Biodiesel and FAME synthesis assisted by microwaves: homogeneous batch and flow processes

Fatty acids methyl esters (FAME) have been prepared under microwave irradiation, using homogeneous catalysis, either in batch or in a flow system. The quality of the biodiesel obtained has been confirmed by GC analysis of the isolated product. While the initial experiments have been performed in a small scale laboratory batch reactor, the best experiment has been straightforward converted into a stop-flow process, by the use of a microwave flow system. Compared with conventional heating methods, the process using microwaves irradiation proved to be a faster method for alcoholysis of triglycerides with methanol, leading to high yields of FAME

Synthesis and in vivo evaluation of non-hepatotoxic acetaminophen analogs

A series of acetaminophen (APAP) analogs, 2-(1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)-N-(4-hydroxyphenyl)alkanecarboxamides, bearing a heterocyclic moiety linked to the p-acylaminophenol fragment, were prepared in a general project to develop APAP analogs with modulated pharmacokinetic profiles. Unexpectedly, the products described maintained the in vivo analgesic profile, while the characteristic hepatotoxicity of APAP was consistently reduced. One of the products, 5a, was studied in vivo in comparison with APAP. Compound 5a displayed an analgesic efficacy comparable to that of APAP. A relatively high acute oral dose of 5a (6 mmol/kg) produced no measurable toxicity, whereas the equimolar dose of APAP increased transaminase activity, depleted hepatic and renal glutathione, and resulted in mortality. In human hepatocytes (HEPG-2) and in human primary cultures of normal liver cells, APAP, but not 5a, was associated with apoptotic cell death, Fas-ligand up-regulation, and CAR (constitutive androstane receptor) activation, contributing to a favorable safety profile of 5a as an orally delivered analgesic.MDA972-03-C-010 (Defense Advanced Research Programs Agency-DARPA)Neurobiotechnology Program of Louisian

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

New uses of westphal condensation - synthesis of flavocorylene and related indolo[2,3-a]quinolizinium salts

Using the Westphal condensation, flavocorylene and related Indolo[2,3-a]-quinolizinium salts have been prepared in two steps, starting from commercially available β-carboline derivatives

New applications of westphal condensation. Synthesis of new [2.3.3]cyclazinones

Two different types of [2.3.3]cyclazinone isomers were obtained by methods based on the Westphal condensation. 2,6-Dialkylpyridinium salts were condensed with 1,2-acenaphtenequinone to produce [2.3.3]cyclazin-1-one derivatives. By a similar process, a quinolizinium-1-olate was prepared, which was cyclized with DMAD yielding a [2.3.3]cyclazin-6-one derivative.Comisión Asesora de Investigación Científica y Técnica-CAICY

New uses of the westphal condensation. Synthesis of pi-donor-pi-acceptor heterocycles

Novel pyrido[1,2-a] and pyridazino[2,3-a]-pyrrolo[2,1-c]pyrazin-7-ium derivatives have been prepared using Westphal condensation as an example of fused heterocycles with linked π-donor and π-acceptor moieties.Authors wish to acknowledge the assistance provided by LILLY S.A. in Nmr analysis, and to the Comisión Interministerial de Ciencia y Tecnología\ud (CICYT) for financial support ( Project PB87-0755