Synthetic route optimization of Sumepirin antiepileptic drug candidate

In this work we describe the transformation of synthetic route of the antiepileptic drug candidate Sumepirin starting from discovery stage. Initial method included six step process requiring two steps of purification using colon chromatography and has poor overall yield of target compound. The process developed is convenient, scalable, technological and meet the most of conditions of green chemistry. The overall yield was increased up to 62.5% in four steps without colon chromatography purification which allows to obtain the target compound with purity of 99.5+% which is especially important for the active ingredient

SYNTHETIC ROUTE OPTIMIZATION OF SUMEPIRIN ANTIEPILEPTIC DRUG CANDIDATE

Epilepsy is one of the most common chronic diseases of the nervous system in the world, which affects both children and adults. 30% of patients with epilepsy are pharmacoresistant. Sumepirin 1 is a novel antiepileptic drug candidate developed in the Scientific and Educational Center of Pharmaceutics of the Kazan Federal University and having pronounced antiseizure effect and improved safety profile. This compound is pyridoxine-based molecule with residue of methanesulfonic acid in the 6th position of pyridoxine ring.This work was supported by subsidy allocated to Kazan Federal University for the state assignment in the sphere of scientificactivities (project number 0671-2020-0053

Two types of adsorbed water in natural montmorillonites at low temperatures by dielectric spectroscopy

Dielectric spectroscopy was applied to natural clay mineral - montmorillonite with the exchangeable K+ and Ni2+ cations where the effect of water adsorption in the samples on the dielectric response was examined in the temperature from -115°C to -75°C and frequency from 1 Hz to 1 MHz ranges. Two relaxation processes (1 and 2) were revealed. The process 1 was related to the adsorbed ordered water structures formed on the interior surface of interlayer channels while the relaxation process 2 was attributed to the disordered water structures built between two surface water monolayers

The Study of the Conformation and Dynamics of the New Quaternary Phosphonium Salts by NMR Spectroscopy

A number of quaternary phosphonium salts on the basis of pyridoxine derivatives were investigated by nuclear magnetic resonance (NMR) spectroscopy methods. Conformational exchange processes for each compound in solution were studied using dynamic NMR experiments. Energy barriers of the conformational transitions were determined. © 2014 Springer-Verlag Wien

Differences in behaviour of adsorbed water in kaolinites and montmorillonites in temperature range from -90°C to +140°C by dielectric spectroscopy

Two different types of natural layer aluminosilicates (clay minerals), montmorillonite with the exchangeable K+ and Ni2+ cations and kaolinite with the exchangeable K+ and Ba2+ cations, were investigated by dielectric spectroscopy. The different effects of water adsorption in montmorillonites and kaolinites on the dielectric response were observed in wide temperature (-90°C ÷ +140°C) and frequency (1 Hz ÷ 1 MHz) ranges. The influence of the nature of the hydration centers on adsorbed water dynamics and influence of ions nature on the activation energy values of the relaxation processes were discussed

Composition, stability, and lability of copper(II) dipeptide complexes

Complex formation of copper(II) with glycylglycine (HL) has been studied spectrophotometrically over a wide range of ligand concentration (0.005-1.0 mol dm-3) and pH (0.5-13) in aqueous potassium nitrate (1.0 mol dm-3 KNO3). The complexes [CuL]+, [Cu(HL)]2+, [Cu(LH-1)], [Cu(LH-1)(OH)]-, [Cu(LH-1)L]-, [Cu(LH-1)2]2-, and [Cu2(LH-1)2(OH)]- were found and their formation constants determined. The ligand in [Cu(HL)]2+ is co-ordinated through the carboxylate group, and the terminal amino group remains protonated. Such a co-ordination mode is more favourable for depeptides as compared to amino acids. Both of the ligands in [Cu(LH-1)2]2- are bound to the metal ion in a bidentate mode through the terminal amino nitrogen and the deprotonated peptide nitrogen. The species [Cu2(LH-1)2(OH·)]- has an intense absorption band in the near-u.v. region which indicates that the OH- group is bridging. The lability of complexes [Cu(LH-1)L]- with five aliphatic dipeptides has been investigated by n.m.r. relaxation of water protons. The ligand-exchange rates (Rex) in solutions of these complexes follow the kinetic equation Rex = (k1 + k2[L-])[Cu(LH-1)L-]. Increasing the size of the side chain of the dipeptides leads to a lower Rex, and a good correlation between log k2 and the steric constants Es0 of the side-chain substituents is observed. The high values for k1 obtained indicate a considerable trans effect of the deprotonated peptide group

Trimetaphosphate and imidazole—Possible reagents in prebiotic peptide synthesis

© 2016 Taylor & Francis Group, LLC.To develop the prebiotic peptide synthesis problem the oligopeptides formation kinetics in the glycine – sodium trimetaphosphate – imidazole system in water has been investigated in flow and batch conditions at different temperatures and pH values. The presence of sodium trimetaphosphate and alkaline conditions are necessary for oligoglycines formation. Imidazole increases yields of oligopeptides. The system investigated may be used as a good model for peptide synthesis in prebiotic conditions

EFFECT OF THE COMPOSITION OF Ni(II) AND Co(II) COMPLEXES ON ELECTRODEPOSITION OF THE METALS FROM CITRATE BATHS.

The addition of amino compounds to citrate nickel plating baths facilitates plating by raising the nickel current efficiency due to a postulated formation of Ni(II) heteroligand complexes. This paper reports the electrodeposition of nickel and cobalt with the composition and nature of complexes in citrate and citrate-glycinate baths. The systems Ni(II)-H//3Cit; Ni(II)-H//3Cit-HGly and CO(II)-H//3Cit; and CO(II)-H//3Cit-HGly were studied as to complex formation and electrodeposition over a range of pH at an approximately 1:1 ratio of the original complexant concentrations to those of the coordinated entities. The plating rate was found to be a function of the composition of the complex in solution

Structure, stability, and lability of copper(II) complexes with triglycine

Equilibrium constants of complex formation, rate constants of chemical exchange reactions, and characteristics of electronic absorption spectra for species detected in aqueous solution of copper(II) with triglycine were determined, and conclusions on the structure of the complexes were made. A possibility of H-bond formation between the ammonium group of the zwitter-ionic form of the ligand and the second peptide oxygen in the anionic form of an adjacent ligand was shown. Kinetics and mechanisms of ligand and proton exchanges in solutions of copper(II) bistripeptide complexes with the ligand containing a deprotonated peptide nitrogen atom were studied. A new mechanism was proposed for hydroxide-catalyzed substitution reactions in copper(II) complexes with tripeptides

Effect of the medium on the equilibrium between stereoisomeric six- and seven-membered cyclic chair-like acetals. Role of nonspecific and specific interactions

Principles for establishing the nature of solvation effects in stereoisomeric equilibria have been formulated. Using 1H NMR spectroscopy, the equilibrium constants have been determined in 12 solvents for the endo and exo isomers of 1,9,10,11,12,12-hexachloro-4,6-dioxatricyclo[7.2.1.02,8]dodec-10-ene which is characterized by a high barrier to stereoisomeric transformations. The results of correlation analysis have shown that solvation of the conformers with dissimilar orientations of the hexachloronorbornene fragment with respect to the chair-like acetal moiety is determined by the polarity and proton-acceptor properties of the medium. Comparison with the data on solvent effect on the equilibrium between 2-isopropyl-5-methoxy1,3-dioxane epimers suggests that the formation of H-complexes is controlled by electronic and conformational factors