Ribitol in Solution Is an Equilibrium of Asymmetric Conformations

Ribitol (C₅H₁₂O₅), an acyclic sugar alcohol, is present on mammalian α-dystroglycan as a component of O-mannose glycan. In this study, we examine the conformation and dynamics of ribitol by database analysis, experiments, and computational methods. Database analysis reveals that the anti-conformation (180°) is populated at the C3–C4 dihedral angle, while the gauche conformation (±60°) is seen at the C2–C3 dihedral angle. Such conformational asymmetry was born out in a solid-state ¹³C-NMR spectrum of crystalline ribitol, where C1 and C5 signals are unequal. On the other hand, solution ¹³C-NMR has identical chemical shifts for C1 and C5. NMR ³J coupling constants and OH exchange rates suggest that ribitol is an equilibrium of conformations, under the influence of hydrogen bonds and/or steric hinderance. Molecular dynamics (MD) simulations allowed us to discuss such a chemically symmetric molecule, pinpointing the presence of asymmetric conformations evidenced by the presence of correlations between C2–C3 and C3–C4 dihedral angles. These findings provide a basis for understanding the dynamic structure of ribitol and the function of ribitol-binding enzymes.     

Synthesis of N-aryl-2,2,2-trifluoroacetimidoyl piperazinylquinolone derivatives and their antibacterial evaluations

N-substituted trifluoroacetimidoyl chlorides were used for the synthesis of new piperazinylquinolone derivatives. These reactions provided N-aryl-2,2,2-trifluoroacetimidoyl piperazinylquinolone derivatives in good yields. Two selected compounds were evaluated for their antibacterial activities. These compounds displayed good antibacterial activities.     

High regioselectivity in electrochemical α-methoxylation of N-protected cyclic amines

N-Protecting groups of α-substituted cyclic amines strongly affected the regioselectivity in electrochemical methoxylation of these compounds. Namely, N-acyl derivatives were transformed into α′-methoxylated compounds, while N-cyano derivatives changed into α-methoxylated derivatives. Furthermore, Lewis acid catalyzed nucleophilic substitution of the α-methoxylated compounds protected with cyano group afforded α,α-disubstituted cyclic amines.     

Development in synthesis and electrochemical properties of thienyl derivatives of carbazole

A convenient and higher yielding synthetic route to N-alkyl-bis(thiophene)- and N-alkyl-bis(ethylenedioxythiophene) carbazole derivatives is reported and their aggregation, and electrochemical properties are characterized. The key step in the synthesis of this group of compounds has been the Stille-type coupling reaction between the N-alkyldibromocarbazole and tin derivatives of thiophene or ethylenedioxythiophene, as the best way for preparation of conjugated N-alkylcarbazole derivatives. For this group of compounds we also present an electrochemical polymerization effect.     

An efficient one-pot synthesis of spiro dihydrofuran fluorene and spiro 2-hydroxytetrahydrofuran fluorene derivatives via [3+2] oxidative cycloaddition mediated by CAN

Spiro dihydrofuran fluorene derivatives were prepared via [3+2] oxidative cycloaddition of 1,3-dicarbonyl compounds to 9-benzylidene-9H-fluorene and 2-(9H-fluorene-9-ylidene)-1-phenylethanone derivatives mediated by ceric ammonium nitrate. In the case of the reaction of 9-benzylidene-9H-fluorene with acyclic 1,3-dicarbonyl compounds, spiro 2-hydroxytetrahydrofuran fluorene derivatives were obtained.     

A new approach to the synthesis of lactams of muramic,isomuramic and normuramic acids via intramolecular O-alkylation: Stereochemical features of the intramolecular nucleophilic substitution

The title compounds were synthesized from the selectively protected N-acylated d-glucosamine derivatives, containing α-halo carboxylic acid moieties, via intramolecular 3-O-alkylation. It was found that if the starting compound contains asymmetric electrophilic center, isomuramic acid derivatives were mainly formed, regardless of the configuration of the electrophilic carbon atom. An explanation for the observed stereochemical results was proposed on the basis of the analysis of steric interactions in the molecules of the starting compounds, as well as using the concept of anchimeric assistance. It was shown that N-acetylation of the obtained lactam derivatives and subsequent methanolysis under mild conditions led to the selective cleavage of δ-lactam ring resulting in the formation of the corresponding ester derivatives of N-acetylmuramic acid or its analogues in high yields.     

Effect of substituents on the polarographic behaviour of α-arylhydrazononitriles: Further evidence for the mechanism of polarographic reduction of α-arylhydrazononitriles

The polarographic behaviour of the α-arylhydrazonomesoxalonitrile derivatives (IIb-i) and of 2-arylhydrazono-3-keto-3-phenylpropionitriles (IIIb-f) was investigated. With the exception of the nitro-substituted derivatives IIh, i and IIIf all the investigated compounds showed polarographic waves similar to that of their respective parent compounds IIa and IIIa. The m-nitro derivatives IIh and IIIf were firstly reduced in a 4 e wave to the corresponding hydroxylamino derivatives which were subsequently reduced in the manner common to other α-arylhydrazononitriles. On the other hand, the p-nitro derivative IIi was first reduced to the hydroxylamino derivative which then lost water to yield the corresponding quinoneimine. Reduction of the latter product in a 2 e wave gave the p-amino derivative IIe, which then underwent 4 e reduction to p-phenylenediamine and aminomalonitrile. The E_1/2 values corresponding to reduction of the arylhydrazonic moiety of compounds IIa-i and IIIa-f at different pH values were correlated to Hammett's different sigma sets. Analysis of the results provided evidence for the suggested mechanism for reduction of these compounds.     

Efficient Synthesis of Some Dichloroalditols: Direct Regioselective Chlorination of Some Unprotected Alditols by 1-Chlorocarbonyl-1-methylethyl Acetate

Abstract

Treatment of unprotected hexitols (D-glucitol, D-mannitol) and pentitols (D-arabinitol, xylitol and ribitol) with 1-chlorocarbonyl-1-methylethyl acetate (Me₂C(OAc)COCl), in 1,4-dioxane, leads to α,ω-dichloro derivatives in good yields. A route to some α,ω-dichloroacetoxy regioisomers has been elucidated.     

Integrating approach to discover novel bergenin derivatives and phenolics with antioxidant and anti-inflammatory activities from bio-active fraction of Syzygium brachythyrsum

Syzygium brachythyrsum is an important folk medicinal and edible plant in Yunnan ethnic minority community of China, however, little is known about the chemical and bio-active properties. The present study is aimed to identify the bioactive constituents with antioxidant and anti-inflammatory properties by an integrating approach. First, two new bergenin derivatives, brachythol A (1) and brachythol B (2), together with eleven known phenolic compounds (3–13) were isolated from bioactive fractions by phytochemical method. Among these isolated chemicals, five bergenin derivatives, along with 3 phenolics were found in Syzygium genus for the first time. Then, a further chemical investigation based on ultra-high-performance liquid chromatography-Q Exactive Orbitrap mass spectrometry resulted in a total of 107 compounds characterized in the bio-active fractions, including 50 bergenin derivatives, among which 14 bergenin derivatives and 14 phenolics were potential new natural chemicals. Most of the isolated compounds showed obvious antioxidant activities, while compounds 11, 12, and 13 had favorable performance. Eight compounds (2–5, 7, and 9–11) showed good inhibitory activity on nitric oxide (NO) production in macrophage RAW 264.7 cells. The structure–activity correlation analysis indicated that the antioxidation and anti-inflammatory activities enhanced when bergenin was esterified with gallic acid, caffeic acid or ferulic acid. This is the first report of bergenins in Syzygium genus and the richness in new bio-active bergenins and gallic acid derivatives indicated that Syzygium brachythyrsum is a promising functional and medicinal resource.     

Effects of Exogenous Methyl Jasmonate on the Biosynthesis of Shikonin Derivatives in Callus Tissues of Arnebia euchroma

The shikonin derivatives, accumulated in the roots of Arnebia euchroma (Boraginaceae), showed antibacterial, anti-inflammatory, and anti-tumor activities. To explore their possible biosynthesis regulation mechanism, this paper investigated the effects of exogenous methyl jasmonate (MJ) on the biosynthesis of shikonin derivatives in callus cultures of A. euchroma. The main results include: Under MJ treatment, the growth of A. euchroma callus cultures was not inhibited, but the expression level of both the genes involved in the biosynthesis of shikonin derivatives and their precursors and the genes responsible for intracellular localization of shikonin derivatives increased significantly in the Red Strain (shikonin derivatives high-producing strain). The quantitative analysis showed that six out of the seven naphthoquinone compounds under investigation increased their contents in the MJ-treated Red Strain, and in particular, the bioactive component acetylshikonin nearly doubled its content in the MJ-treated Red Strain. In addition, it was also observed that the metabolic profiling of naphthoquinone compounds changed significantly after MJ treatment, and the MJ-treated and MJ-untreated strains clearly formed distinct clusters in the score plot of PLS-DA. Our results provide some new insights into the regulation mechanism of the biosynthesis of shikonin derivatives and a possible way to increase the production of naphthoquinone compounds in A. euchroma callus cultures in the future.     

Determination of polyol profiles in human urine by capillary gas chromatography

A new rapid capillary gas chromatographic method is described for the profile analysis of urinary polyols as their trifluoroacetyl derivatives. Ten urinary polyols: erythritol, threitol, fucitol, ribitol, arabinitol, xylitol, mannitol, glucitol, galactitol and myo-inositol were completely determined for the first time. Iditol was newly found in normal urine. Urinary polyols were verified by gas chromatography/mass spectrometry.     

Atom-efficient synthesis of 2,6-diazacyclophane compounds through alcoholysis/reduction of 3-nitroarylmethylene-2,5-piperazinediones

Readily available cyclic dehydrodipeptides are convenient starting materials for atom-efficient synthesis of different compounds. A one-pot ring-opening/alcoholysis/hydrolysis process with 3-nitroarylmethylene-2,5-piperazinediones yielded N-3-nitroarylpyruvoylamino esters, which gave the corresponding amines by reduction of the nitro group. In the case of 2-nitroaryl compounds, an intramolecular reductive amination afforded N-indole-2-carbonylamino esters, while the intermolecular reductive amination of 3- and 4-nitroaryl derivatives allowed the synthesis of 2,6-diazacyclophanes. The amino compounds may be coupled with amino acids to get peptide-like derivatives.     

Understanding thermodynamic properties at the molecular level: multiple temperature charge density study of ribitol and xylitol

X-ray diffraction data of high quality measured to high resolution on crystals of the two pentitol epimers ribitol (centric) and xylitol (acentric) at 101, 141, and 181 K and data on the two compounds previously recorded at 122 K have formed the basis for multipole refinements with the VALRAY system. Our analysis showed that it is possible to obtain a reliable crystal electron density for an acentric compound (xylitol) from X-ray diffraction data and that the thermal motion can be deconvoluted from the static density in this temperature range. The Bader-type topological analysis of the static electron densities revealed virtually identical intramolecular interactions as well as very similar hydrogen bond interactions of ribitol and xylitol; the only minor differences are found in the weaker intermolecular interactions. The high-level periodic DFT calculations are in accordance with the thermodynamic measurements that show that the two pentitols have identical sublimation energies. A rigid body normal coordinate analysis was performed on the atomic displacement parameters obtained at the four different temperatures. The translational and librational mean square deviations derived through this analysis were used in a quantum statistical approach to derive frequencies of the corresponding harmonic oscillators. The analysis showed a consistent vibrational model for all temperatures. The frequencies were subsequently used to calculate crystal entropies assuming an Einstein-type behavior. These calculations show that the crystal entropy of ribitol is 8 J K(-1) mol(-1) higher than the crystal entropy of xylitol, confirming that it is a difference in the entropy of the two compounds that causes the difference in their free energy. Our results presented in this Article show the potential to use X-ray diffraction data to obtain physicochemical properties of crystals.     

Microwave promoted synthesis and antimicrobial activity of 3-thiazole substituted 2-styryl-4(3H)-quinazolinone derivatives

The present paper describes an optimized reaction condition for the microwave promoted synthesis of newer 3-thiazole substituted 2-styryl-4(3H)-quinazolinone derivatives, which in turn were prepared in good yield by the treatment of various 2-styryl benzoxazinone derivatives with various 2-aminothiazoles using co-solvent under microwave irradiation. All the compounds were characterized by various spectroscopic techniques and analytical methods. All newly synthesized compounds have been screened for their in vitro antibacterial and antifungal activities against Escherichia coli, Pseudomonas aeruginosa, Bacillus megaterium,Bacillus subtilis, and Aspergillus niger.     

Aromatic hydrocarbons as ligands. Recent advances in the synthesis,the reactivity and the applications of bis(η6-arene) complexes

Synthetic procedures for bis(η⁶-arene) metal derivatives and aspects of their reactivity are reviewed. Attention is focused on early transition metals (Groups 4–6) but, when necessary, reference will be made to arene derivatives of Groups 7–10, lanthanides and actinides.After a short historical presentation of bis(η⁶-arene) derivatives, aimed at illustrating the relevance of this class of compounds to the origin and the evolution of organometallic chemistry, the synthetic procedures to bis(η⁶-arenes) will be discussed in the light of the most recent results. As far as the reactivity of bis(η⁶-arene) compounds is concerned, particular attention is given to the electron transfer reactions occurring with or without arene displacement; data are reported for the use of low-valent bis(η⁶-arene) compounds as a useful entry into the inorganic and coordination chemistry of the corresponding metal in non aqueous systems.The use of bis(η⁶-arene) derivatives of transition metals in low oxidation states (0, +1) as precursors to catalytic systems for the oligomerisation and polymerization of unsaturated monomers and as starting compounds for the preparation of molecule-based magnets, ordered crystals and new materials and supports is described.     

Synthesis and properties of 2-azahetarylaminomethylidene 1,3-dicarbonyl compounds

Reactions of 2-ethoxymethylidene 1,3-dicarbonyl compounds with pyridine-2,6- and pyrimidine-4,5-diamines gave the corresponding 2-hetarylaminomethylidene derivatives. Depending on the initial reactant structure, the formation of mono-and/or bis-condensation products is possible. Hetarylaminomethylidene derivatives showed a moderate tuberculostatic effect. 2-Pyridinylaminomethylidene 3-oxo esters were used as ligands to obtain coordination compounds with d- and f-metal ions.     

Stereoselective synthesis of 1-C-alkyl iminogalactitol derivatives,potential chaperones for galactosidase-linked LSDs: a real challenge

1-C-Alkyl iminogalactitol derivatives are highly desirable target compounds as potential pharmacological chaperones for the treatment of galactosidase-linked lysosomal storage disorders (LSDs). The synthesis of such compounds from d-galactose by a C-1 chain extension process by way of an open-chain 6-amino d-gulo nonulose intermediate was complicated by unexpected deoxygenation reactions leading to 3-deoxy iminogalactitol derivatives and epimers; an alternative, stereocontrolled synthesis from an l-tagatose derivative by C-6 chain-extension was therefore developed, which involved addition of organometallic reagents onto t-butanesulfinylimine intermediates in the key step.     

Fluorescence lifetimes of several structurally rigid t-stilbene derivatives

Fluorescence lifetimes of t-stilbene and its structurally rigid derivatives, i.e. substituted tetrahydrochrysenes, are reported. Single component fluorescence decays are observed for all these compounds. These t-stilbene derivatives show the same spectral features as found in a spectrum of t-stilbene recorded at 77 K but with lower transition energies. All the t-stilbene derivatives have significantly longer fluorescence lifetimes in accordance with that of t-stilbene at lower temperatures.     

Discovery of Quinazoline-2,4(1H,3H)-Dione Derivatives as Potential Antibacterial Agent: Design,Synthesis, and Their Antibacterial Activity

In this paper, we report on the design and synthesis of a novel series of quinazoline-2,4(1H,3H)-dione derivatives as fluoroquinolone-like inhibitors of bacterial gyrase and DNA topoisomerase IV to identify and develop antimicrobial agents to prevent bacterial resistance problems. Their structures were confirmed using spectroscopic analyses (IR, NMR, and EI-MS). The novel quinazoline-2,4(1H,3H)-dione derivatives were evaluated for their antimicrobial activities against Gram-positive and Gram-negative bacterial strains using the Agar well diffusion method to study the antimicrobial activities and compared them with the standard drugs. Most compounds displayed moderate activity. Among the tested compounds, the most promising compounds 13 and 15 provided broad bioactive spectrum against Gram-positive and Gram-negative strains compared to the standard drugs.     

Combining α-amidoalkylation reactions of N-acyliminium ions with ring-closing metathesis: access to versatile novel isoindolones spirocyclic compounds

A novel approach to diversely spirocyclic isoindoles has been developed by using N-acyliminium/ring-closing metathesis strategy. Spirocyclization precursors, diolefinic, and enyne spiro-fused-isoindole derivatives have been obtained by a regioselective reduction of the spiro-imide compounds, followed by the allylation of the N-acyliminium intermediates (generated from the acetoxylactam compounds). Ruthenium catalyzed ring-closing metathesis of the above unsaturated derivatives provided novel spiroisoindoles.