved drug used in the treatment of seizures associated with Dravet’s syndrome (a severe form of epilepsy in infancy) which, in addition, has been drawing interest in recent years also for potentially treating PH, due to its hLDHA inhibitory activity. In this work, several new STP-related compounds have been synthesized and their hLDHA inhibitory activity has been compared to that of STP. The synthesis of these analogues to STP was accomplished using crossed-aldol condensation guided by lithium enolate chemistry and a successive regioselective reduction of the resulting α,β-unsaturated ketones. The target molecules were obtained as racemates, which were separated into their enantiomers by chiral HPLC. The absolute configurations of pure enantiomers were determined by the modified Mosher’s method and electronic circular dichroism (ECD) spectroscopy. For the inhibitory effect over the hLDHA catalytic activity, a kinetic spectrofluorometric assay was used. All the new synthesized compounds turned out to be more active at 500 μM (46–72% of inhibition percentage) than STP (10%), which opens a new line of study on the possible capacity of these analogues to reduce urinary oxalate levels in vivo more efficiently. Full article

Five chiral, racemic dialkyl α-hydroxyethylphosphonates and α-hydroxyethyl-diarylphosphine oxides were prepared in a scalable manner. Possibilities for the optical resolution of the racemic hydroxyphosphine oxides were explored via diastereomeric complex-forming experiments. The acidic calcium salt of O,O′-dibenzoyl-(2R,3R)-tartaric acid and O,O′-di-p-tolyl-(2R,3R)-tartaric acid were chosen as the resolving agents. The role of the solvent in the enantiomeric discrimination was investigated. The diastereomeric complex could be obtained in a crystalline form for α-hydroxyethyl-diphenylphosphine oxide and α-hydroxyethyl-bis(4-methylphenyl)phosphine oxide. However, in the third case, for α-hydroxyethyl-bis(3,5-dimethylphenyl)phosphine oxide, there was no chiral discrimination. Decomposition of the recrystallized diastereomeric complex followed by decomposition of the complex yielded the target compounds in 77/90% enantiomeric excess. The absolute configuration of the hydroxyethyl-diphenylphosphine oxide was determined by single-crystal X-ray diffraction measurements. The interactions stabilizing the supramolecular associate were evaluated. Full article

This study aimed to optimize the kinetic resolution of building blocks for the synthesis of β-blockers using Candida rugosa lipases, which could be potentially used to synthesize enantiomerically pure β-blockers further. Reaction mixtures were incubated in a thermostated shaker. Qualitative and quantitative analyses of the reaction mixtures were performed using chiral stationary phases and the UPLC-IT-TOF system. Of the 24 catalytic systems prepared, a system containing lipase from Candida rugosa MY, [EMIM][BF₄] and toluene as a two-phase reaction medium and isopropenyl acetate as an acetylating agent was optimal. This resulted in a product with high enantiomeric purity produced via biotransformation, whose enantioselectivity was E = 67.5. Using lipases from Candida rugosa enables the enantioselective biotransformation of the β-blockers building block. The biocatalyst used, the reaction environment, and the acetylating agent significantly influence the efficiency of performer kinetic resolutions. The studies made it possible to select an optimum system, a prerequisite for obtaining a product of high enantiomeric purity. As a result of the performed biotransformation, the (S)-enantiomer of the β-blocker derivative was obtained, which can be used to further synthesize enantiomerically pure β-blockers. Full article

The hydrolase-catalyzed kinetic resolution of fluorinated racemates of 3-arylcarboxylic acids is described. Hydrolysis of ethyl esters of fluorinated acids by esterases and hydrolases in all cases resulted in the formation of hydrolyzed (S)-carboxylic acids and unreacted (R)-esters in high yields and high enantiomeric purity. The influence of separation conditions on the efficiency and enantioselectivity of biocatalytic conversion was also studied. The reactions were carried out under normal conditions (stirring with a magnetic stirrer at room temperature) and microwave irradiation in the presence of hydrolases. Amano PS showed excellent selectivity and good yields in the hydrolysis of fluorinated aromatic compounds. The absolute configuration of the resulting compounds was based on biokinetic studies and the use of chiral HPLC. A molecular modeling of the kinetic resolution of carboxylic acid esters was carried out. Full article

An asymmetric synthesis is a favorable approach for obtaining enantiomerically pure substances, but racemic resolution remains an efficient strategy. This study aims to elucidate the chiral resolution of aromatic amino acids and their elution order using glycopeptides as chiral selectors through molecular docking analysis. Chiral separation experiments were conducted using Vancomycin as a chiral additive in the mobile phase (CMPA) at various concentrations, coupled with an achiral amino column as the stationary phase. The Autodock Vina 1.1.2 software was employed to perform molecular docking simulations between each enantiomer (ligand) and Vancomycin (receptor) to evaluate binding affinities, demonstrate enantiomeric resolution feasibility, and elucidate chiral recognition mechanisms. Utilizing Vancomycin as CMPA at a concentration of 1.5 mM enabled the separation of tryptophan enantiomers with a resolution of 3.98 and tyrosine enantiomers with a resolution of 2.97. However, a poor chiral resolution was observed for phenylalanine and phenylglycine. Molecular docking analysis was employed to elucidate the lack of separation and elution order for tryptophan and tyrosine enantiomers. By calculating the binding energy, docking results were found to be in good agreement with experimental findings, providing insights into the underlying mechanisms governing chiral recognition in this system and the interaction sites. This comprehensive approach clarifies the complex relationship between chiral discrimination and molecular architecture, offering valuable information for creating and improving chiral separation protocols. Full article

The subject of this study was to compare the enantioseparation of fourteen racemic esters that are liquid crystals. This study aimed to determine the difference in the enantioseparation of mixtures with protonated and fluorinated aliphatic chains and those with different orders of occurrence of benzene rings (benzoates and biphenylates). This research was carried out on two chiral polysaccharide columns: amylose tris(3-chloro-5-methylphenylcarbamate) (ReproSil Chiral MIG) and cellulose tris(3,5-dichlorophenylcarbamate) (ReproSil Chiral MIC). The columns were evaluated in HPLC separation. The analyses were performed in the normal- and reversed-phase systems. The mobile phase consisted of different solvent systems (acetonitrile/water and n-hexane/2-propanol) in different volume ratios to select optimal separation conditions. The main parameter evaluated in separating racemic mixtures was the resolution—Rs. All measurements were performed at 25 °C. The elution order was also determined. The highest value of resolution (over 11) and selectivity (over 3) was obtained for the ReproSil Chiral MIG column and the volume ratio of ACN:H₂O (95:5 v/v). Full article

Enantioseparation of nineteen liquid crystalline racemic mixtures obtained based on (R,S)-2-octanol was studied in reversed-phase mode on an amylose tris(3-chloro-5-methylphenylcarbamate) (ReproSil Chiral-MIG) and a cellulose tris(3,5-dichlorophenylcarbamate) (ReproSil Chiral-MIC). These polysaccharide-based chiral stationary phase (CSP) columns for High-Performance Liquid Chromatography (HPLC) were highly effective in recognizing isomers of minor structural differences. The mobile phase (MP), which consists of acetonitrile (ACN)/water (H₂O) at different volume ratios, was used. The mobile phases were pumped at a flow rate of 0.3, 0.5, or 1 mL·min⁻¹ with a column temperature of 25 °C, using a UV detector at 254 nm. The order of the elution was also determined. The chromatographic parameters, such as resolution (R_s), selectivity (α), and the number of theoretical plates, i.e., column efficiency (N), were determined. The polysaccharide-based CSP columns have unique advantages in separation technology, and this study has shown the potential usefulness of the CSP columns in separating liquid crystalline racemic mixtures belonging to the same homologous series. Full article

An enzyme-promoted addition of nitromethane to the appropriate phosphorylated imine (aza-Henry reaction) intended to be used in the synthesis of the title phosphoemeriamine, a phospha-analog of emeriamine (aminocarnitine), failed due to the tautomerization of the imine to the corresponding enamine. Nevertheless, both enantiomers of phosphoemeriamine were synthesized in high yield and enantiomeric purity using another chemoenzymatic approach, starting with a crucial step involving a CAL-B-mediated acetylation of the appropriate racemic precursor—diethyl 2-amino-3-dimethylaminopropylphosphonate—under kinetic resolution conditions. The enzymatic reaction was very efficient and provided each enantiomeric product in acceptable yield and with enantiomeric excess of 91 and 92%. The following appropriate chemical transformations led to the desired enantiomers of phosphoemeriamine in the form of phosphoemeriamine sesquichloride with enantiomeric excess up to 90%. Full article

(S)-Atenolol ((S)-2-(4-(2-Hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide) has been synthesized in >99% enantiomeric excess (ee) with the use of Candida antarctica lipase B from Syncozymes (Shanghai, China), in a kinetic resolution of the corresponding racemic chlorohydrin. A catalytic amount of base was used in deprotonation of the phenol building block. The enantiopurity of the chlorohydrin building block remained unchanged upon subsequent amination to yield the final drug. All four steps in the synthesis protocol have been optimized compared to previously reported methods, which makes this new protocol more sustainable and in accordance with green chemistry principles. The overall yield of (S)-atenolol was 9.9%, which will be further optimized. Full article

The molybdenum-catalyzed enantioselective ring-closing metathesis/kinetic resolution of a series of racemic planar-chiral 1,1′-diallylferrocene derivatives was reinvestigated utilizing the method of generating catalytically active chiral molybdenum-alkylidene species in situ, which allowed us to examine a variety of chiral molybdenum-alkylidene metathesis precatalysts in the present asymmetric reaction. With the catalyst screening experiments conducted in this study, the more practical reaction conditions, including a choice of a proper chiral molybdenum precatalyst, giving planar-chiral ferrocenes of higher enantiomeric purity and better chemoselectivity could be optimized. Full article

Chiral resolution is a technique of choice, making it possible to obtain asymmetric and enantiomerically pure compounds from a racemic mixture. This study investigated the behavior of vancomycin when used as a chiral additive in high-performance liquid chromatography (HPLC) to separate enantiomers of nonsteroidal anti-inflammatory drugs (NSAIDs), including ketoprofen, ibuprofen, flurbiprofen, and naproxen enantiomeric impurities. We compared two achiral stationary phases (C18 and NH₂) to assess the impact of mobile phase composition and stationary phase on the vancomycin retention time in the racemic resolution of drug enantiomers. Our results demonstrated the successful enantioseparation of all drugs using vancomycin in the mobile phase (phosphate buffer 0.05 M/2-propanol, 50/50) with an NH₂ column. This enhanced separation on the NH₂ column resulted from the chromatography system’s efficiency and vancomycin dimers’ stereoselective interaction on the NH₂ surface. This study underscores the importance of stationary phase selection in the chiral resolution of NSAIDs with vancomycin as a chiral additive. It offers valuable insights for future research and development of NSAID chiral separation methods, highlighting potential vancomycin applications in this context. Full article

Herein, we report the preparation of lipase immobilised on single-walled carbon nanotubes (SWCNTs) as an enantioselector for capillary monolithic columns and their application in the chiral separation of racemic pharmaceuticals. The columns were prepared through the encapsulation of functionalised SWCNTs (c-SWCNTs) within an organic monolithic polymer, followed by the immobilisation of lipase over the obtained monolith, over a three-day (L1) and five-day (L2) period. The prepared columns were tested for the enantioselective nano-HPLC separation of 50 racemic drugs. A suitable resolution was achieved for 25 drugs using nano-RP-HPLC conditions for both the L1 and L2 capillaries, while no specific resolution was detected under normal-phase HPLC conditions. The developed c-SWCNT-lipase-based polymeric monolithic capillaries are a promising expansion for separating pharmaceutical enantiomers’ using nano-HPLC. Full article

Unknown N-acylated amino acid (N-AAA) conjugates have been detected in maple syrup urine disease (MSUD) and other inborn errors of metabolism (IEMs). This study aimed to elucidate the mechanism behind the formation of urinary N-AAA conjugates. Liquid–liquid extraction was employed to determine the enantiomeric composition of N-AAA conjugates, followed by liberation of conjugated amino acids through acid hydrolysis. Gas chromatography–mass spectrometry (GC–MS) was used to separate amino acid enantiomers. In vitro experiments were conducted to test the non-enzymatic formation of N-AAA conjugates from 2-keto acids and ammonia, with molecular modelling used to assess possible reaction mechanisms. Adequate amounts of N-AAA conjugates were obtained via organic acid extraction without concurrent extraction of native amino acids, and hydrolysis was complete without significant racemisation. GC–MS analysis successfully distinguished amino acid enantiomers, with some limitations observed for L-isoleucine and D-alloisoleucine. Furthermore, investigation of racemic N-AAA conjugates from an MSUD case confirmed its non-enzymatic origin. These findings highlight the value of employing chiral strategy and molecular modelling to investigate the origin of unknown constituents in biological samples. Additionally, these conjugates warrant further investigation as potential factors contributing to MSUD and other IEMs. Full article

An easy and versatile method was designed and applied successfully to obtain access to lipase-based cross-linked-enzyme aggregate-like copolymers (CLEA-LCs) using one-pot, consecutive cross-linking steps using two types of homobifunctional cross-linkers (glutaraldehyde and putrescine), mediated with amine activation through pH alteration (pH jump) as a key step in the process. Six lipases were utilised in order to assess the effectiveness of the technique, in terms of immobilization yields, hydrolytic activities, thermal stability and application in kinetic resolution. A good retention of catalytic properties was found for all cases, together with an important thermal and storage stability improvement. Particularly, the CLEA-LCs derived from Candida rugosa lipase showed an outstanding behaviour in terms of thermostability and capability for catalysing the enantioselective hydrolysis of racemic ibuprofen ethyl ester, furnishing the eutomer (S)-ibuprofen with very high conversion and enantioselectivity. Full article