Synthesis of (3S,5R)-cis- and (3S,5S)-trans-3,5-Dimethylvalerolactones and Their Conversion to Biotransformation Products of (S)-5-Ethyl-5-(2′-pentyl)barbituric Acid

(R,S)-5-Ethyl-5-(2′-pentyl)barbituric acid (I)^1,2 is metabolized in vivo to give all four possible optical isomers of 5-ethyl-5-(3′-hydroxy-1′-methylbutyl)barbituric acid (II). ^3,4 From metabolism studies of pure (1′S)- I and (1′3)-I, Palmer and co-workers^4,5 were able to determine the relative amounts of each of the four isomers formed. These studies showed that (1′S)-I gave mainly one enantiomer of (1′S)-II, whereas (1′R)-I gave approximately equal amounts of both (1′R)-II enantiomers.     

Kinetics and Mechanism of the Reaction between Barbituric Acid and Glycidol,Part III: Methylene Group Reaction with Glycidol at High Concentration

The reaction of barbituric acid and glycidol leads to formation of oligoetherols upon addition of glycidol both to the methylene group and imide groups of barbituric acid. The mechanism of reaction was established by kinetic studies on the reaction between 1,3‐dimethylbarbituric acid and glycidol used at high concentration. The obtained rate law and mechanism have been derived from kinetic studies and the results obtained before, where 1,3‐dimethylbarbituric acid and glycidol were used in comparable concentrations. The completed kinetic characteristics of the system is described. It has been found that glycidol reacted with methylene groups of 3‐dimethylbarbituric according to the equation: . The rate‐determining step was transformation of enolate into carbanion. Activation energy of the reaction was 61.3 kJ mol⁻¹ · K⁻¹. Proton transfer from methylene group of 1,3‐dimethylbarbituric into glycidol oxirane oxygen was observed by the ¹H‐NMR spectroscopy.     

Rosette formation by hydrogen bonding of 5,5-dialkylbarbituric acids with 2-amino-4,6-bis[5-(4′-aminophenyl)porphyrinatozinc]-1,3,5-triazines in solution

Porphyrin appended triazines (11a, 11b) and dialkylbarbituric acids (2a, 2b) were synthesised. The rosette formation by three-point intermolecular hydrogen-bonding interaction between substituted triazines and barbituric acid derivatives has been characterised in solution by UV–vis, IR, TGA–DTA and ESI-MS spectroscopy. The association constants of different combinations of host–guest moieties in equimolar quantities were determined by ¹H NMR titration studies in CDCl₃ at room temperature. The nature of substituents either on triazine or on barbituric acid were found to play a crucial role in rosette formation.

Formation of a supramolecular multiporphyrin rosette consisting of three units each of substituted barbituric acids and substituted triazines in solution.     

Synthesis of Novel Galactopyranosyl‐Derived Spiro Barbiturates

Abstract

Malonic acid undergoes condensation readily with ureas to yield barbituric acids 2, which on bromination give 5,5‐dibromobarbituric acids 3. Reaction of α‐D‐galactose with these 5,5‐dibromo barbituric acids afforded 2,3‐α‐D‐galactopyrano‐1,4‐dioxo‐7,9‐diaza‐spiro[4,5]deca‐6,8,10‐triones 4. The structures of the products have been assigned on the basis of ¹H NMR, ¹³C NMR, FAB‐MS, optical activity, and elemental analysis. The title compounds are found to have antibacterial and antifungal activities.     

Reaction of barbituric acid with organic azides and phosphonium ylides

Amination by organic azides has been carried out to provide aminobarbiturates by fusion of a triazole ring to the 5,6-positions of barbituric acid followed by cleavage and thermal elimination of nitrogen, whereas aza-Wittig reaction gave phosphoranylidene barbituric acid salts.      

Linear free energy relationship in thin layer chromatography of 5-arylidenebarbiturates

Summary Among 33 investigated 5-arylidenebarbiturates (I) and their N,N-dimethyl analogs (II) containing different substituents in the phenyl ring, 14 are new derivatives. Substituent effects of the phenyl ring on the ability of adsorption on silica gel were observed by TLC. The significant correlations between the R_M values and or ⁺ substient constants were found for both ortho-substituted derivatives of series I and N,N-di-methyl derivatives of series II. The mechanism of adsorption on the silica gel in relationships to our previous studies on barbituric acid derivatives is discussed.Part of this work has been presented at the Budapest Chromatography Conference, June 1–3, 1983.     

Synthesis of a new class of uridine phosphorylase inhibitors

A new series of potent uridine phosphorylase inhibitors have been prepared from barbituric acid. Among them, 1-[(2-hydroxyethoxy)methyl]-5-)(m--benzyloxy)benzylbarbituric acid ( 37 , BBBA) is the most promising having a K_i value of 1.1 ± 0.2 nM with uridine phosphorylase from human liver. The new inhibitors are easily synthesized and are better inhibitors of human uridine phosphorylase than their uracil counterparts.     

Applications of Laser-Raman spectroscopy to the analysis of polynucleotides containing uridine residues

Summary Qualitative characterization of uridine C(2)-endo-anti and C(3)-endo-anti forms has been carried out for the first time using Laser-Raman spectroscopy. Spectra are presented for some crystals containing the uridine residue whose conformations are known from their X-ray crystallographic analyses. Crystalline uridine and uridine 5-monophosphate as its lithium, sodium, potassium, barium and cadmium salts give Raman bands in the 600–700 cm^–1 range that seem to reflect sensitively and regularly the conformation of the uridine residue and, therefore, are proposed as convenient indicators of the above structures. A method for the determination of the uridine C(2)-endo-anti form in polyribonucleotides is also described. The usefulness of these characterizations in the conformational analysis of polyribonucleotides is shown.     

Selective,fast and semi-automatic enrichment of nucleosides by using a phenylboronic acid modified hybrid material composed of graphene oxide and melamine sponge

A hybrid material was prepared from graphene oxide and melamine sponge, and modified with phenylboronic acid to obtain a sorbent for the enrichment of the nucleosides cytidine, uridine, inosine, guanosine and adenosine. The loading capacity typically is around 27.8 mg g^?1 which is comparable to other sorbents, and highly selectivity for cis-diols is observed even if the concentration of potential interferents is 1500-fold higher. The sorbent was placed in an injector, and the process was operated semiautomatically by using a peristaltic pump. The sorbent is stable and can be re-used six times without decrease in efficiency. It was applied to the selective extraction of the cis-diols (cytidine, uridine, inosine, guanosine, adenosine) from HepG2 cells. It presents good linear between 3 to 5000 μg L^?1 and the limits of detection (in HPLC analysis with UV detection) are 1–4 μg L^?1. Good recoveries of 85–101% were obtained with spiked HepG2 cells samples, with relative standard deviation of ≤9.9%.

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Graphical abstract Schematic for the preparation of boronic acid modified graphene oxide/melamine sponge composite for in-syringe solid-phase extraction of nucleosides.

     

Azines and Azoles: CXX. Synthesis of Acyclic Analogs of N1-Ribosides of Barbituric Acid and Its 5-ylidene Derivatives

The reaction of 2,4,6-tris(trimethylsiloxy)pyrimidine with 2-oxabutane-1,4-diyl diacetate in methylene chloride in methylene chloride in the presence of SnCl₄ proceeds regioselectively to form 1-[(2-acetoxyethoxy)methyl]barbituric acid. The latter is readily deacetylated to a free acyclic analog of N-ribosides of barbituric acid. 1-[(2-Acetoxy- and 2-hydroxyethoxy)methyl]barbituric acids easily react with aromatic and heterocyclic aldehydes in water and organic solvents, forming 5-ylidenebarbituric acids. The structure of the products was proved by ¹H NMR and UV spectroscopy. Certain of the products exhibit a moderate antimicrobial and antiviral activity.     

15N-NMR-studies on the neutralization reaction of arylidene dimethyl barbituric acids organicLewis acids 38

The¹⁵N-NMR-spectra of benzylideneN,N-dimethyl barbituric acid andp-chloro-benzylideneN,N-dimethyl barbituric acid have been measured together with their addition products with piperidine and morpholine. TheLewis Acid reactivity is discussed in terms of¹⁵N-chemical shifts.Die¹⁵N-NMR-Spektren von Benzyliden-N,N-dimethylbarbitursäure undp-Chlorbenzyliden-N,N-dimethylbarbitursäure und deren Additionsprodukte mit Piperidin und Morpholin wurden gemessen und im Hinblick auf dieLewissäureaktivität dieser Substanzklasse interpretiert.

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¹⁵N-NMR-Untersuchungen über die Neutralisierungsreaktion von Arylidendimethylbarbitursäuren. OrganischeLewis-Säuren 38

     

Photometrische Bestimmung von Barbiturs?ure durch Kondensation mit Glutaconaldehyd

Zusammenfassung In Gegenwart eines großen Überschusses von Chloramin T, Kaliumcyanid und Pyridin bildet Barbitursäure durch Kondensation mit dem aus den oben genannten Reagentien gebildeten Glutaconaldehyd vorübergehend eine 11-Verbindung, deren Absorptionsmaximuni bei 502 nm liegt. Durch Messung der Extinktion mit der Linie Cd 509 läßt sich Barbitursäure — auch in Gegenwart der in 5-Stellung disubstituierten Barbitursäuren — quantitativ bestimmen. Die Fehler lagen zwischen –1,3 und +2,5%.

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Photometric determination of barbituric acid by condensation with glutaconaldehyde

An intermediate 11-compound with _max=502 nm is produced by a condensation reaction of barbituric acid and glutaconaldehyde the latter being produced from a large excess of chloramine T, potassium cyanide and pyridine. A method is described for the quantitative determination of barbituric acid in the presence of those barbituric acids disubstituted in 5-position by measuring the optical density of the above compound with the Cd-509 line. Errors were within the range of –1.3 to +2.5%.

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Für die Durchführung dieser Arbeit wurden dankenswerterweise Forsohungsmittel aus dem ERP-Sondervermögen bereitgestellt.Dem Verbande der Chemischen Industrie und der Deutschen Forschungsgemeinschaft, die diese Arbeit unterstützt haben, danken wir bestens.     

A new synthesis method for benzo[f]quinolin‐3‐carbonyl urea and thiourea derivatives in aqueous media catalyzed by TEBAC

A clean and simple synthesis procedure for benzo[f]quinolin‐3‐carbonyl urea and thiourea derivatives was developed based on the reaction between N‐arylidenenaphthalen‐2‐amine and barbituric acid or thiobarbituric acid in aqueous media catalyzed by triethylbenzylammonium chloride (TEBAC). It was interesting that the structures of products in solvent of DMSO‐d₆ solution were different from those of the crystal states, which keep the enol form. The products were characterized by ¹H NMR, and ¹³C NMR, and the crystal state was confirmed by X‐ray diffraction study of 3e . In addition, water was chosen as green solvent.     

Heavy metal ions in wines: meta-analysis of target hazard quotients reveal health risks

Background

Although the necessity of divalent magnesium and manganese for full activity of sugar nucleotidyltransferases and glycosyltransferases is well known, the role of these metal cations in binding the substrates (uridine 5'-triphosphate, glucose-1-phosphate, N-acetylglucosamine-1-phosphate, and uridine 5'-diphosphate glucose), products (uridine 5'-diphosphate glucose, uridine 5'-diphosphate N-acetylglucosamine, pyrophosphate, and uridine 5'-diphosphate), and/or enzyme is not clearly understood.

Results

Using isothermal titration calorimetry we have studied the binding relationship between the divalent metals, magnesium and manganese, and uridine 5'-phosphates to determine the role these metals play in carbohydrate biosynthesis. It was determined from the isothermal titration calorimetry (ITC) data that Mg⁺² and Mn⁺² are most tightly bound to PP _i , K_b = 41,000 ± 2000 M^-1 and 28,000 ± 50,000 M^-1 respectively, and UTP, K_b = 14,300 ± 700 M^-1 and 13,000 ± 2,000 M^-1 respectively.

Conclusion

Our results indicate that the formal charge state of the phosphate containing substrates determine the binding strength. Divalent metal cations magnesium and manganese showed similar trends in binding to the sugar substrates. Enthalpy of binding values were all determined to be endothermic except for the PP _i case. In addition, entropy of binding values were all found to be positive. From this data, we discuss the role of magnesium and manganese in both sugar nucleotidyltransferase and glycosyltransferase reactions, the differences in metal-bound substrates expected under normal physiological metal concentrations and those of hypomagnesaemia, and the implications for drug design.     

Structure of Potassium and Cesium Barbiturates

The structures of catena-[K(μ₆-Hba?O,O,O,O′,O′,O″)] (I) and catena-[Cs(μ₆-Hba–O,O,O′,O′,O″,O″)] (II), where Н₂ba is barbituric acid C₄H₄N₂O₃, were characterized by powder X-ray diffraction. Crystallographic data: a = 14.1603 (4) Å, b = 3.68977 (9) Å, c = 10.9508 (3) Å, β = 82.226 (1)°, V = 566.90 (3) ų, space group P2₁/n, Z = 4 for I; a = 14.652 (1) Å, b = 11.7275 (7) Å, c = 3.8098 (3) Å, β = 79.140 (6)°, V = 642.90 (8) ų, space group C2/m, Z = 4 for II. The structural topologies of alkali metal complexes with barbituric acid and some its derivatives were compared. The thermal stability of complexes I and II in an air atmosphere was studied.     

Synthesis of novel bis‐condensed heterocyclic ring assembly systems

The novel bis‐condensed heterocyclic systems with ring assemblies based on peripheral barbituric acid rings and central pyran, pyridine and thiine rings have been generated by the reaction of terephthalaldehyde and isophthalaldehyde with barbituric acid for comparison with the analogous systems generated with said dialdehydes and 1,3‐cyclohexanedione.     

Furanyl spiroketals: thermodynamic control of remote asymmetry

(E,E)-2-Alkyl-8-furanyl-1,7-dioxa-spiro[5.5]undecanes (1a-i) have been prepared in good yield and with very high diastereoselectivity from lactones (2a-e) and alkynes (3a,b) using lithium acetylide coupling, hydrogenation, desilylation and acid catalysed cyclisation/equilibration.     

Remarkable Change in Fluorescence Emission of Poly(diphenylacetylene) Film via in situ Desilylation Reaction: Correlation with Variations in Microporous Structure,Chain Conformation,and Lamellar Layer Distance

Fluorescence (FL) emission properties, microporous structures, energy‐minimized chain conformations, and lamellar layer structures of the silicon‐containing poly(diphenylacetylene) derivative of p‐PTMSDPA before and after desilylation were investigated. The nitrogen‐adsorption isotherms of p‐PTMSDPA film before and after desilylation were typical of type I, indicating microporous structures. The BET surface area and pore volume of the p‐PTMSDPA film were significantly reduced after the desilylation reaction, simultaneously, its FL emission intensity remarkably decreased. The theoretical calculation on both model compounds of p‐PTMSDPA and its desilylated polymer, PDPA, showed a remarkable difference in chain conformation: The side phenyl rings of p‐PTMSDPA are discontinuously arranged in a zig‐zag pattern, while the PDPA is continuously coiled in a helical manner. The lamellar layer distance (LLD) in the p‐PTMSDPA film significantly decreased after the desilylation reaction.

     

Reaction of 2-methylene-3-oxoquinuclidine with water,alcohols, and organic acids

2-Methylene-3-oxoquinuclidine (I) reacts with alcohols without acidic or alkaline catalysts to give 2-alkoxymethyl-3-oxoquinuclidines. In the case of protonation of I by weak acids (benzoic and barbituric acids) water molecules do not add to the double bond. Condensed heterocyclic systems that include the quinuclidine ring were obtained on the basis of 2-hydroxymethyl-3-hydroxy-²-dehydroquinuclidine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 948–951, July, 1981.