Modifications to the Vilsmeier‐Haack formylation of 1,4‐dimethylcarbazole and its application to the synthesis of ellipticines

An improved method for the preparation of 3‐formyl‐1,4‐dimethylcarbazole, a key intermediate in the synthesis of ellipticine, is presented. Conditions of the Vilsmeier‐Haack reaction have been modified to facilitate the production of 3‐formyl‐1,4‐dimethylcarbazole as a major product leading to an overall improvement in yield of ellipticine from 3% to 14%. This approach was also applied to the synthesis of 6‐methylellipticine and 9‐methoxyellipticine. J. Heterocyclic Chem., (2011).     

Deprotonative metalation of aromatic compounds by using an amino-based lithium cuprate

Deprotonative cupration of aromatic compounds by using amino‐based lithium cuprates was optimized with 2,4‐dimethoxypyrimidine and 2‐methoxypyridine as the substrates and benzoyl chloride as the electrophile. [(tmp)₂CuLi] (+2 LiCl) (tmp=2,2,6,6‐tetramethylpiperidino) was identified as the best reagent and its use was extended to anisole, 1,4‐dimethoxybenzene, other substituted pyridines, furan, thiophene and derivatives, and N‐Boc‐indole (Boc=tert‐butyloxycarbonyl). Of the electrophiles employed to attempt the interception of the generated aryl cuprates, aroyl chlorides, iodomethane, and diphenyl disulfide efficiently reacted. In addition, different oxidative agents were identified to afford symmetrical biaryls. Finally, palladium‐catalyzed coupling with aryl halides was optimized and allowed the synthesis of different aryl derivatives in medium to good yields.     

Photo-SRM: laser-induced dissociation improves detection selectivity of Selected Reaction Monitoring mode

Selected Reaction Monitoring (SRM) carried out on triple‐quadrupole mass spectrometers coupled to liquid chromatography has been a reference method to develop quantitative analysis of small molecules in biological or environmental matrices for years and is currently emerging as a promising tool in clinical proteomic. However, sensitive assays in complex matrices are often hampered by the presence of co‐eluted compounds that share redundant transitions with the target species. On‐the‐fly better selection of the precursor ion by high‐field asymmetric waveform ion mobility spectrometry (FAIMS) or increased quadrupole resolution is one way to escape from interferences. In the present work we document the potential interest of substituting classical gas‐collision activation mode by laser‐induced dissociation in the visible wavelength range to improve the specificity of the fragmentation step. Optimization of the laser beam pathway across the different quadrupoles to ensure high photo‐dissociation yield in Q2 without detectable fragmentation in Q1 was assessed with sucrose tagged with a push‐pull chromophore. Next, the proof of concept that photo‐SRM ensures more specific detection than does conventional collision‐induced dissociation (CID)‐based SRM was carried out with oxytocin peptide. Oxytocin was derivatized by the thiol‐reactive QSY® 7 C₅‐maleimide quencher on cysteine residues to shift its absorption property into the visible range. Photo‐SRM chromatograms of tagged oxytocin spiked in whole human plasma digest showed better detection specificity and sensitivity than CID, that resulted in extended calibration curve linearity. We anticipate that photo‐SRM might significantly improve the limit of quantification of classical SRM‐based assays targeting cysteine‐containing peptides. Copyright © 2011 John Wiley & Sons, Ltd.     

Targeted and Untargeted Mass Spectrometry-Based Metabolomics for Chemical Profiling of Three Coffee Species

While coffee beans have been studied for many years, researchers are showing a growing interest in coffee leaves and by-products, but little information is currently available on coffee species other than Coffea arabica and Coffea canephora. The aim of this work was to perform a targeted and untargeted metabolomics study on Coffea arabica, Coffea canephora and Coffea anthonyi. The application of the recent high-resolution mass spectrometry-based metabolomics tools allowed us to gain a clear overview of the main differences among the coffee species. The results showed that the leaves and fruits of Coffea anthonyi had a different metabolite profile when compared to the two other species. In Coffea anthonyi, caffeine levels were found in lower concentrations while caffeoylquinic acid and mangiferin-related compounds were found in higher concentrations. A large number of specialized metabolites can be found in Coffea anthonyi tissues, making this species a valid candidate for innovative healthcare products made with coffee extracts.     

Learning PDE to Model Self-Organization of Matter

A self-organization hydrodynamic process has recently been proposed to partially explain the formation of femtosecond laser-induced nanopatterns on Nickel, which have important applications in optics, microbiology, medicine, etc. Exploring laser pattern space is difficult, however, which simultaneously (i) motivates using machine learning (ML) to search for novel patterns and (ii) hinders it, because of the few data available from costly and time-consuming experiments. In this paper, we use ML to predict novel patterns by integrating partial physical knowledge in the form of the Swift-Hohenberg (SH) partial differential equation (PDE). To do so, we propose a framework to learn with few data, in the absence of initial conditions, by benefiting from background knowledge in the form of a PDE solver. We show that in the case of a self-organization process, a feature mapping exists in which initial conditions can safely be ignored and patterns can be described in terms of PDE parameters alone, which drastically simplifies the problem. In order to apply this framework, we develop a second-order pseudospectral solver of the SH equation which offers a good compromise between accuracy and speed. Our method allows us to predict new nanopatterns in good agreement with experimental data. Moreover, we show that pattern features are related, which imposes constraints on novel pattern design, and suggest an efficient procedure of acquiring experimental data iteratively to improve the generalization of the learned model. It also allows us to identify the limitations of the SH equation as a partial model and suggests an improvement to the physical model itself.     

Structure and Computational Studies of New Sulfonamide Compound: {(4-nitrophenyl)sulfonyl}tryptophan

Synthesis of sulfonamide through an indirect method that avoids contamination of the product with no need for purification has been carried out using the indirect process. Here, we report the synthesis of a novel sulfonamide compound, ({4-nitrophenyl}sulfonyl)tryptophan (DNSPA) from 4-nitrobenzenesulphonylchloride and L-tryptophan precursors. The slow evaporation method was used to form single crystals of the named compound from methanolic solution. The compound was characterized by X-ray crystallographic analysis and spectroscopic methods (NMR, IR, mass spectrometry, and UV-vis). The sulfonamide N-H NMR signal at 8.07–8.09 ppm and S-N stretching vibration at 931 cm⁻¹ indicate the formation of the target compound. The compound crystallized in the monoclinic crystal system and P2₁ space group with four molecules of the compound in the asymmetric unit. Molecular aggregation in the crystal structure revealed a 12-molecule aggregate synthon sustained by O-H⋯O hydrogen bonds and stabilised by N-H⋯O intermolecular contacts. Experimental studies were complemented by DFT calculations at the B3LYP/6-311++G(d,p) level of theory. The computed structural and spectroscopic data are in good agreement with those obtained experimentally. The energies of interactions between the units making up the molecule were calculated. Molecular docking studies showed that DNSPA has a binding energy of −6.37 kcal/mol for E. coli DNA gyrase (5MMN) and −6.35 kcal/mol for COVID-19 main protease (6LU7).     

Lateral Deprotometallation-Trapping Reactions on Methylated Pyridines,Quinolines and Quinoxalines Using Lithium Diethylamide

The functionalization of methylated azines and diazines has aroused the interest of chemists given the structural diversity that it affords. Hindered lithium dialkylamides have been used to deprotometallate these substrates chemoselectively. In contrast, it can be observed that, despite some promising work, lithium diethylamide has been used very little for this purpose. Our objective here is on the one hand to make an inventory of what reagents have been used to deprotometallate methylpyridines, -quinolines and -quinoxalines, and on the other hand to describe the results obtained by seeking to functionalize a series of substrates with lithium diethylamide (picolines, 2,4-lutidine, methylquinolines and 2-methylquinoxaline). Our efforts to take advantage of the use of an in-situ trap (a zinc chloride chelate) in these reactions are also described.     

Nanostructured TiO2 as anode material for magnesium-ion batteries

Journal of Solid State Electrochemistry - The nanotubular structure of titanium dioxide (TiO2) is most suitable for creating high-performance energy storage and conversion devices. This paper...