Chemo- and regio-selective enzymatic lipophilisation of rutin, and physicochemical and antioxidant properties of rutin ester derivatives.

Enzymes are one of the most powerful tools in organic Green Chemistry and enzymatic reactions offer numerous advantages like regio- and enantio-selectivity along with their eco-friendly and sustainable nature. More specifically, lipases can catalyse both ester hydrolysis and formation depending on the nature of the substrate and water content. Herein, the focus is on the development of an enzymatically catalysed lipophilisation of natural compounds using lipases of microbial origin and the investigation of the optimal reaction conditions, aiming ultimately to ameliorate the compounds' properties. The flavonoid disaccharide rutin (quercetin-3-O-rutinoside) was the model compound on which the acylation protocol was built, allowing an efficient procedure to be established, while simultaneously offering the possibility of developing rapid, clear and robust methodologies, using state-of-the-art techniques, for analysis and purification of the synthesized compounds. An optimal 72 h reaction at 55 °C, using Candida antarctica lipase B immobilized on acrylic resin, combined with silicon dioxide as dehydrating agent, followed by product purification, achieved conversion ratios up to 50%. Full characterization and evaluation of the physicochemical and antioxidant properties of the esterified compounds was obtained. The lipophilicity of the rutin esters produced increased with increasing alkyl chain length, yet antioxidant properties were unaffected in comparison with the parent compound. A preparatively useful acylation protocol was established, allowing full investigation into the properties of the acylated compounds. It is also applicable for use on mixtures of compounds as most natural products are found in nature in mixtures and such a development greatly enhances the potential of this method for future commercial applications.

Green extraction of polyphenols from citrus peel by-products and their antifungal activity against Aspergillus flavus.

Aspergillus flavus is a pathogenic fungus associated with food safety issues worldwide. This study investigated the antifungal activity of citrus peel extracts prepared using food-grade solvents (hot water or ethanol). Mandarin (Citrus reticulata) peel ethanol extracts inhibited the mycelial growth of A. flavus (39.60%) more effectively than those of orange (32.31%) and lemon (13.51%) after 7 days of incubation. The growth of A. flavus could be completely inhibited by mandarin extracts at 300-400 mg mL-1, depending on the extraction solvent. Solid-phase extraction (SPE) separated the polyphenol-rich fractions, which showed up to 40% higher antifungal activity than crude extracts. Twelve polyphenols (2 phenolic acids and 10 flavonoids) were identified by HPLC-DAD, narirutin and hesperidin were the most abundant. In conclusion, citrus peels are promising bioresources of antifungal agents with potential applications in food and other industries.

Starch Digestion Enhances Bioaccessibility of Anti-Inflammatory Polyphenols from Borlotti Beans (Phaseolus vulgaris).

The consumption of beans has been associated with chronic disease prevention which may be attributed to the polyphenols present in the seed coat and endosperm. However, their bioaccessibility is likely to be limited by interactions with bean matrix components, including starch, protein and fibre. The aim of this project was to evaluate the effect of domestic processing and enzymatic digestion on the bioaccessibility of polyphenols from Borlotti beans (Phaseolus vulgaris) and to test their anti-inflammatory properties in a macrophage cell model. In vitro digestion of cooked beans released twenty times more polyphenols (40.4 ± 2.5 mg gallic acid equivalents (GAE)/g) than domestic processing (2.22 ± 0.1 mg GAE/g), with starch digestion contributing to the highest release (30.9 ± 0.75 mg GAE/g). Fluorescence microscopy visualization of isolated bean starch suggests that polyphenols are embedded within the granule structure. LC-MS analysis showed that cooked Borlotti bean contain flavonoids, flavones and hydroxycinnamic acids, and cooked bean extracts exerted moderate anti-inflammatory effects by decreasing mRNA levels of IL1ß and iNOS by 25% and 40%, respectively. In conclusion, the bioaccessibility of bean polyphenols is strongly enhanced by starch digestion. These polyphenols may contribute to the health benefits associated with bean consumption.

Selective enzymatic lipophilization of anthocyanin glucosides from blackcurrant (Ribes nigrum L.) skin extract and characterization of esterified anthocyanins.

Anthocyanins (ANC) are hydrophilic and water-soluble polyphenolic plant pigments. The current barriers to successful application of ANC in the food, cosmetic and pharmaceutical industries are predominantly related to performance, stability, formulation properties, and color. Enzymatic acylation of ANC could increase their stability without compromising bioactivity and chromatic features. Lipophilization of ANC-rich blackcurrant skin extract with Candida antarctica lipase B and octanoic acid was selective to cyanidin and delphinidin glucosides, but not the corresponding rutinosides. The reaction was chemo- and regioselective for acylation at the primary alcohol of the glucose moieties, greatly facilitating separation of the different glycoside derivatives.

Enhancing the Potential Exploitation of Food Waste: Extraction, Purification, and Characterization of Renewable Specialty Chemicals from Blackcurrants ( Ribes nigrum L.).

Natural colorants were extracted from renewable botanical sources, specifically waste epicarp from the blackcurrant fruit pressing industry. A process was developed which used acidified water extraction followed by a solid-phase extraction (SPE) purification stage which allowed the production of an anthocyanin-rich extract in good yields (ca. 2% w/ w based on dry weight of raw material). The components in the extracts were extensively characterized by HPLC, mass spectrometry, IR, NMR, and UV-vis spectroscopy. HPLC confirmed presence of four anthocyanins: delphinidin-3- O-rutinoside (45%), cyanidin-3- O-rutinoside (31%), and the corresponding glucosides at 16% and 8%, respectively. On sequential liquid-liquid aqueous-organic partitioning of the post-SPE sample, monomeric anthocyanins (54.7%) and polymeric anthocyanins (18%) were found in the aqueous layer with 3- O-rutinosides of myricetin (3.1%) and quercetin (3.2%), while isopropylacetate achieved selective extraction of caffeic acid (3%), p-coumaric acid (5%), and myricetin (2.5%) and quercetin (3.2%) aglycons. 3- O-Glucosides of myricetin (3.1%) and quercetin (2%), along with nigrumin- p-coumarate (1%) and nigrumin ferulate (0.5%) were selectively extracted from the remaining aqueous fraction using ethyl acetate. This allowed for near total quantification of the blackcurrant extract composition.

Application of Anthocyanins from Blackcurrant ( Ribes nigrum L.) Fruit Waste as Renewable Hair Dyes.

There is much concern about the toxicological effects of synthetic hair dyes. As an alternative approach, renewable waste blackcurrant ( Ribes nigrum L.) fruit skins from the fruit pressing industry were extracted using acidified water with a solid-phase purification stage. Anthocyanin colorants were isolated in good yields (2-3% w/ w) and characterized by HPLC. Sorption of anthocyanins onto hair followed a Freundlich isotherm; anthocyanin-anthocyanin aggregation interactions enabled high buildup on the substrate. Sorption energy of cyanidin-3- O-glucoside (monosaccharide) > cyanidin-3- O-rutinoside (disaccharide), but sorption properties of different anthocyanin glucosides were very similar. Intense blue-colored dyeing on hair could be achieved with λmax-vis at 580 nm, typical of the anionic quinonoid base; it is suggested that hair provides an environment that enables the stabilization of the anionic quinonoid base on adsorption through association with cations in the hair and copigmentation effects. Dyeings were stable to multiple washes.

(16) O/(18) O Exchange of Aldehydes and Ketones caused by H2 (18) O in the Mechanistic Investigation of Organocatalyzed Michael, Mannich, and Aldol Reactions.

Organocatalyzed Michael, Mannich, and aldol reactions of aldehydes or ketones, as nucleophiles, have triggered several discussions regarding their reaction mechanism. H2 (18) O has been utilized to determine if the reaction proceeds through an enamine or enol mechanism by monitoring the ratio of (18) O incorporated into the final product. In this communication, we describe the risk of H2 (18) O as an evaluation tool for this mechanistic investigation. We have demonstrated that exchange of (16) O/(18) O occurs in the aldehyde or ketone starting material, caused by the presence of H2 (18) O and amine catalysts, before the Michael, Mannich, and aldol reactions proceed. Because the newly generated (18) O starting aldehydes or ketones and (16) O water affect the incorporation ratio of (18) O in the final product, the use of H2 (18) O would not be appropriate to distinguish the mechanism of these organocatalyzed reactions.

Catalytic enantioselective [4 + 2]-cycloaddition: a strategy to access aza-hexacycles.

The aza-Diels Alder reaction has become one of the most widely used synthetic tools for the preparation of N-containing 6-membered heterocycles. Numerous important developments have been reported to render this reaction catalytic and enantioselective. This tutorial review highlights strategies and recent advances to achieve high efficiency and selectivity through the use of organocatalysts and transition metal complexes, allowing also the extension of this transformation substrate scope.

Stereoselective hydrosilylation of enals and enones catalysed by palladium nanoparticles.

A highly versatile and efficient hydrosilylation method by palladium nanoparticle catalysis allows the direct and chemoselective synthesis of 1) enolsilanes of high isomeric purity, 2) saturated aldehydes or ketones, or 3) the corresponding saturated acetals from α,ß-unsaturated aldehydes or ketones. The choice of the product is determined by simply switching the solvent from THF to mixtures of THF/water or THF/alcohol.

Total synthesis and absolute configuration of the natural amino acid tetrahydrolathyrine.

The natural product tetrahydrolathyrine has been synthesized through an iminoiodane-mediated aziridination of a (2S)-allylglycinol derivative, which provided a 2:3 mixture of diastereoisomers. One of these diastereoisomers was converted to the natural product and the other to its C-4 epimer. The C-4 configuration was established from NOESY NMR analysis and X-ray structure of compounds derived from the non-natural diastereoisomer. Thus, tetrahydrolathyrine was shown to have the (2S,4R) absolute configuration.

A new supported reagent for the parallel synthesis of primary and secondary O-alkyl hydroxylamines through a base-catalyzed Mitsunobu reaction.

The growing field of applications of O-alkyl hydroxylamines in medicinal chemistry and chemical biology has motivated the search for a parallel synthesis. A solid-phase approach based on the alkylation by alcohols of a new supported N-hydroxyphthalimide reagent using a Mitsunobu reaction followed by methylaminolysis has been optimized. This study points out the importance of the linker and a specific base effect for the Mitsunobu reaction. A large variety of alcohols can be used to give with moderate to high yields diverse O-alkyl hydroxylamines in high purity.