Fischer indole reaction in batch and flow employing a sulfonic acid resin: synthesis of pyrido[2,3-a]carbazoles

An Amberlite IR 120 H-promoted one-pot Fischer indolization from a cis-decahydroquinoline using a range of phenylhydrazines led to compounds with the pyrido[2,3-a]carbazole scaffold. The process may be conducted either in batch mode or in a continuous manner in a flow reactor. The stereochemical course of the Fischer indole reaction changed in going from using free phenylhydrazine to the corresponding hydrochloride in batch conditions, whereas, with the short reaction times in continuous flow, no changes due to isomerization processes were observed. Keywords: Fischer indole synthesis, one-pot synthesis, continuous-flow synthesis, sulfonic acid resin, immobilized reagents, pyrido[2,3-a]carbazole

Anti-Spike antibodies 3 months after SARS-CoV-2 mRNA vaccine booster dose in patients on hemodialysis: the prospective SENCOVAC study

Background: Patients on hemodialysis are at high-risk for complications derived from coronavirus disease 2019 (COVID-19). The present analysis evaluated the impact of a booster vaccine dose and breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on humoral immunity 3 months after the booster dose. Methods: This is a multicentric and prospective study assessing immunoglobulin G anti-Spike antibodies 6 and 9 months after initial SARS-CoV-2 vaccination in patients on hemodialysis that had also received a booster dose before the 6-month assessment (early booster) or between the 6- and 9-month assessments (late booster). The impact of breakthrough infections, type of vaccine, time from the booster and clinical variables were assessed. Results: A total of 711 patients [67% male, median age (range) 67 (20-89) years] were included. Of these, 545 (77%) received an early booster and the rest a late booster. At 6 months, 64 (9%) patients had negative anti-Spike antibody titers (3% of early booster and 29% of late booster patients, P =. 001). At 9 months, 91% of patients with 6-month negative response had seroconverted and there were no differences in residual prevalence of negative humoral response between early and late booster patients (0.9% vs 0.6%, P =. 693). During follow-up, 35 patients (5%) developed breakthrough SARS-CoV-2 infection. Antibody titers at 9 months were independently associated with mRNA-1273 booster (P =. 001), lower time from booster (P =. 043) and past breakthrough SARS-CoV-2 infection (P <. 001). Conclusions: In hemodialysis patients, higher titers of anti-Spike antibodies at 9 months were associated with mRNA-1273 booster, lower time from booster and past breakthrough SARS-CoV-2 infectionThe present project has been supported by Fresenius Medical Care, Diaverum, Vifor Pharma, Vircell, Fundación Renal Iñigo Álvarez de Toledo and ISCIII FEDER funds RICORS2040 (RD21/0005

Privileged heterocycles: bioactivity and synthesis of 1,9-diazaspiro[5.5]undecane-containing compounds

Contains fulltext : 181787.pdf (Publisher’s version ) (Open Access

New hybrid type strigolactone mimics derived from plant growth regulator auxin

Contains fulltext : 214611.pdf (postprint version ) (Open Access

Oxidation of Secondary Methyl Ethers to Ketones

We present a mild way of converting secondary methyl ethers into ketones using calcium hypochlorite in aqueous acetonitrile with acetic acid as activator. The reaction is compatible with various oxygen- and nitrogen-containing functional groups and afforded the corresponding ketones in up to 98% yield. The use of this methodology could expand the application of the methyl group as a useful protecting group

Assessing city-wide pharmaceutical emissions to wastewater via modelling and passive sampling

With increasing numbers of chemicals used in modern society, assessing human and environmental exposure to them is becoming increasingly difficult. Recent advances in wastewater-based epidemiology enable valuable insights into public exposure to data-poor compounds. However, measuring all >26,000 chemicals registered under REACH is not just technically unfeasible but would also be incredibly expensive. In this paper, we argue that estimating emissions of chemicals based on usage data could offer a more comprehensive, systematic and efficient approach than repeated monitoring. Emissions of 29 active pharmaceutical ingredients (APIs) to wastewater were estimated for a medium-sized city in the Netherlands. Usage data was collected both on national and local scale and included prescription data, usage in health-care institutions and over-the-counter sales. Different routes of administration were considered as well as the excretion and subsequent in-sewer back-transformation of conjugates into respective parent compounds. Results suggest model-based emission estimation on a city-level is feasible and in good agreement with wastewater measurements obtained via passive sampling. Results highlight the need to include excretion fractions in the conceptual framework of emission estimation but suggest that the choice of an appropriate excretion fraction has a substantial impact on the resulting model performance

Orthogonal, dual protein labelling by tandem cycloaddition of strained alkenes and alkynes to : Ortho -quinones and azides

Reaction of cyclopropanated trans-cyclooctene (cpTCO) with in situ generated ortho-quinone is an efficient tool for bioorthogonal protein conjugation. The (4+2)-cycloaddition of cpTCO with ortho-quinone is significantly faster than its cyclooctyne counterpart (BCN). Orthogonal, tandem cpTCO-quinone and BCN-azide cycloadditions afforded a homogeneous, dual labelled antibody-drug conjugate.</p

Fischer indole reaction in batch and flow employing a sulfonic acid resin: synthesis of pyrido[2,3-a]carbazoles

An Amberlite IR 120 H-promoted one-pot Fischer indolization from a cis-decahydroquinoline using a range of phenylhydrazines led to compounds with the pyrido[2,3-a]carbazole scaffold. The process may be conducted either in batch mode or in a continuous manner in a flow reactor. The stereochemical course of the Fischer indole reaction changed in going from using free phenylhydrazine to the corresponding hydrochloride in batch conditions, whereas, with the short reaction times in continuous flow, no changes due to isomerization processes were observed. Keywords: Fischer indole synthesis, one-pot synthesis, continuous-flow synthesis, sulfonic acid resin, immobilized reagents, pyrido[2,3-a]carbazole