Anita R. Maguire

Modern Organic Synthesis with α-Diazocarbonyl Compounds

Alan Ford,† Hugues Miel, Aoife Ring,† Catherine N. Slattery,† Anita R. Maguire,*,†,‡ and M. Anthony McKervey* †Department of Chemistry and ‡School of Pharmacy, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork, Cork, Ireland Almac Discovery Ltd., David Keir Building, Stranmillis Road, Belfast BT9 5AG, United Kingdom Almac Sciences Ltd., Almac House, 20 Seagoe Industrial Estate, Craigavon BT63 5QD, United Kingdom

Fatty acid profile, tocopherol, squalene and phytosterol content of brazil, pecan, pine, pistachio and cashew nuts.

Nuts contain bioactive constituents that elicit cardio-protective effects including phytosterols, tocopherols and squalene. The objective of the present study was to determine the total oil content, peroxide value, fatty acid composition and levels of tocopherols, squalene and phytosterols in oil extracted from freshly ground brazil, pecan, pine, pistachio and cashew nuts. The total oil content of the nuts ranged from 40.4 to 60.8% (w/w) while the peroxide values ranged from 0.14 to 0.22 mEq O2/kg oil. The most abundant monounsaturated fatty acid was oleic acid (C18:1), while linoleic acid (C18:2) was the most prevalent polyunsaturated fatty acid. The levels of total tocopherols ranged from 60.8 to 291.0 mg/g. Squalene ranged from 39.5 mg/g oil in the pine nut to 1377.8 mg/g oil in the brazil nut. β-Sitosterol was the most prevalent phytosterol, ranging in concentration from 1325.4 to 4685.9 mg/g oil. In conclusion, the present data indicate that nuts are a good dietary source of unsaturated fatty acids, tocopherols, squalene and phytosterols.

Qualitative and quantitative comparison of the cytotoxic and apoptotic potential of phytosterol oxidation products with their corresponding cholesterol oxidation products

Phytosterols contain an unsaturated ring structure and therefore are susceptible to oxidation under certain conditions. Whilst the cytotoxicity of the analogous cholesterol oxidation products (COP) has been well documented, the biological effects of phytosterol oxidation products (POP) have not yet been fully ascertained. The objective of the present study was to examine the cytotoxicity of beta-sitosterol oxides and their corresponding COP in a human monocytic cell line (U937), a colonic adenocarcinoma cell line (CaCo-2) and a hepatoma liver cell line (HepG2). 7beta-Hydroxysitosterol, 7-ketositosterol, sitosterol-3beta,5alpha,6beta-triol and a sitosterol-5alpha,6alpha-epoxide-sitosterol-5beta,6beta-epoxide (6:1) mixture were found to be cytotoxic to all three cell lines employed; the mode of cell death was by apoptosis in the U937 cell line and necrosis in the CaCo-2 and HepG2 cells. 7beta-Hydroxysitosterol was the only beta-sitosterol oxide to cause depletion in glutathione, indicating that POP-induced apoptosis may not be dependent on the generation of an oxidative stress. A further objective of this study was to assess the ability of the antioxidants alpha-tocopherol, gamma-tocopherol and beta-carotene to modulate POP-induced cytotoxicity in U937 cells. Whilst alpha/gamma-tocopherol protected against 7beta-hydroxycholesterol-induced apoptosis, they did not confer protection against 7beta-hydroxysitosterol- or 7-ketositosterol-induced toxicity, indicating that perhaps COP provoke different apoptotic pathways than POP. beta-Carotene did not protect against COP- or POP-induced toxicity. In general, results indicate that POP have qualitatively similar toxic effects to COP. However, higher concentrations of POP are required to elicit comparable levels of toxicity.

Bioactivities of glycoalkaloids and their aglycones from Solanum species.

Potatoes, tomatoes, and aubergines are all species of the Solanum genus and contain a vast array of secondary metabolites including calystegine alkaloids, phenolic compounds, lectins, and glycoalkaloids. Glycoalkaloids have been the subject of many literature papers, occur widely in the human diet, and are known to induce toxicity. Therefore, from a food safety perspective further information is required regarding their analysis, toxicity, and bioavailability. This is especially important in crop cultivars derived from wild species to prevent glycoalkaloid-induced toxicity. A comprehensive review of the bioactivity of glycoalkaloids and their aglycones of the Solanum species, particularly focused on comparison of their bioactivities including their anticancer, anticholesterol, antimicrobial, anti-inflammatory, antinociceptive, and antipyretic effects, toxicity, and synergism of action of the principal Solanum glycoalkaloids, correlated to differences of their individual molecular structures is presented.

Taming Hazardous Chemistry in Flow: The Continuous Processing of Diazo and Diazonium Compounds

The synthetic utilities of the diazo and diazonium groups are matched only by their reputation for explosive decomposition. Continuous processing technology offers new opportunities to make and use these versatile intermediates at a range of scales with improved safety over traditional batch processes. In this minireview, the state of the art in the continuous flow processing of reactive diazo and diazonium species is discussed.

Comparison of the cytotoxic effects of β-sitosterol oxides and a cholesterol oxide, 7β-hydroxycholesterol, in cultured mammalian cells

Phytosterols are plant sterols found in foods such as oils, nuts and vegetables. Phytosterols, in the same way as cholesterol, contain a double bond and are susceptible to oxidation. The objective of the present study was to assess the potential toxic effects of β-sitosterol oxides on U937 cells. The effects of increasing concentrations (0-120 μM) of β-sitosterol oxides on cellular cytotoxicity, apoptosis, anti-oxidant status and genotoxicity was assessed over 12, 24 and 48h exposure periods. Following 12h, the viability of cells treated with 120 μM-β-sitosterol oxides was reduced to 51·7% relative to control. At 24 and 48 h, both 60 and 120 μM-β-sitosterol oxides caused a significant decrease in cell viability. For comparison, a decrease in viability of cells treated with a cholesterol oxide, 7β-hydroxycholesterol (7β-OH, 30 μM), was evident at 24 h. An increase in apoptotic cells, assessed using Hoechst 33342, indicates that the mode of cell death in U937 cells following exposure to 7β-OH (30 μM) and β-sitosterol oxides (60 and 120 μM) was by apoptosis. The increase in apoptotic cells after 12h following treatment with 120 μM-β-sitosterol oxides was accompanied by a decrease in cellular glutathione. Similarly, 7β-OH (30 μM) treatment resulted in decreased glutathione at 12 h. Catalase activity was not affected by any of the treatments. β-Sitosterol oxides had no genotoxic effects on U937 and V79 cells as assessed by the comet and sister chromatid exchange assays respectively. In general, the results indicate that thermally oxidised derivatives of β-sitosterol demonstrate similar biological effects as 7β-OH in U937 cells, but at higher concentrations.

Asymmetric synthesis in carbon–carbon bond forming reactions of α-diazoketones catalysed by homochiral rhodium(II) carboxylates

Partial asymmetric synthesis has been observed in intramolecular C–H insertion, aromatic cycloaddition, and cyclopropanation reactions of α-diazoketones catalysed by homochiral rhodium(II) mandelate and rhodium(II) carboxylates derived from L-proline.

Highly Enantioselective Intramolecular Copper Catalyzed C−H Insertion Reactions of α-Diazosulfones

Excellent enantiocontrol (up to 98% ee) is achieved in copper catalyzed C-H insertions of alpha-diazosulfones to form thiopyrans, with up to 60% ee in C-H insertions leading to sulfolanes.

Phytosterol Oxidation Products: Their Formation, Occurrence, and Biological Effects

Phytosterols or plant sterols are integral natural components of plant cell membranes that are abundant in vegetable oils, nuts, seeds, and grains; as well as added components in various functional foods. Due to their chemical structure, phytosterols are susceptible to oxidation under certain conditions giving rise to a family of compounds known as phytosterol oxidation products (POPs). The following review gives an in-depth account on the formation and occurrence of POPs in foodstuffs. The metabolism and biological effects of these oxides is also discussed in detail.

ReactNMR and ReactIR as reaction monitoring and mechanistic elucidation tools: the NCS mediated cascade reaction of α-thioamides to α-thio-β-chloroacrylamides.

On-flow ReactIR and (1)H NMR reaction monitoring, coupled with in situ intermediate characterization, was used to aid in the mechanistic elucidation of the N-chlorosuccinimide mediated transformation of an α-thioamide. Multiple intermediates in this reaction cascade are identified and characterized, and in particular, spectroscopic evidence for the intermediacy of the chlorosulfonium ion in the chlorination of α-thioamides is provided. Further to this, solvent effects on the outcome of the transformation are discussed. This work also demonstrates the utility of using a combination of ReactIR and flow NMR reaction monitoring (ReactNMR) for characterizing complex multicomponent reaction mixtures.