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.

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.

Revisiting unexploited antibiotics in search of new antibacterial drug candidates: the case of γ-actinorhodin.

Of the thousands of natural product antibiotics discovered to date, only a handful have been developed for the treatment of bacterial infection. The clinically unexploited majority likely include compounds with untapped potential as antibacterial drugs, and in view of the ever-growing unmet medical need for such agents, warrant systematic re-evaluation. Here we revisit the actinorhodins, a class that was first reported 70 years ago, but which remains poorly characterized. We show that γ-actinorhodin possesses many of the requisite properties of an antibacterial drug, displaying potent and selective bactericidal activity against key Gram-positive pathogens (including Staphylococcus aureus and enterococci), a mode of action distinct from that of other agents in clinical use, an extremely low potential for the development of resistance, and a degree of in vivo efficacy in an invertebrate model of infection. Our findings underscore the utility of revisiting unexploited antibiotics as a source of novel antibacterial drug candidates.

Mild extraction methods using aqueous glucose solution for the analysis of natural dyes in textile artefacts dyed with Dyer's madder (Rubia tinctorum L.).

Madder (Rubia tinctorum L.) has been widely used as a red dye throughout history. Acid-sensitive colorants present in madder, such as glycosides (lucidin primeveroside, ruberythric acid, galiosin) and sensitive aglycons (lucidin), are degraded in the textile back extraction process; in previous literature these sensitive molecules are either absent or present in only low concentrations due to the use of acid in typical textile back extraction processes. Anthraquinone aglycons alizarin and purpurin are usually identified in analysis following harsh back extraction methods, such those using solvent mixtures with concentrated hydrochloric acid at high temperatures. Use of softer extraction techniques potentially allows for dye components present in madder to be extracted without degradation, which can potentially provide more information about the original dye profile, which varies significantly between madder varieties, species and dyeing technique. Herein, a softer extraction method involving aqueous glucose solution was developed and compared to other back extraction techniques on wool dyed with root extract from different varieties of Rubia tinctorum. Efficiencies of the extraction methods were analysed by HPLC coupled with diode array detection. Acidic literature methods were evaluated and they generally caused hydrolysis and degradation of the dye components, with alizarin, lucidin, and purpurin being the main compounds extracted. In contrast, extraction in aqueous glucose solution provides a highly effective method for extraction of madder dyed wool and is shown to efficiently extract lucidin primeveroside and ruberythric acid without causing hydrolysis and also extract aglycons that are present due to hydrolysis during processing of the plant material. Glucose solution is a favourable extraction medium due to its ability to form extensive hydrogen bonding with glycosides present in madder, and displace them from the fibre. This new glucose method offers an efficient process that preserves these sensitive molecules and is a step-change in analysis of madder dyed textiles as it can provide further information about historical dye preparation and dyeing processes that current methods cannot. The method also efficiently extracts glycosides in artificially aged samples, making it applicable for museum textile artefacts.

Isolation and extraction of ruberythric acid from Rubia tinctorum L. and crystal structure elucidation.

Madder (Rubia tinctorum L.) has been exploited as a dye throughout history. The roots of the plant are very rich in the highly coloured glycosidic compounds ruberythric acid and lucidin primeveroside, alongside the corresponding aglycons which can be readily formed by deglycosylation, particularly during extraction. Supported by (1)H and (13)C NMR data, the conclusive X-ray crystal structure of the natural dye ruberythric acid is presented for the first time. The solid state structure revealed extensive intermolecular hydrogen bonding interactions between the sugar moieties in the unit cell, but only intramolecular hydrogen bonding through the hydroxyquinone groups. There is also some additional π-π stacking from the anthraquinone moiety.

Isolation and extraction of lucidin primeveroside from Rubia tinctorum L. and crystal structure elucidation.

Madder (Rubia tinctorum L.) has been used as a dye for over 2000 years with alizarin and purpurin the major natural dyes analysed from extractions undertaken. The use of ethanol as the solvent in the extraction process produced an extract that yielded four anthraquinone compounds lucidin primeveroside, ruberythric acid, alizarin and lucidin-ω-ethyl ether. Gravitational separation of the extract was used to record the first crystal structure of lucidin primeveroside, which is also the first ever known crystal structure of a glycoside containing anthraquinone moiety. The crystal structure along with (1)H and (13)C NMR helped elucidate and confirm the structure of this overlooked natural dye which has been shown to be a major compound in R. tinctorum L.

Ultra-fast microwave enhanced reversible addition-fragmentation chain transfer (RAFT) polymerization: monomers to polymers in minutes.

Microwave mediated RAFT polymerization leads to ultra-fast polymerizations, whilst keeping excellent control over molecular weights and molecular weight distributions; this is the first example of such a dramatic effect of microwaves on living radical polymerization kinetics, and it shows the potential for chemists to produce very well controlled polymers in a matter of minutes.

Stabilization of carbon dioxide-in-water emulsions by proteins.

At CO2 pressures between 40 and 100 bar, we have succeeded in creating very stable carbon dioxide-in-water emulsions using a relatively inexpensive and innocuous protein (principally beta-lactoglobulin) as the sole emulsifying agent.

Manipulation of the stereochemical outcome and product distribution in the Henry reaction using CO2 pressure.

The rate and stereocontrol of the Henry reaction in the presence of CO(2) can be controlled simply by manipulation of CO(2) pressure, and can be understood by consideration of the kinetic and thermodynamic aspects of the reaction.

An iterative approach to novel polyamines via nucleophilic ring-opening of aziridinium ions with beta-amino alcohols.

An iterative procedure for the synthesis of a novel class of synthetic polyamines has been developed, utilising the regioselective ring-opening of aziridinium ion intermediates; facile N-allyl deprotection of intermediate polyamines allows the rapid construction of high molecular weight, stereochemically defined compounds in a convergent manner.

Reactions in unusual media.

This review provides an introduction to three of the most well-developed solvent replacement strategies currently under investigation for synthetic chemistry: Ionic liquids, fluorous phase techniques, and supercritical carbon dioxide. They are all fascinating reaction media, and have considerable potential for use in pharmaceutical synthesis. However, this has to be balanced with problems and limitations of the new methods. This review aims to provide an overall account of recent advances in the use of unusual media for synthetic chemistry, with an emphasis on highlighting potential benefits, but also limitations, of each of the methods described.

Studies on the Lewis acid mediated cleavage of alpha-aminoacetals: synthesis of novel 1,2-aminoethers, and evidence for alpha-alkoxy aziridinium ion intermediates.

The nucleophilic cleavage of alpha-amino acetals induced by TMSOTf can be used to prepare a wide range of substituted 1,2-aminoethers. In particular, organometallic reagents, N-heterocycles, and enamines all react efficiently to give products in good yield. In appropriate cases, good levels of stereocontrol are possible, but this is very dependent on the nature of the nucleophile and the substrate, with diethylzinc proving particularly effective across a range of substrates. The degree of stereocontrol can be used to infer the nature of the reactive intermediates involved in the reaction. With diethylzinc, it is most likely that the reaction proceeds by coordination of the nucleophile to the amino group followed by transfer of an ethyl group to an alpha-oxocarbenium ion. With non-coordinating nucleophiles, the stereochemical outcome can be rationalised in terms of addition to the possible alpha-alkoxy aziridinium ion intermediates.

The Baylis-Hillman reaction in supercritical carbon dioxide: enhanced reaction rates, unprecedented ether formation, and a novel phase-dependent 3-component coupling.

The Baylis-Hillman reaction can be efficiently carried out in scCO2 with enhanced reaction rates relative to comparable solution phase reactions; at low pressures, a novel dimerisation is observed which has led to the development of a novel one-pot three component coupling reaction to form highly functionalized ethers.