Stuart G. Collins

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.

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.

Anti-inflammatory properties of potato glycoalkaloids in stimulated Jurkat and Raw 264.7 mouse macrophages.

AIMS The potato glycoalkaloids, α-chaconine, α-solanine and solanidine, along with potato peel extracts were investigated for potential anti-inflammatory effects in vitro. Their potential to reduce two biomarkers of inflammation, cytokine and nitric oxide (NO) productions, were assessed in the stimulated Jurkat and macrophage models, respectively. MAIN METHODS Cytokine and nitric oxide productions were stimulated in Jurkat and Raw 264.7 macrophages with Concanavalin A (Con A; 25 μg/ml) and lipopolysaccaride (LPS; 1 μg/ml), respectively. Selective concentrations of glycoalkaloids and potato peel extracts were added simultaneously with Con A or LPS for 24h to investigate their potential to reduce inflammatory activity. KEY FINDINGS α-Chaconine and solanidine significantly reduced interleukin-2 (IL-2) and interleukin-8 (IL-8) productions in Con A-induced Jurkat cells. The potato peel extracts did not influence cytokine production. In LPS-stimulated Raw macrophages, α-solanine, solanidine and two potato peel extracts significantly reduced induced NO production. SIGNIFICANCE Our findings suggest that sub-cytotoxic concentrations of potato glycoalkaloids and potato peel extracts possess anti-inflammatory effects in vitro and with further investigation may be useful in the prevention of anti-inflammatory diseases.

Cell-based impedance spectroscopy for probing inhibitory effects of steroids and ergostane/lanosta-related compounds

Electric cell–substrate impedance sensing (ECIS) was used for probing inhibitory effects on Spodoptera frugiperda Sf9 insect cells exposed to five synthesized steroid compounds. The results were compared to the levels obtained using three ergostane-related steroids and five lanosta-related triterpenes purified from the fruiting bodies of Antrodia camphorata. The half-inhibition concentration (ECIS50), the level of 50% inhibition of the resistance response, was determined from the response function to establish inhibitory effects of the different compounds. Significant effects on inhibition as probed by impedance spectroscopy were noticed because of slight changes in chemical structure. Only two of the synthesized compounds, 24(R,S)-5α-lanost-8-ene-3,24,25-triol and 5α-lanost-8-ene-3,7,11-trione, showed inhibitory effects which were much less significant compared to the A. camphorata steroids. The ECIS50 values were 150–250 µM, similar to the value for the least inhibitory lanosta-related triterpene. This noninvasive measurement in combination with Sf9 insect cells has been proven as a simple and reliable tool for screening inhibition/cytotoxicity and designing steroid-related compounds.

Synthesis of Cyclic α-Diazo-β-keto Sulfoxides in Batch and Continuous Flow

Diazo transfer to β-keto sulfoxides to form stable isolable α-diazo-β-keto sulfoxides has been achieved for the first time. Both monocyclic and benzofused ketone derived β-keto sulfoxides were successfully explored as substrates for diazo transfer. Use of continuous flow leads to isolation of the desired compounds in enhanced yields relative to standard batch conditions, with short reaction times, increased safety profile, and potential to scale up.

Studies towards a greener diazo transfer methodology

A very mild, efficient and green method has been developed for diazo transfer to a range of β-ketoesters using polystyrene-supported benzenesulfonyl azide, water as solvent and a catalytic amount of base. This methodology eliminates the need for a standard work up and purification which is usually required to remove the sulfonamide by-product from the reaction.

Delivering enhanced efficiency in the synthesis of α-diazosulfoxides by exploiting the process control enabled in flow

Continuous-flow generation of α-diazosulfoxides results in a two- to three-fold increase in yields and decreased reaction times compared to standard batch synthesis methods. These high yielding reactions are enabled by flowing through a bed of polystyrene-supported base (PS-DBU or PS-NMe2) with highly controlled residence times. This engineered solution allows the α-diazosulfoxides to be rapidly synthesized while limiting exposure of the products to basic reaction conditions, which have been found to cause rapid decomposition. In addition to improved yields, this work has the added advantage of ease of processing, increased safety profile, and scale-up potential.

Synthesis of novel 24-amino-25,26,27-trinorlanost-8-enes: Cytotoxic and apoptotic potential in U937 cells

In the present study, the synthesis of a range of novel 24-amino-25,26,27-trinorlanost-8-ene derivatives including 24-piperadino-trinorlanost-8-enes, 24-piperazino-trinorlanost-8-enes, 24-morpholino-trinorlanost-8-enes, and 24-diethylamino-trinorlanost-8-enes is reported and their cytotoxic and apoptotic potential evaluated in U937 cell lines. Excellent IC₅₀ results for piperidine and 1-(2-hydroxyethyl)piperazine derivatives have been observed (IC₅₀ values of 1.9 μM and 2.7 μM in U937 cells, respectively).

Development of a continuous process for α-thio-β-chloroacrylamide synthesis with enhanced control of a cascade transformation

A continuous process strategy has been developed for the preparation of α-thio-β-chloroacrylamides, a class of highly versatile synthetic intermediates. Flow platforms to generate the α-chloroamide and α-thioamide precursors were successfully adopted, progressing from the previously employed batch chemistry, and in both instances afford a readily scalable methodology. The implementation of the key α-thio-β-chloroacrylamide casade as a continuous flow reaction on a multi-gram scale is described, while the tuneable nature of the cascade, facilitated by continuous processing, is highlighted by selective generation of established intermediates and byproducts.