Influence of anellation in N-heterocyclic carbenes: novel quinoxaline-anellated NHCs trapped as transition metal complexes

The synthesis, NMR-, and crystal structure data of novel electron-deficient quinoxaline anellated imidazol-2-ylidene precursors and complexes thereof are reported and compared with related less electron-withdrawing or non-anellated N-heterocyclic carbenes and complexes to illustrate anellation effects.     

Synthesis and Characterization of Metabolites and Potential Impurities of Balsalazide Disodium,an Anti-Inflammatory Drug

Balsalazide disodium (Colazide®) is an oral prodrug of mesalamine (5-aminosalicylic acid) and possesses anti-inflammatory properties. During the process development for balsalazide disodium, we observed eight impurities, namely des-β-alanine balsalazide, balsalazide β-alanine, balsalazide 3-isomer, decarboxy balsalazide, bis-azo salicylic acid, biphenyl-azo salicylic acid, bis-azo diacid, and bis-azo triacid. The present work describes the synthesis and characterization of these impurities.     

Novel Copolymers of Styrene. 6. Some Oxy Ring-Disubstituted Butyl 2-Cyano-3-Phenyl-2-Propenoates

Novel trisubstituted ethylenes, oxy ring-disubstituted butyl 2-cyano-3-phenyl-2-propenoates, RPhCH=C(CN)CO₂C₄H₉ (where R is 4-methoxy-2-methyl, 4-methoxy-3-methyl, 3-ethoxy-4-methoxy, 4-ethoxy-3-methoxy, 3,4-dibenzyloxy, 2-benzyloxy-3-methoxy, and 3-benzyloxy-4-methoxy) were prepared and copolymerized with styrene. The monomers were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-substituted benzaldehydes and butyl cyanoacetate, and characterized by CHN analysis, IR, ¹H and ¹³C-NMR. All the ethylenes were copolymerized with styrene (M₁) in solution with radical initiation (ABCN) at 70°C. The compositions of the copolymers were calculated from nitrogen analysis and the structures were analyzed by IR, ¹H and ¹³C-NMR.

Decomposition of the copolymers in nitrogen occurred in two steps, first in the 200-500°C range with residue (2-17 % wt.), which then decomposed in the 500-800°C range.     

Study a class of Hilfer fractional stochastic integrodifferential equations with Poisson jumps

Abstract

In this article, we derive the sufficient conditions for the existence of mild solutions of Hilfer fractional stochastic integrodifferential equations with nonlocal conditions and Poisson jumps in Hilbert spaces. Results will be obtained in the pth mean square sense by using the fractional calculus, semigroup theory and stochastic analysis techniques. The article generalizes many of the existing results in the literature in terms of (1) Riemann–Liouville and Caputo derivatives are the special cases. (2) In the sense of pth mean square norm. (3) Stochastic integrodifferential with nonlocal conditions and Poisson jumps. A numerical example is provided to validate the obtained theoretical results.     

Robust H_∞ control for uncertain Markovian jump systems with mixed delays

We scrutinize the problem of robust H∞control for a class of Markovian jump uncertain systems with interval timevarying and distributed delays. The Markovian jumping parameters are modeled as a continuous-time finite-state Markov chain. The main aim is to design a delay-dependent robust H∞control synthesis which ensures the mean-square asymptotic stability of the equilibrium point. By constructing a suitable Lyapunov–Krasovskii functional(LKF), sufficient conditions for delay-dependent robust H∞control criteria are obtained in terms of linear matrix inequalities(LMIs). The advantage of the proposed method is illustrated by numerical examples. The results are also compared with the existing results to show the less conservativeness.     

Silica-immobilized piperazine: A sustainable organocatalyst for aldol and Knoevenagel reactions

Silica-supported piperazine was found to be an efficient catalyst for aldol reactions of aromatic aldehydes and ketones with straightforward product isolation and catalyst reuse. Furthermore, the catalyst is active in Knoevenagel-type reactions to afford coumarin derivatives, using 2-methyltetrahydrofuran (2-MeTHF) as a novel bio-based solvent.     

Synthesis of Novel 4‐Substituted Coumarins,Docking Studies,and DHODH Inhibitory Activity

Coumarins are the important class of naturally occurring heterocyclic compounds. Activities like antioxidant, antibacterial, anti‐inflammatory, and anticancer have been reported for coumarin derivatives. Present work details the synthesis of substituted coumarin‐4‐pyrrolones as well as coumarin‐4‐acetyl amino acids and their DHODH inhibitory activity, which is a dual target for malaria and cancer. Coumarin‐4‐acetic acids ( 2a – c ) were coupled with different methyl esters of α‐amino acids ( 3 ) giving rise to corresponding coumarin‐4‐acetyl amino acid methyl esters ( 4a – o ), which on hydrolysis under basic condition underwent cyclization forming substituted dihydropyrrole‐2‐ones ( 5a – i ), dihydroindolizine‐3‐ones ( 5j – l ), and dihydropyrrolizin‐3‐one ( 5m – o ). Acidic hydrolysis of the compounds ( 4a – o ) yielded corresponding coumarin‐4‐acetyl amino acids ( 6a – f ). The docking study was performed with the protein 4IGH (obtained from PDB) using Surflex–Dock module. The newly synthesized compounds were tested for DHODH inhibitory activity using Brequinar as the standard. Compound 6b showed remarkable inhibition compared with the standard, and the other compounds with terminal COOH showed moderate inhibition.     

Inhibition of Cysteine Proteases by 6,6′-Dihydroxythiobinupharidine (DTBN) from Nuphar lutea

The specificity of inhibition by 6,6′-dihydroxythiobinupharidine (DTBN) on cysteine proteases was demonstrated in this work. There were differences in the extent of inhibition, reflecting active site structural-steric and biochemical differences. Cathepsin S (IC₅₀ = 3.2 μM) was most sensitive to inhibition by DTBN compared to Cathepsin B, L and papain (IC₅₀ = 1359.4, 13.2 and 70.4 μM respectively). DTBN is inactive for the inhibition of M^pro of SARS-CoV-2. Docking simulations suggested a mechanism of interaction that was further supported by the biochemical results. In the docking results, it was shown that the cysteine sulphur of Cathepsin S, L and B was in close proximity to the DTBN thiaspirane ring, potentially forming the necessary conditions for a nucleophilic attack to form a disulfide bond. Covalent docking and molecular dynamic simulations were performed to validate disulfide bond formation and to determine the stability of Cathepsins-DTBN complexes, respectively. The lack of reactivity of DTBN against SARS-CoV-2 M^pro was attributed to a mismatch of the binding conformation of DTBN to the catalytic binding site of M^pro. Thus, gradations in reactivity among the tested Cathepsins may be conducive for a mechanism-based search for derivatives of nupharidine against COVID-19. This could be an alternative strategy to the large-scale screening of electrophilic inhibitors.