Continuous-Flow Hofmann Rearrangement Using Trichloroisocyanuric Acid for the Preparation of 2-Benzoxazolinone

A continuous-flow preparation of 2-benzoxazolinone via the Hofmann rearrangement of salicylamide has been implemented employing trichloroisocyanuric acid as the stable and atom-economic chlorinating agent. The system was optimized to avoid solid accumulation and allow the preparation of hundreds of grams of the pure desired material over a working day. Furthermore, a trichloroisocyanuric acid (TCCA)-based chlorination of 2-benzoxazolone to the corresponding 5-chloro derivative was also carried out under batch conditions

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

Due to their intrinsic physical properties, which includes being able to perform as volatile liquids at room and biological temperatures, fragrance ingredients/intermediates make ideal candidates for continuous-flow manufacturing. This review highlights the potential crossover between a multibillion dollar industry and the flourishing sub-field of flow chemistry evolving within the discipline of organic synthesis. This is illustrated through selected examples of industrially important transformations specific to the fragrances and flavours industry and by highlighting the advantages of conducting these transformations by using a flow approach. This review is designed to be a compendium of techniques and apparatus already published in the chemical and engineering literature which would constitute a known solution or inspiration for commonly encountered procedures in the manufacture of fragrance and flavour chemicals

UWB processing applied to multifrequency radar sounders. The case of MARSIS and comparison with SHARAD

We readapt ultrawideband (UWB) processing to enhance the range resolution of the Mars Advanced Radar for Subsurface and Ionosphere Sounding (MARSIS) up to a factor of 6 (25 m). The technique provides for the estimation of radar signature over a wider spectrum via the application of wellknown super-resolution (SR) techniques to adjoining subbands. The measured spectra are first interpolated and then extrapolated outside the original bands. The revised algorithm includes the estimation and removal of ionospheric effects impacting the two signals. Because the processing requires the realignment of the echoes at different frequencies, we derived the maximum tolerable retracking error to obtain reliable super-resolved range profiles. This condition is fulfilled by low-roughness areas compared to MARSIS wavelength, which proves to be suitable for the application of our processing. Examples of super-resolved experimental products over different geological scenarios show the detection of shallow dielectric interfaces not visible from original MARSIS products. Our results are validated by comparison with the Shallow Radar (SHARAD) data acquired at the crossovers, demonstrating the potential of the method to provide enhanced imaging capabilities

Food Coloring Agents and Plant Food Supplements Derived from Vitis vinifera: A New Source of Human Exposure to Ochratoxin A

Grape pomaces are increasingly being used as starting material in the industrial production of plant food supplements (PFS), food coloring, and tartrates, but they are at risk of ochratoxin A (OTA) contamination, a mycotoxin with nephrotoxic and carcinogenic effects. We analyzed 24 commercial PFS and 13 food coloring samples derived from Vitis vinifera, mainly pomaces, using a HPLC−FLD method for OTA determination. OTA was found in 75% of PFS samples and 69% of food coloring samples at levels of <1.16−20.23 μg/kg and <1.16−32.00 μg/kg, respectively. The four commercial leavening agents containing tartrates were found to be negative for OTA. All eight samples collected in two distilleries that use grape pomaces and wine lees to produce tartrates and other byproducts contained OTA at levels of <1.16−240.93 μg/kg. The high incidence of OTA contamination in PFS and food coloring agents derived from V. vinifera suggests that maximum permitted level(s) should be established for this mycotoxin in these products

BASEL III: Long-term impact on economic performance and fluctuations

We assess the long-term economic impact of the new regulatory standards (the Basel III reform), answering the following questions. (1) What is the impact of the reform on long-term economic performance? (2) What is the impact of the reform on economic fluctuations? (3) What is the impact of the adoption of countercyclical capital buffers on economic fluctuations? The main results are the following. (1) Each percentage point increase in the capital ratio causes a median 0.09 percent decline in the level of steady state output, relative to the baseline. The impact of the new liquidity regulation is of a similar order of magnitude, at 0.08 percent. This paper does not estimate the benefits of the new regulation in terms of reduced frequency and severity of financial crisis, analysed in Basel Committee on Banking Supervision (BCBS, 2010b). (2) The reform should dampen output volatility; the magnitude of the effect is heterogeneous across models; the median effect is modest. (3) The adoption of countercyclical capital buffers could have a more sizeable dampening effect on output volatility. These conclusions are fully consistent with those of the reports by the Long-term Economic Impact group (BCBS, 2010b) and Macro Assessment Group (MAG, 2010b).Basel III, countercyclical capital buffers, financial (in)stability, procyclicality, macroprudential policy.

Phenols, volatiles and sensory properties of primitivo wines from the "Gioia Del Colle" PDO area

The aim of this study was to characterise the phenol, anthocyanin, volatile and sensory profiles of Primitivo wines. The wines were produced in three wineries located in the Gioia del Colle PDO (Protected Designation of Origin) area (Southern Italy - Apulia Region). The grapes came from three vineyards of different ages and were grown according to different training systems. The winemaking techniques applied also differed in some technological variables. The results obtained showed that all wines had a high alcohol content (15 to 16% v/v) and were rich in total phenols and proanthocyanidins. The anthocyanin profile was characterised by the prevalence of non-acylated forms, of which malvidin-3-O-monoglucoside accounted for 62 to 67% of the total anthocyanin, followed by the coumarate, acetate and caffeate forms. The volatile fraction was constituted mainly alcohols and esters, the latter having concentrations above the odour threshold. From a sensory point of view, all wines were judged positively, and presented high olfactory and gustatory persistence. The main odour attributes found were soft fruits, cherry and cloves

Discovery of a Potent Dual Inhibitor of Aromatase and Aldosterone Synthase.

Estrogen deficiency derived from inhibition of estrogen biosynthesis is a typical condition of postmenopausal women and breast cancer (BCs) patients undergoing antihormone therapy. The ensuing increase in aldosterone levels is considered to be the major cause for cardiovascular diseases (CVDs) affecting these patients. Since estrogen biosynthesis is regulated by aromatase (CYP19A1), and aldosterone biosynthesis is modulated by aldosterone synthase (CYP11B2), a dual inhibitor would allow the treatment of BC while reducing the cardiovascular risks typical of these patients. Moreover, this strategy would help overcome some of the disadvantages often observed in single-target or combination therapies. Following an in-depth analysis of a library of synthesized benzylimidazole derivatives, compound was found to be a potent and selective dual inhibitor of aromatase and aldosterone synthase, with IC values of 2.3 and 29 nM, respectively. Remarkably, the compound showed high selectivity with respect to 11β-hydroxylase (CYP11B1), as well as CYP3A4 and CYP1A2. When tested in cells, showed potent antiproliferative activity against BC cell lines, particularly against the ER+ MCF-7 cells (IC of 0.26 ± 0.03 μM at 72 h), and a remarkable pro-apoptotic effect. In addition, the compound significantly inhibited mTOR phosphorylation at its IC concentration, thereby negatively modulating the PI3K/Akt/mTOR axis, which represents an escape for the dependency from ER signaling in BC cells. The compound was further investigated for cytotoxicity on normal cells and potential cardiotoxicity against ERG and Nav1.5 ion channels, demonstrating a safe biological profile. Overall, these assays demonstrated that the compound is potent and safe, thus constituting an excellent candidate for further evaluation. [Abstract copyright: © 2023 The Authors. Published by American Chemical Society.

A simple one-pot oxidation protocol for the synthesis of dehydrohedione from Hedione

A new method for the oxidation of Hedione 1 to dehydrohedione 2, a high value intermediate in the flavour and fragrance industry, has developed based upon one pot α-chlorination-elimination sequence which can be readily scaled. The spontaneous elimination of the α-chloro in methanol was unprecedented and has allowed for the oxidation, typically performed in multiple steps/reactions, to be carried out as a one-pot protocol. A continuous flow process for performing the reaction utilising sulfuryl chloride has also demonstrated allowing for steady, safe evolution of SO2 gas during the reaction

Trimethoxylated halogenated chalcones as dual inhibitors of mao-b and bace-1 for the treatment of neurodegenerative disorders

Six halogenated trimethoxy chalcone derivatives (CH1–CH6) were synthesized and spec-trally characterized. The compounds were further evaluated for their inhibitory potential against monoamine oxidases (MAOs) and β-secretase (BACE-1). Six compounds inhibited MAO-B more effectively than MAO-A, and the 2′,3′,4′-methoxy moiety in CH4–CH6 was more effective for MAO-B inhibition than the 2′,4′,6′-methoxy moiety in CH1–CH3. Compound CH5 most potently inhibited MAO-B, with an IC50 value of 0.46 µM, followed by CH4 (IC50 = 0.84 µM). In 2′,3′,4′-methoxy derivatives (CH4-CH6), the order of inhibition was –Br in CH5 >-Cl in CH4 >-F in CH6 at the para-position in ring B of chalcone. CH4 and CH5 were selective for MAO-B, with selectivity index (SI) values of 15.1 and 31.3, respectively, over MAO-A. CH4 and CH5 moderately inhibited BACE-1 with IC50 values of 13.6 and 19.8 µM, respectively. When CH4 and CH5 were assessed for their cell viability studies on the normal African Green Monkey kidney cell line (VERO) using MTT assays, it was noted that both compounds were found to be safe, and only a slightly toxic effect was observed in concentrations above 200 µg/mL. CH4 and CH5 decreased reactive oxygen species (ROS) levels of VERO cells treated with H2 O2, indicating both compounds retained protective effects on the cells by antioxidant activities. All compounds showed high blood brain barrier permeabilities analyzed by a parallel artificial membrane permeability assay (PAMPA). Molecular docking and ADME prediction of the lead compounds provided more insights into the rationale behind the binding and the CNS drug likeness. From non-test mutagenicity and cardiotoxicity studies, CH4 and CH5 were non-mutagenic and non-/weak-cardiotoxic. These results suggest that CH4 and CH5 could be considered candidates for the cure of neurological dysfunctions