Anion-directed assembly of metal-organic coordination complexes from 1,3-imidazolidine-2-thione ligand and silver salts

Five novel silver (Ι) complexes with 1,3-imidazolidine-2-thione ligand formulated as [Ag₂(η¹-SC₃H₆N₂)₆]SO₄ (1), [Ag₂(μ₂-SC₃H₆N₂)₂(η¹-SC₃H₆N₂)₄](NO₃)₂ (2), [Ag(μ₂-SC₃H₆N₂)Br]_n (3), [Ag₂(μ₂-SC₃H₆N₂)₃(CH₃COO)₂]_n (4), [Ag(μ₂-SC₃H₆N₂)Cl]_n (5) have been synthesized under similar conditions except for different anions and solvents. They are structurally characterized by elemental analysis, IR, TG and single crystal X-ray diffraction. Complex 1 is a binuclear complex, with SO₄²⁻ anions as the counteranions. Complex 2 is a molecular binuclear silver cluster, with NO₃⁻ anions as the counteranions. Complex 3 shows a novel 2D lamella structure constructed by the S atom of 1,3-imidazolidine-2-thione ligand and Br⁻ anions, and exhibits 12-membered metallacyclic rings in its structure. Complex 4 is a novel 2D layered polymer with a graphite-like array of silver (I) ions, with CH₃COO⁻ anion coordinated to silver(I) ions by O atom. Complex 5 shows a 3D diamond-like network structure constructed by the sulfur atom of 1,3-imidazolidine-2-thione ligand and Cl⁻ anions.     

Mineral Supported Facile Synthesis of Novel 4-Hydroxybenzoxazin-2-Thione N-Nucleosides

One-pot montmorillonite K-10 clay-supported reactions of substituted/unsubstituted salicylaldehyde and ribosyl/deoxyribosyl thioureas expeditiously yielded novel N-nucleosides, 4-hydroxy-3,4-dihydro-3-(β-D-ribofuranosyl or β-D-2 ′-deoxyribofuranosyl)-2 ^″-benz[e]-1,3-oxazin-2-thione via cycloisomerization of aldehyde intermediate under solvent-free microwave irradiation conditions.     

Inhibition of the D-fructose transporter protein GLUT5 by fused-ring glyco-1,3-oxazolidin-2-thiones and -oxazolidin-2-ones

The glucose transporter 5 (GLUT5)-a specific D-fructose transporter-belongs to a family of facilitating sugar transporters recently enlarged by the human genome sequencing. Prompted by the need to develop specific photolabels of these isoforms, we have studied the interaction of conformationally locked D-fructose and L-sorbose derived 1,3-oxazolidin-2-thiones and 1,3-oxazolidin-2-ones to provide a rational basis for an interaction model. The inhibition properties of the D-fructose transporter GLUT5 by glyco-1,3-oxazolidin-2-thiones and glyco-1,3-oxazolidin-2-ones is now reported. In vitro, the fused-rings systems tested showed an efficient inhibition of GLUT5, thus bringing new insights on the interaction of D-fructose with GLUT5.     

An Expeditious Synthesis of Benzoxazine-2-Thione c-Nucleosides Via Cu(OTf)2-Mediated Dehydrazinative β-Glycosylation

A novel expeditious synthetic protocol for 1,3-benzoxazine-2-thione C-nucleosides via Cu(OTf)₂-mediated dehydrazinative β-glycosylation of 4-hydrazino-2H-benz[e]-1,3-oxazine-2-thiones with unprotected D-ribose is reported.     

Synthesis of 1,3-Dithiane-2-thiones

A number of new 1, 3-dithiane-2-thione derivatives were synthesized from bismesylates of substituted 1, 3-dihydroxypropanes by the reaction with sodium trithiocarbonate provided from Na₂S and CS₂. The cyclic structures were elucidated on the basis of the IR, UV, NMR, and mass spectra, together with elemental analyses and chemical reactions.     

Synthesis and conformational analysis of 1,2-cis fused bicyclic α-d-galactofuranosyl thiocarbamate from per-O-tert-butyldimethylsilyl-β-d-galactofuranosyl isothiocyanate

Per-O-tert-butyldimethylsilyl-α,β-d-galactofuranosyl isothiocyanate (4) was synthesized by the reaction of per-O-TBS-β-d-galactofuranose (1) with KSCN, promoted by TMSI. Upon O-desilylation (1,2-dideoxy-α-d-galactofuranoso)[1,2d]-1,3-oxazolidine-2-thione (6), the cis-fused bicyclic thiocarbamate was obtained as the only product. Conformational analysis, aided by molecular modelling, showed two stable twist forms ((3)T(4) and (4)T(O)) for the five-membered sugar ring in 6. In aqueous solution, the equilibrium favours the first conformation (3:1 ratio). On the other hand, this ratio decreases for less polar solvents.     

Aromatic ring cleavage of a β-biphenyl ether dimer catalyzed by lignin peroxidase of phanerochaete chrysosporium

Under aerobic conditions homogeneous lignin peroxidase catalyzed the oxidation of 1-(4'-methoxyphenyl)-2-(2″,5′-dimethoxy-4″-phenylphenoxy)-1,3-dihydroxypropane (I) to yield four products: 1-(4'-methoxy-phenyl)-1,2,3-trihydroxypropane (X), 4-[-hydroxy--(4'-methoxyphenyl)-methyl]-1,3-dioxolane-2-one (V), 4-(4'-methoxyphenyl)-5-hydroxymethyl-1,3-dioxolane-2-one (VI) and 5-hydroxy-5-carbomethoxy-4-phenyl-oxol-3-en-2-one (VIII). V, VI and VIII are all products of ring opening reactions. When the reaction was conducted under anaerobic conditions, the substrate was oxidized but no ring-cleaved products were detected. During the oxidation of I, 4 atoms of ¹⁸O from ¹⁸O₂ were incorporated into the lactol product VIII.     

A computational approach to the synthesis of 1,3,5-thiadiazinane-2-thiones in aqueous medium: theoretical evidence for water-promoted heterocyclization

Based on experimental evidence and DFT studies, a probable cyclization route to 1,3,5-thiadiazinanes-2-thiones in aqueous medium is proposed. Experimental facts suggest the formation of a {[hydroxymethyl (substituted) carbamothioyl] sulfanyl}methanol intermediate via reaction of dithiocarbamate (DTC) and formaldehyde. Nucleophilic addition of glycine to this intermediate generates an adduct that undergoes intramolecular heterocyclization via an S_N2 reaction. Computational calculations predict an active role of water in the reaction mechanism that promotes intramolecular cyclization. Figure Energy profile of the proposed reaction mechanism for the synthesis of thiadiazinane-2-thione ring 11 in aqueous medium from a (hydroxymethylcarbamothioyl)sulfanylmethanol intermediate, 9     

Enzymatic asymmetrization of prochiral 2-benzyl-1,3-propanediol through esterification in solvent media

The enzymatic esterification of the prochiral substrate, 2-benzyl-1,3-propanediol, has been studied in solvent media. Among the five tested lipases, Lipozyme and Novozym 435 led to higher reaction rates. Novozym 435 catalyzed faster reactions at low water activity and in solvents having log P above 2. However, the two positions of the diol, pro-(R) and pro-(S), led to the same reaction rate trends and no prochiral selectivity was obtained. When using Lipozyme in toluene, the reaction rates for the formation of both (R) and (S) products presented an optimum at a water activity of 0.22. In this case, the prochiral selectivity increased with the water activity, from a value of 5 at a _w < 0.01, to a value of 8 at a _w = 0.22, at which point it remained constant.     

New Pyrimidine Cyclonucleosides with Hydrogenated Aglycones: Synthesis and X-Ray Structures

Abstract

Acid catalysed transformations of (6S)-6,5′-anhydro-6-hydroxy-1-(2′,3′-O-isopropylidene-β-D-ribofuranosyl)hexahydropyrimidine-2-thione are studied. (6R)-6,2′-anhydro-6-hydroxy-1-(α-D-ribofuranosyl)hexahydropyrimidine-2-thione was formed as a thermodynamically stable product. Two intermediates, (6S)-6,5′-anhydro-6-hydroxy-1-(β-D-ribofuranosyl)hexahydropyrimidine-2-thione and 6-hydroxy-1-(D-ribosyl)hexahydropyrimidine-2-thione and products of cleavage of glycosidic bond were identified in the reaction mixtures. Results of X-ray structural determination of the synthesised nucleosides are presented.     

Temperature-dependence of enantioselectivity and desymmetrization in the acetylation of 2-mono- and 2,2-di-substituted 1,3-propanediols by a novel lipase isolated from the yeast Cryptococcus spp. S-2

The effect of temperature on enantioselectivity and desymmetrization in the acetylation of 2-phenyl-1,3-propanediol (1a), 2-benzyl-1,3-propanediol (1b), 2-methyl-2-phenyl-1,3-propanediol (1c) and 2-benzyl-2-methyl-1,3-propanediol (1d) by a novel lipase (CSL) isolated from the yeast Cryptococcus spp. S-2 was studied. Desymmetrization of 1a, 1c and 1d by CSL-catalyzed acetylation was observed in the temperature range of ?20°C to 40°C, while diacetylation of 1b occurred considerably even at 0°C. The kinetic parameters of the selectivity indicated that the acetylation of 1a is an entropy controlled process whereas the reaction of 1c and 1d is mainly controlled by the enthalpy term. In the monoacetylation of the diol 1d, the preferred configuration in the enantiomeric induction by CSL was opposite to that of immobilized porcine pancreatic lipase (PPL).     

Synthesis, structure and reactivity of 5-pyranosyl-1,3,4-oxathiazol-2-ones

5-(1,2,3,4-tetra-O-acetyl-alpha-D-xylopyranos-5S-C-yl)-1,3,4-oxathiazol-2-one (8) has been prepared from glucuronamide in two steps and 73% overall yield by conversion to the tetra-O-acetyl derivative 7 followed by reaction with chlorocarbonylsulfenyl chloride. 5-(2,3,4-Tri-O-acetyl-beta-D-xylopyranosyl)-1,3,4-oxathiazol-2-one (12) was synthesised from D-xylose by a four-step sequence involving conversion to the xylopyranosylnitromethane derivative 9, reaction with PCl3 to afford nitrile 10, hydrolysis to amide 11, and finally treatment with ClCOSCl. D-glucose-derived analogue 13 was prepared similarly. The structure of oxathiazolone 8 was established by X-ray crystallography. Thermolysis of the oxathiazolones 8 and 12 at 130-160 degrees C resulted in decarboxylation and desulfuration to yield the corresponding nitriles. Attempts to trap the putative nitrile sulfide intermediates by repeating the thermolysis in the presence of dipolarophiles, such as ethyl cyanoformate, afforded only traces of the 1,3-dipolar cycloadducts; however, under microwave irradiation oxathiazolone 8 and ethyl cyanoformate afforded ethyl 3-(1,2,3,4-tetra-O-acetyl-alpha-D-xylopyranos-5S-C-yl)-1,2,4-thiadiazole-5-carboxylate 22 in good yield.     

High-performance liquid chromatographic determination of 1,3-diethyl-2-thiobarbituric acid–malonaldehyde adduct in fish meat

The reaction conditions of 1,3-diethyl-2-thiobarbituric acid (DETBA)–malonaldehyde (MA) adduct formation were examined in order to analyze MA in fish tissue by high-performance liquid chromatography. A reaction mixture containing 4 mM butyl hydroxytoluene was heated at 100°C for 150 min and the DETBA–MA adduct formed was separated by a Inertsil ODS column for 20 min. The detection limit was 5 pmol.     

From linden flower to linden honey. Part 2: Glycosidic precursors of cyclohexa-1,3-diene-1-carboxylic acids

The presence of two unusual, recently identified terpene acids, i.e., 4-(1-hydroxy-1-methylethyl)cyclohexa-1,3-diene-1-carboxylic acid (1) and 4-(1-methylethenyl)cyclohexa-1,3-diene-1-carboxylic acid (2), was now also confirmed in (Swiss) linden honey, after solid-phase extraction and HPLC purification. NMR Spectroscopy, in combination with UPLC/MS analysis, showed the presence of several glycosides of 1, which accounted for ca. 0.6 weight-% of the honey, as quantified by UPLC-UV. The major 'glycoside' of 1, compound 5, could be isolated and identified by 2D-NMR experiments as the corresponding beta-gentiobiosyl ester (rather than the classical compound with a glycosidic bond between an aglycone OH group and the sugar). The same diglycosides found in linden honey were also detected in linden nectar; also, chestnut and fir honeys contained these glycosides in minor quantities, but not colza, acacia, or dandelion honeys (Table 2).     

Mineral supported facile synthesis of novel 4-hydroxybenzoxazin-2-thione N-nucleosides

One-pot montmorillonite K-10 clay-supported reactions of substituted/unsubstituted salicylaldehyde and ribosyl/deoxyribosyl thioureas expeditiously yielded novel N-nucleosides, 4-hydroxy-3,4-dihydro-3-(beta-D-ribofuranosyl or beta-D-2'-deoxyribofuranosyl)-2'-benz[e]-1,3-oxazin-2-thione via cycloisomerization of aldehyde intermediate under solvent-free microwave irradiation conditions.     

The reactions of the hydroxymethyl radical with 1,3-dimethyluracil and 1,3-dimethylthymine

Hydroxymethyl radicals .CH2OH, generated by the radiolysis of methanol (0.5 mol dm-3) in N2O-saturated aqueous solutions, were reacted with 1,3-dimethyluracil or 1,3-dimethylthymine (10(-3) mol dm-3). The products were identified and their G values determined. It has been concluded that in 1,3-dimethyluracil .CH2OH attack occurs only at C(6) while in 1,3-dimethylthymine there is partitioning between addition (two-thirds) and H-abstraction from the C(5)-methyl group (one-third). A rate constant for CH2OH addition to 1,3-dimethyluracil of about 10(4) dm3 mol-1 s-1 is estimated. Complexities that may arise in the radiolysis of pyrimidines such as 1,3-dimethylthymine, apparently as a consequence of the formation of 5-alkylidenepyrimidines, are discussed. A value of 0.15 has been estimated for the disproportionation/combination ratio for the hydroxymethyl radical self-termination reaction.     

2-Aryl-1,3-thiazolidines as masked sulfhydryl agents for inhibition of melanogenesis

As a part of an ongoing project aimed at developing new skin depigmenting agents, the ability of variously substituted 2-aryl-1,3-thiazolidines to inhibit melanogenesis in vitro was investigated. At 0.2 mM concentration 2-(2'-hydroxyphenyl)-1,3-thiazolidine-4-carboxylic acid (Th2), as well as the descarboxy analog (Th1) and, to a lower extent, the 4'-hydroxy isomer (Th3) all proved capable of preventing the tyrosinase catalyzed conversion of 0.2 mM L-tyrosine to melanin. Spectrophotometric monitoring of the reaction course in the presence of Th2 showed the initial formation of a yellow chromophore (lambda max 400 nm) which slowly decayed, being eventually replaced by a new absorption maximum centered at 305 nm. HPLC analysis of the final incubation mixture revealed the presence of a major product (lambda max 306 nm), ninhydrin and ferric chloride positive, which was isolated by gel filtration on Sephadex G-10 and was identified as beta-[7-(3-carboxy-5-hydroxy-3,4-dihydro-2H-1,4-benzothiazinyl)]al anine (DBA) by 1H-NMR spectroscopy. Attempts to isolate the intermediate with lambda max 400 nm were hampered by its marked instability under the usual chromatographic conditions. However, the nature of the chromophore, coupled with mechanistic considerations, suggested for the compound the Schiff base-containing structure 3,4-dihydroxy-5-S-(N-salicylidenecysteinyl)phenylalanine (salcysdopa). This was substantiated by: (i) the formation of a zinc complex (lambda max 349 nm) analogous to that observed with the model Schiff base N-salicylidene leucine; and (ii) detection by 1H-NMR of a Schiff base resonance at delta 8.1 during the yellow chromophoric phase of the reaction. It was concluded that 1,3-thiazolidines inhibit melanin formation by a mechanism that involves the trapping of enzymically generated dopaquinone by the -SH containing Schiff base arising by cleavage of the thiazolidine ring. The salcysdopa adduct thus formed undergoes hydrolysis and subsequent ring closure to give eventually the colorless DBA.     

Synthesis of novel chiral Cu or Ag/S,N cluster complexes and absolute stereostructures as determined by x-ray crystallography

Novel chiral copper(I) and silver(I) metal complexes were synthesized from the reaction of chiral 1,3-thiazolidine-2-thione ligand with CuCl and AgOAc in dichloromethane in the presence of Et(3)N and DMAP at room temperature. Their unique crystal structures were determined by X-ray analysis. Four Cu(I) atoms and four 1,3-thiazolidine-2-thione ligands form a butterfly-type metal cluster. Six Ag(I) atoms and six 1,3-thiazolidine-2-thione ligands form another butterfly-type cluster.     

A green expedient synthesis of pyridopyrimidine-2-thiones and their antitubercular activity

The pseudo four-component domino reactions of N-substituted-4-piperidones, substituted aromatic aldehydes and thiourea in the presence of solid sodium ethoxide under solvent-free conditions afforded pyridopyrimidine-2-thiones in almost quantitative yields by simply grinding for 1-2 min. at ambient temperature. The synthesized compounds were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv. Among them, (E)-6-benzyl-8-(2,4-dichlorobenzylidene)-4-(2,4-dichlorophenyl)-3,4,5,6,7,8-hexahydropyrido[4,3-d]pyrimidine-2(1H)-thione (MIC 2.8 μM) displays the maximum activity, being 2.7 and 1.7 times more active than the first line antitubercular drugs ethambutol and ciprofloxacin, respectively, and less active than rifampicin and isoniazid, by 28 and 7 times, respectively.