STUDY OF BIOLOGICAL ACTIVITY OF RACEMIC AND OPTICALLY ACTIVE ESTERS OF NAPHTHENIC AND FATTY ACIDS BASED ON UNSATURATED OXYESTERS

Petrochemical products based on petroleum naphthenic acids have special properties. Esters of naphthenic acids possess practically valuable organic compounds. The aim of this work is the development of effective methods for the preparation of aromatic esters based on naphthenic and individual fatty acids which is a very promising direction in the medicine practice. The synthesis of unsaturated racemic and chiral oxyethers was carried out on the basis of the interaction of chloromethylpropargyl (allyl) esters with carbonyl compounds with the participation of metallic zinc. Also, to study the biological activity, racemic and optically active esters were synthesized based on naphthenic acids and unsaturated racemic and chiral oxyesters. As test cultures used: gram-positive (Staphylo-coccus aureus-Staphylococcus aureus), gram-negative (Pseudomonas aeruginosa – Pseu-domonas aeruginosa, Escherichia coli) bacteria, as well as yeast-like fungi of the genus Candida - Candida albicans. Analysis of the biological activity of the synthesized compounds showed that optically active bicyclo [2.2.1] hept-5-ene-2-methylol monoesters have higher antimicrobial and antifungal activity compared to their racemic analogs and drugs used in medicine.

Semisynthetic Derivatives of Selected Amaryllidaceae Alkaloids as a New Class of Antimycobacterial Agents

The search for novel antimycobacterial drugs is a matter of urgency, since tuberculosis is still one of the top ten causes of death from a single infectious agent, killing more than 1.4 million people worldwide each year. Nine Amaryllidaceae alkaloids (AAs) of various structural types have been screened for their antimycobacterial activity. Unfortunately, all were considered inactive, and thus a pilot series of aromatic esters of galanthamine, 3-O-methylpancracine, vittatine and maritidine were synthesized to increase biological activity. The semisynthetic derivatives of AAs were screened for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Ra and two other mycobacterial strains (M. aurum, M. smegmatis) using a modified Microplate Alamar Blue Assay. The most active compounds were also studied for their in vitro hepatotoxicity on the hepatocellular carcinoma cell line HepG2. In general, the derivatization of the original AAs was associated with a significant increase in antimycobacterial activity. Several pilot derivatives were identified as compounds with micromolar MICs against M. tuberculosis H37Ra. Two derivatives of galanthamine, 1i and 1r, were selected for further structure optimalization to increase the selectivity index.

Ohmic heating for polyphenol extraction from grape berries: an innovative prefermentary process

High energy consumption is often required to increase the extraction of phenolic compounds from grapes during alcoholic fermentation. Processes such as thermovinification require significant temperature changes over a long period of time to ensure the diffusion of phenolic compounds from the grape skin layer to the must. In this study, the capability of the ohmic heating (OH) process (E = 55 V/cm, t = 60–90 s, T = 72 °C) to improve the extractability of valuable intracellular compounds from grape skins of Aglianico and Barbera grape matrices before the alcoholic fermentation stepAs similarly reported by Donsì et al. (2010), any tissue damage to grape skins occurring after the application of either conventional or ohmic heating was not found to influence the rate of fermentation. was investigated and compared with both untreated and conventional thermally (CH) treated (T = 72 °C, t = 90 s) samples. Total phenolics and antioxidant capacity were monitored during fermentation (10 days). In comparison to the conventional thermal treatment, the results showed that the phenolic compound content of musts was twice as high immediately after OH treatment. This process could drastically improve the classic prefermentary maceration (thermovinifications, cold macerations, etc.) time. In finished wines produced from the treated musts, the total polyphenolic content of OH wines was up to 17 % higher than that of CH wines, and 30 % higher than that of untreated wines. No differences in concentrations of total tannins and anthocyanins were observed between conventional and ohmic heated musts. However, an increase of 30 to 200 % for some aromatic esters was observed in wines from ohmic heated musts. Overall, the outcomes of this work proved that, in addition to the thermal effect, the moderate electric field (MEF) applied during ohmic heating has the potential to induce an instantaneous release of polyphenolic compounds due to the electroporation phenomenon of cell membranes, thus saving energy and reducing processing time.

DEVELOPMENT AND VALIDATION OF AN ANALYTICAL METHOD FOR CONDENSED TANNIN EXTRACTS OBTAINED FROM THE BARK OF FOUR TREE SPECIES USING HPLC

Herein, we evaluated the content of condensed tannins present in the bark of four tree species that are Quercus laurina Humb. & Bonpl., Quercus crassifolia Humb. & Bonpl., Arbutus xalapensis Kunth, and Prunus serotina Ehrn. An analytical method using high-performance liquid chromatography (HPLC) for condensed tannin extracts was developed and validated. Also, the aqueous extracts were analyzed by Fourier transform infrared spectroscopy (FTIR). Based on the Stiasny number, A. xalapensis, and Q. laurina represent an important source of condensed tannins, which may be subject to exploitation. Using infrared spectroscopy, it was observed that tannins do not show an important signal of carbonyl groups (aromatic esters) with respect to high purity catechin. Furthermore, the band of the hydroxyl group is less pronounced in tannins, because various hydroxyl are interacting with each other. However, it can be seen that the method of extraction of wood tannins developed in this work, presents satisfactory results.

Ni-Catalyzed Aryl Sulfide Synthesis through an Aryl Exchange Reaction

A Ni-catalyzed aryl sulfide synthesis through an aryl exchange reaction between aryl sulfides and a variety of aryl electrophiles was developed. By using 2-pyridyl sulfide as a sulfide donor, this reaction achieved the synthesis of aryl sulfides without using odorous and toxic thiols. The use of a Ni/dcypt catalyst capable of cleaving and forming aryl–S bonds was important for the aryl exchange reaction between 2-pyridyl sulfides and aryl electrophiles, which include aromatic esters, arenol derivatives, and aryl halides. Mechanistic studies revealed that Ni/dcypt can simultaneously undergo oxidative additions of aryl sulfides and aromatic esters, followed by ligand exchange between the generated aryl–Ni–SR and aryl–Ni–OAr species to furnish aryl exchanged compounds.

Ni-Catalyzed Aryl Sulfide Synthesis through an Aryl Exchange Reaction

A Ni-catalyzed aryl sulfide synthesis through an aryl exchange reaction between aryl sulfides and a variety of aryl electrophiles was developed. By using 2-pyridyl sulfide as a sulfide donor, this reaction achieved the synthesis of aryl sulfides without using odorous and toxic thiols. The use of a Ni/dcypt catalyst capable of cleaving and forming aryl–S bonds was important for the aryl exchange reaction between 2-pyridyl sulfides and aryl electrophiles, which include aromatic esters, arenol derivatives, and aryl halides. Mechanistic studies revealed that Ni/dcypt can simultaneously undergo oxidative additions of aryl sulfides and aromatic esters, followed by ligand exchange between the generated aryl–Ni–SR and aryl–Ni–OAr species to furnish aryl exchanged compounds.

The Theoretical Total Synthesis of an Aromatic Esters of the Crinane Amaryllidaceae Alkaloid Ambelline

ABSTRACT. A series of crinane-type alkaloid ambelline derivatives were assessed for their potency to inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), which has been shown to be effective medicine for the treatment of Alzheimer’s disease. However, no enzyme modification has been reported total synthesis. In this work, two possible theoretical synthesis paths of Crinane-type alkaloid ambelline were discussed in this article. The major difficulty of the proposed synthesis was the synthesis of the quaternary carbon. One of the approaches emphasized on the reactions between cyclic and heterocyclic compounds and substrates on the intermediates to generate the quaternary carbon shown on the desired product. The other approach utilized series of amine reactions and Michael addition to create the precursor for the reactant in the Diels-Alder reaction and, therefore, the quaternary carbon, and finally, the desired natural product was obtained after a weak acid workup. The synthesis of ambelline has the potential to provide new pathways for treatment of Alzheimer’s disease.

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.

Enological Repercussions of Non-Saccharomyces Species 2.0

Non-Saccharomyces yeast species are currently a biotechnology trend in enology and broadly used to improve the sensory profile of wines because they affect aroma, color, and mouthfeel. They have become a powerful biotool to modulate the influence of global warming on grape varieties, helping to maintain the acidity, decrease the alcoholic degree, stabilize wine color, and increase freshness. In cool climates, some non-Saccharomyces can promote demalication or color stability by the formation of stable derived pigments. Additionally, non-Saccharomyces yeasts open new possibilities in biocontrol for removing spoilage yeast and bacteria or molds that can produce and release mycotoxins, and therefore, can help in reducing SO2 levels. The promising species Hanseniaspora vineae is analyzed in depth in this Special Issue in two articles, one concerning the glycolytic and fermentative metabolisms and its positive role and sensory impact by the production of aromatic esters and lysis products during fermentation are also assessed.

Repurposing chloramphenicol acetyltransferase for a robust and efficient designer ester biosynthesis platform

Robust and efficient enzymes are essential modules for metabolic engineering and synthetic biology strategies across biological systems to engineer whole-cell biocatalysts. By condensing an acyl-CoA and an alcohol, alcohol acyltransferases (AATs) can serve as an interchangeable metabolic module for microbial biosynthesis of a diverse class of ester molecules with broad applications as flavors, fragrances, solvents, and drop-in biofuels. However, the current lack of robust and efficient AATs significantly limits their compatibility with heterologous precursor pathways and microbial hosts. Through bioprospecting and rational protein engineering, we identified and repurposed chloramphenicol acetyltransferases (CATs) from mesophilic prokaryotes to function as robust and efficient AATs compatible with at least 21 alcohol and 8 acyl-CoA substrates for microbial biosynthesis of linear, branched, saturated, unsaturated and/or aromatic esters. By plugging the best engineered CAT (CATec3 Y20F) into the gram-negative mesophilic bacterium Escherichia coli, we demonstrated that the recombinant strain could effectively convert various alcohols into desirable esters, for instance, achieving a titer of 13.9 g/L isoamyl acetate with 95% conversion by fed-batch fermentation. The recombinant E. coli was also capable of simulating the ester profile of roses with high conversion (> 97%) and titer (> 1 g/L) from fermentable sugars at 37°C. Likewise, a recombinant gram-positive, cellulolytic, thermophilic bacterium Clostridium thermocellum harboring CATec3 Y20F could produce many of these esters from recalcitrant cellulosic biomass at elevated temperatures (>50°C) due to the engineered enzyme’s remarkable thermostability. Overall, the engineered CATs can serve as a robust and efficient platform for designer ester biosynthesis from renewable and sustainable feedstocks.