Sugar Esters Research Articles

Gas chromatography-mass spectrometry (GC-MS) profiling reveals substantial metabolome diversity in seabuckthorn (Hippophae rhamnoides L.) berries originating from different geographical regions in the Indian Himalayas.

Seabuckthorn (Hippophae rhamnoides L.) is a high-altitude plant with immense medicinal, nutritional, and therapeutic value. Earlier studies have documented the presence of various useful bioactive substances in this species; however, comprehensive metabolome profiling of seabuckthorn berries originating from different regions of the Indian Himalayas has not been undertaken. Metabolomic profiling of seabuckthorn berries originating from different geographical sites in the Himachal Pradesh and Jammu & Kashmir regions of the Indian Himalayas was performed by using gas chromatography-mass spectrometry. The GC-MS metabolome profiles of seabuckthorn berries collected from different sites (altitude 1,400-4,270 m; average temperature 8°C-27°C) were subjected to multivariate analysis following principal component analysis and hierarchical clustering analysis. The GC-MS results showed substantial variability for berry metabolites, including fatty acids, alkyl ethers, and alkyl esters. Fatty acids and their esters were mainly responsible for the variation in the berry metabolome. The metabolite expression profile heat map revealed two distinct groups of seabuckthorn berries originating from Himachal Pradesh (Lahaul and Spiti) and Jammu & Kashmir (Leh, Nubra, and Kargil), the former showing higher expression of metabolites. Interestingly, a strong negative association existed between altitude and the amounts of metabolites such as amides, alkyl esters, alcohols, sugars, and sugar esters. In contrast, temperature showed a strong positive association with ketone and alkyl ether levels. GC-MS profiling provides important phytochemical indicators to distinguish between seabuckthorn berries from different geographical sites. Our metabolome profiling analysis generated valuable information that will be useful in the formulation of various seabuckthorn products, benefiting farmers and industries.

Development of organogel-based emulsions to enhance the loading and bioaccessibility of 5-demethylnobiletin

5-Demethylnobiletin (5-DMN), identified in the aged citrus peels, has received increasing attentions due to its outstanding bioactivity among citrus polymethoxyflavones (PMFs). However, the poor water solubility and high crystallinity limit its oral bioavailability. Besides, the solubility of 5-DMN in the oil is very limited, which restricts its loading capacity in emulsions for bioavailability enhancement. In this study, an organogel formulation was developed to improve the solubility of 5-DMN in medium-chain triacylglycerols by 3.5 times higher without crystal formation during 5-day storage at room temperature. Increasing the gelator (i.e., sugar ester) concentration led to the increase of viscosity and a gel-like structure of the organogel. The ternary phase diagram of organogel-based emulsions was explored, and 40% organogel was selected as the oil phase for emulsion preparation. Increasing the concentration of Tween 80 from 0% to 6% decreased the droplet size and viscoelasticity of the emulsions. Two in vitro models, the pH-stat lipolysis model and TNO gastro-intestinal model (TIM-1), were applied to investigate the bioaccessibility of 5-DMN in different delivery systems. Compared with the conventional emulsion and oil suspension, the pH-stat lipolysis demonstrated that the organogel-based emulsion was the most efficient tool to enhance 5-DMN bioacccessibility. Moreover, TIM-1 digestive study indicated that 5-DMN bioaccessibility delivered by organogel-based emulsions was about 3.26-fold higher than that of oil suspension. Our results suggested that the organogel-based emulsion was an effective delivery route to enhance the loading and bioaccessibility of lipophilic compounds of high crystallinity.

In Search of Effective Anticancer Agents-Novel Sugar Esters Based on Polyhydroxyalkanoate Monomers.

Cancer is one of the deadliest illness globally. Searching for new solutions in cancer treatments is essential because commonly used mixed, targeted and personalized therapies are sometimes not sufficient or are too expensive for common patients. Sugar fatty acid esters (SFAEs) are already well-known as promising candidates for an alternative medical tool. The manuscript brings the reader closer to methods of obtaining various SFAEs using combined biological, chemical and enzymatic methods. It presents how modification of SFAE’s hydrophobic chains can influence their cytotoxicity against human skin melanoma and prostate cancer cell lines. The compound’s cytotoxicity was determined by an MTT assay, which followed an assessment of SFAEs’ potential metastatic properties in concentrations below IC50 values. Despite relatively high IC50 values (63.3–1737.6 μM) of the newly synthesized SFAE, they can compete with other sugar esters already described in the literature. The chosen bioactives caused low polymerization of microtubules and the depolymerization of actin filaments in nontoxic levels, which suggest an apoptotic rather than metastatic process. Altogether, cancer cells showed no propensity for metastasis after treating them with SFAE. They confirmed that lactose-based compounds seem the most promising surfactants among tested sugar esters. This manuscript creates a benchmark for creation of novel anticancer agents based on 3-hydroxylated fatty acids of bacterial origin.

Lipozyme 435-Mediated Synthesis of Xylose Oleate in Methyl Ethyl Ketone.

In this paper, we have performed the Lipozyme 435-catalyzed synthesis of xylose oleate in methyl ethyl ketone (MEK) from xylose and oleic acid. The effects of substrates’ molar ratios, reaction temperature, reaction time on esterification rates, and Lipozyme 435 reuse were studied. Results showed that an excess of oleic acid (xylose: oleic acid molar ratio of 1:5) significantly favored the reaction, yielding 98% of xylose conversion and 31% oleic acid conversion after 24 h-reaction (mainly to xylose mono- and dioleate, as confirmed by mass spectrometry). The highest Lipozyme 435 activities occurred between 55 and 70 °C. The predicted Ping Pong Bi Bi kinetic model fitted very well to the experimental data and there was no evidence of inhibitions in the range assessed. The reaction product was purified and presented an emulsion capacity close to that of a commercial sugar ester detergent. Finally, the repeated use of Lipozyme 435 showed a reduction in the reaction yields (by 48 and 19% in the xylose and oleic acid conversions, respectively), after ten 12 h-cycles.

Effect of administration of rice bran oil emulsion beverages on tumor necrosis factor-alpha (TNF-α) level

Rice bran oil emulsion beverage is a functional food rich in antioxidants and beneficial for human health, particularly to prevent metabolic syndrome.Metabolic syndrome is defined by a waist circumference of > 90 cm and two additional criteria out of five, namely triglycerides (TG) > 150 mg/dL, HDL-C < 40 mg/dL, and/or 140/90 mmHg, blood pressure,and fasting blood sugar of 100 mg / dL.This research aimed to examine the level of tumor necrosis factor-α (TNF-α) after the intervention of taking rice bran emulsion and determine the parameter shifted on metabolic syndrome. This study was a parallel-group, double-blind study with randomized controlled trials. The subjects were divided into two groups: treatment and control. The first group (n=19) received two glasses of rice bran emulsion per day for four weeks, while the control group (n=17) received two glasses of placebo per day for four weeks. Different intakes of fat, iron, and vitamin B1were present in the control group before and after the intervention (p=0.05). The data were analyzed using independent T-test samples against differences for each group from before and after interventions. The formulation of rice bran emulsion was prepared using bran oil, water, sugar ester, CMC, sucralose, salt, and flavor. The study demonstrated that TNF-α levels in both groups decreased from 6.8 ± 7.3 to 4.7 ± 0.6 (pg/dL)but were not significant (p>0.05). Nutrition changes influenced the intakes of fat, iron,and vitamin B1but did not influence metabolic syndrome parameters of the treatment group. The level of nutritional adequacy-fat, iron and vitamin B1 pre-and post-intervention in both groups were significantly different. In conclusion, the levels of serum TNF-α on the treatment group had a decrease than those in the control group; however, it is not significant. Further study needs to be done to verify this finding.

<i>In Silico</i> Biological Profile Prediction of Some Selectively Synthesized Acyl Rhamnopyranosides

Over the past several decades significant biological activities including brains protective and antimicrobial activities have made sugar esters (SEs) as a topic of great interest. In this context, unimolar 3-chlorobenzoylation of methyl α-L-rhamnopyranoside (4) using dibutyltin oxide method regioselectively furnished only the 3-O-substitution product 5 in excellent yield. The reaction proceeded via the formation of a cyclic 2,3-O-dibutylstannylene intermediate where equatorial hydroxyl group is activated by the tin atom leading to the formation of product 5 only. To get biologically important rhamnopyranoside esters chlorobenzoate 5 was further converted into three newer 2,4-di-O-acyl products 6-9 with other acylating agents using direct acylation method. Prediction of activity spectra for substances (PASS) indicated that these rhamnopyranoside esters have many promising biological profiles including CYP2H substrate, membrane permeability inhibitor and better antifungal activities. Additionally, ADMET and drug likeness properties of SEs 5-8 were predicted and discussed.

Kinetic stability of the oil-in-water emulsions and dynamic interfacial properties of mixtures of sucrose esters and polysaccharides

This article presents a study of the interfacial properties of oil-in-water emulsions containing sugar esters and polysaccharides. Sucrose fatty acid esters were synthesized using immobilized Candida antarctica lipase B. A yield of 53.4% was obtained using 2-methyl-2-butanol and 1:3 M ratio of sucrose:stearic acid. Equilibrium surface tension was 45 mN/m and low critical micellar concentration (CMC) value was obtained (ca. 10 mg/mL), characteristic of non-ionic surfactant. The interfacial properties of mixtures of sucrose esters and polysaccharides, at the oil–water interface were determined using a pendant drop tensiometer. Addition of polysaccharides increased the interfacial tension. Studies of interfacial viscoelasticity showed that the films were predominantly elastic. The presence of polysaccharides in emulsions resulted in flocculated droplets. All the emulsions presented great stability along 28 days with no creaming formation.

Direct esterification of sucrose: novel lead-compounds against cancer

Introduction Phenylpropanoic sugar esters are a class of naturally occurring active substances, mainly found in ancient oriental medicinal plants (Figure 1), with a scope of activity ranging from antioxidant, antibacterial as well as anti-tumoral [1]. Though relatively simple in structure – owing to their resemblance to natural carbohydrates - few have been the successful attempts to obtain them in the laboratory, hampered mainly by the fact that the high similarity between functional groups in sugars restrains the feasibility of current methods and their reproducibility in industrial scales [2]. Our study aims for the development of reliable and effective methods for the synthesis of a library of phenylpropanoic esters derived from sucrose. Figure 1. Veronicastrum Sibiricum, one of the plants containing phenylpropanoic sucrose esters as the active substance. Materials and methods The lead-compounds are obtained by treating sucrose with a vigorous basic medium. The preferential esterification in the sugar hydroxyls is catalysed by a metal halide salt. The different compounds obtained are meant to be tested and screened for their biological applications, with particular emphasis on their action against cancer cells. Results Our most appealing discovery is the possibility of directly enhancing the regioselectivity of the 2, 3′, 6 and 6′-hydroxyl positions in the sugar moiety induced by transition-metal salts as catalysts [3] (Scheme 1). Different metal salts induce the different hydroxyls mentioned for a direct esterification with the acylating agent, which reflects the specificity and versatility of this novel class of reactions. Scheme 1. General route for the metal-chelate direct esterification of sucrose molecule. Discussion and conclusions We can conclude, so far, that cobalt and copper chloride salts give the best results in terms of yield (more than 30% conversion) and decreased reaction time (less than one hour). To further extend our knowledge about the metal-chelate directed acylation method, we are also experimenting with other halide salts, namely zinc, calcium, nickel and iron, as well as with derivatized molecules of sucrose. Thus, our work can certainly lead the development of novel drugs and resourceful cancer therapies.

Methyl 4-O-(2-chlorobenzoyl)-α-L-rhamnopyranosides: Synthesis, Characterization, and Thermodynamic Studies

Sugar esters (SEs) with promising antimicrobial functionality were found to be a better choice to solve the multidrug resistant (MDR) pathogens due to their improved antimicrobial efficacy, and drug-likeness properties. In this context, 2-chlorobenzoyl ester group at C-4 position of methyl α-L-rhamnopyranoside was prepared via 2,3-O-acetonide protection followed by unimolar 2-chlorobenzoylation, and acetonide deprotection. The selective 4-O-(2-chlorobenzoyl)-α-L-rhamnopyranoside, thus formed, was converted into five 2,3-di-O-acyl esters with different aliphatic, and sulphonyl chains to obtain biologically important novel rhamnopyranoside-based SEs. All the synthesized compounds were optimized employing density functional theory (DFT). Thermodynamic calculations including frontier molecular orbital, and molecular electrostatic potential (MEP) were calculated and discussed. Attachment of multiple ester groups enhanced their stability, reactivity, and softness indicating their more polar and reactive nature than the non-ester sugars. Corroboration of all these properties might be helpful for their interactions with several enzymes (proteins) during different biological activities. The present study also revealed that incorporation of 2-chlorobenzoyl and mesyl groups in rhamnopyranoside skeleton increased better thermodynamic properties. DOI: http://dx.doi.org/10.17807/orbital.v13i1.1532

Process for continuous production of sugar esters of medium-chain fatty acid: Effect of residence time on productivity and scale-up design

Continuous production of the sugar ester (SEs) of a medium-chain fatty acid was conducted in a column reactor packed with a strongly basic anion-exchange resin and its production behavior was compared with that of a conventional long-chain fatty acid SE. Using the resin catalyst under mild conditions (60 °C and atmospheric pressure) facilitated continuous production of the medium-chain fatty acid SE in almost 60% yield, even with a short residence time of 8 min. The productivity per unit time and total output before resin deactivation were determined as scale-up parameters. Both values were five times higher for medium-chain fatty acid SE production compared with long-chain fatty acid SE production. Based on these values, the required amount of the resin can be estimated according to the desired production volume. Furthermore, the resin catalyst activity decreased gradually during continuous production, but repeated resin use was achieved with periodic regeneration. • A continuous production of medium-chain sugar ester was conducted using a resin catalyst. • With a short residence time of around 8 min, product yield of almost 60% was achieved. • As scale-up parameters for apparatus design, productivity and total output were determined. • The resin catalyst was verified to be reusable through periodic regeneration treatment.

Caffeic Acid and Its Derivatives: Antimicrobial Drugs toward Microbial Pathogens.

Caffeic acid is a plant-derived compound that is classified as hydroxycinnamic acid which contains both phenolic and acrylic functional groups. Caffeic acid has been greatly employed as an alternative strategy to combat microbial pathogenesis and chronic infection induced by microbes such as bacteria, fungi, and viruses. Similarly, several derivatives of caffeic acid such as sugar esters, organic esters, glycosides, and amides have been chemically synthesized or naturally isolated as potential antimicrobial agents. To overcome the issue of water insolubility and poor stability, caffeic acid and its derivative have been utilized either in conjugation with other bioactive molecules or in nanoformulation. Besides, caffeic acid and its derivatives have also been applied in combination with antibiotics or photoirradiation to achieve a synergistic mode of action. The present review describes the antimicrobial roles of caffeic acid and its derivatives exploited either in free form or in combination or in nanoformulation to kill a diverse range of microbial pathogens along with their mode of action. The chemistry employed for the synthesis of the caffeic acid derivatives has been discussed in detail as well.

A novel maltoheptaose-based sugar ester having excellent emulsifying properties and optimization of its lipase-catalyzed synthesis

A novel maltoheptaose-palmitate ester (G7-PA) was synthesized and investigated for emulsion properties. First of all, the optimal conditions for lipase-catalyzed G7-PA synthesis, which were 0.2 of the G7/PA molar ratio, 33.5 U of immobilized CALB per 1 g of PA in 10% DMSO, were determined by response surface methodology. G7-PA was compared with the commercial sucrose-PA (S-PA) in terms of emulsion-forming ability and stability at extreme conditions. At the 0.1% surfactant concentration, G7-PA emulsion exhibited a droplet distribution similar to the 0.2% surfactant condition, while S-PA emulsion was quickly destabilized. G7-PA showed better emulsifying properties than the S-PA at the acidic condition (pH 3). Flocculation and phase separation was observed at the S-PA emulsion, but the G7-PA emulsion was stable for 7-day. In thermostability tests, G7-PA and S-PA both were stable up to the boiling temperature. Conclusively, G7-PA exhibits excellent properties as a biosurfactant in O/W emulsion compared with S-PA.

Efficient Acylation of Sugars and Oligosaccharides in Aqueous Environment Using Engineered Acyltransferases

A major challenge for the enzymatic synthesis of sugar esters is the low solubility of sugars in anhydrous, often toxic, organic solvents. We overcame this limitation by using acyltransferases for ...

Glucopyranoside Dipentanoyl Esters: Synthesis, PASS Predication, Antimicrobial and <i>In Silico</i> ADMET Studies

Dimolar pentanoylation of methyl α-D-glucopyranoside using direct method furnished the 2,6-di-O-pentanoate indicating regioselectivity at C-6 and C-2 positions. To develop glucopyranoside based potential antimicrobial agents, 2,6-di-O-pentanoate was further converted into eight newer 3,4-di-O-acyl esters reasonably in good yields. Both prediction of activity spectra for substances (PASS) and in vitro antimicrobial activity test established them as better antifungals than antibacterials. PASS predication also indicated that these sugar esters (SEs) are more potent as anticarcinogenic agents than as antioxidant agents. Structure activity relationship along with in silico ADMET studies clearly indicated that combination of pentanoyl (C5) and lauroyl (C12) in the glucopyranoside framework could be a potential antifungal agent especially against Macrophomina phaseolina.

Research on the Manufacture of Moringa Milky Tea

In this research, moringa, black tea, milk powder, white sugar and sucrose ester were used as raw materials, and the optimal processing technology of moringa milky tea was studied by single factor and orthogonal experiments. These results showed that the optimal formula for moringa milky tea was: 7:8 of ratio of tea liquor (black tea liquor: moringa liquor), 11% of milk powder, 4% of white sugar and 0.9% of sucrose ester. Moreover, the milky tea processed with this formula has a strong milk flavor, a delicate and soft taste.

Enzymatic Synthesis of Glucose‐ and Xylose Laurate Esters Using Different Acyl Donors, Higher Substrate Concentrations, and Membrane Assisted Solvent Recovery

AbstractGlucose‐ and xylose laurate esters are enzymatically synthesized using equimolar substrate concentrations in 2‐methyl‐2‐butanol, comparing free lauric acid with methyl‐ and vinyl‐laurate as acyl donors. All reactions result in ≥70% acyl donor conversions after 72 h but the activated donors are also partially hydrolyzed to lauric acid, highlighting the difficulty in controlling water presence in this particular reaction system. The esterification of xylose generates a complex product profile, with several regioisomers of monoesters and diesters. The esterification of glucose is quite selective, forming mainly the 6‐O monoester (≥96%) with a small presence of two diester isomers (4%). Increasing substrate concentration up to 800 millimoles kg−1 results in lower conversion values (down to 58%) but shows that the reaction proceeds successfully even in the presence of high amounts of insoluble glucose. However, the reaction is less selective and the proportion of diester increases, becoming up to 46% (molar fraction) of the final product. Solvent recovery after esterification can be achieved by organic solvent nanofiltration through a polymeric membrane able to retain ≥80% of all reaction substrates and products.Practical Applications: The use of high substrate concentrations during the enzymatic synthesis of sugar ester biosurfactants leads to product titers that are more industrially appealing, without the need to find a solvent that can solubilize all initial substrate. The sustainability of the enzymatic conversion at mild temperatures can be enhanced by recycling of the reaction solvent through organic solvent nanofiltration, an energy efficient alternative to other traditional methods like distillation.

Chemoenzymatic Synthesis of New Aromatic Esters of Mono- and Oligosaccharides

An efficient and convenient chemoenzymatic route for the synthesis of novel phenolic mono-, di- and oligosaccharide esters is described. Acetal derivatives of glucose, sucrose, lactose and inulin were obtained by chemical synthesis. The fully characterized pure sugar acetals were subjected to enzymatic esterification with 3-(4-hydroxyphenyl) propionic acid (HPPA) in the presence of Novozyme 435 lipase as a biocatalyst. The aromatic esters of alkyl glycosides and glucose acetal were obtained with good esterification yields, characterized by mass spectrometry (MALDI-TOF MS), infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (1H NMR, 13C NMR). The synthesis of aromatic esters of disaccharide acetals was successful only for the enzymatic esterification of sucrose acetal. The new chemoenzymatic route allowed the synthesis of novel aromatic esters of inulin as the inulin monoacetal monoester and diester and the inulin diacetal monoester with a polymerization degree of two, as well as the inulin monoacetal monoester with a degree of polymerization of three, were obtained by enzymatic acylation of inulin acetals with HPPA. These compounds could represent a new class of sugar ester surfactants with enhanced bioactivity, antioxidative and antimicrobial properties and with potential application in drug delivery systems.

Synthesis, PASS Predication, Antimicrobial, DFT, and ADMET Studies of Some Novel Mannopyranoside Esters

Due to the biodegradability and drug-likeness properties sugar esters (SEs) are getting especial attention to the synthetic and bioorganic chemists. In this context, we have synthesized several 6-O-pentanoyl mannopyranoside esters (5-9) with alkanoyl and sylfonyl chains reasonably in good yields. Both the prediction of activity spectra for substances (PASS) and in vitro tests indicated that these mannopyranoside esters possess better potentiality against fungal pathogens than the bacterial organisms. These SEs were also optimized with quantum chemical density functional theory (DFT), and various thermodynamic properties like frontier molecular orbital, and molecular electrostatic potential (MEP) were calculated and discussed. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) calculations indicated that these SEs can pass through blood brain barrier and less toxic. Drug-likeness results indicated good conditions for alkanoyl esters rather than sulfonyl esters despite their promising antifungal results. All the in vitro and in silico results indicated that the combination of pentanoyl (C5) and lauroyl (C12) chains in mannopyranoside framework, as in 9, might be a potential candidate for novel antifungal agent.

Thioglycoligase derived from fungal GH3 \u03b2-xylosidase is a multi-glycoligase with broad acceptor tolerance

The synthesis of customized glycoconjugates constitutes a major goal for biocatalysis. To this end, engineered glycosidases have received great attention and, among them, thioglycoligases have proved useful to connect carbohydrates to non-sugar acceptors. However, hitherto the scope of these biocatalysts was considered limited to strong nucleophilic acceptors. Based on the particularities of the GH3 glycosidase family active site, we hypothesized that converting a suitable member into a thioglycoligase could boost the acceptor range. Herein we show the engineering of an acidophilic fungal β-xylosidase into a thioglycoligase with broad acceptor promiscuity. The mutant enzyme displays the ability to form O-, N-, S- and Se- glycosides together with sugar esters and phosphoesters with conversion yields from moderate to high. Analyses also indicate that the pKa of the target compound was the main factor to determine its suitability as glycosylation acceptor. These results expand on the glycoconjugate portfolio attainable through biocatalysis.

Controlling reaction selectivity for sugar fatty acid ester synthesis by using resins with different basicities

A strongly basic ion-exchange resin catalyst was reported to exhibit a high catalytic activity in transesterification to produce a bio-based surfactant, sugar ester under mild condition. However, the side-reactions to decompose the reactant and the product were found to occur. This study was aimed to improve the selectivity of sugar ester synthesis by newly focusing on the basicity of the resin. A weakly basic resin (Diaion WA20) with a lower mass transfer resistance suppressed the decompositions while maintaining synthesis rate. Controlling molar ratio of the reactants in the intraparticle reaction field also increased the reaction selectivity, 72.1% and product yield, 57.5%. Both values were drastically increased compared to the reported values with the strongly basic resin (selectivity 50.9%, yield 14.3%). This is the first knowledge to show a high catalytic activity of weakly basic resin. These results suggest that a more efficient continuous production process would be possible.