Supported synthesis and functionnalization of 2'-deoxyuridine by Suzuki-Miyaura cross-coupling

The synthesis and modification of 2'-deoxyuridine has been realized under Suzuki-Miyaura palladium-catalyzed cross-coupling conditions. Using Pd(PPh(3))(4) and Na(2)CO(3), 5-iodo-2'-deoxyuridine bound to solid support is coupled with various boronic acids to give 5-(hetero)aryl-2'-deoxyuridine. Pd(PPh(3))(4) palladium catalyzed was found to be superior to Pd(OAc)(2) and (NHC)Pd(allyl)Cl for Suzuki-Miyaura palladium-catalyzed reactions.     

Self-assembly of cationic palladium complexes by redistribution of pyridine ligands

The reaction of [Pd(OAc)₂(py)₂] with [Li((OEt₂)_2.5)][B(C₆F₅)₄] was conducted with intent to generate the cationic palladium complex [Pd(OAc)(py)₃][B(C₆F₅)₄], (2, py = pyridine). A single crystal structure of this material, however, reveals a 1-D polymer structure formed by the self-assembly of alternating dicationic ([Pd(py)₄]²⁺) and neutral ([Pd(OAc)₂(py)₂]) palladium units bridged by acetato linkages to give [Pd(py)₄][Pd(OAc)₂(py)₂][B(C₆F₅)₄]₂ (3). These two palladium sites are produced by disproportionation of the pyridine ligands in [Pd(OAc)(py)₃][B(C₆F₅)₄]. Proton NMR studies confirm the existence of a solvent dependent equilibrium between [Pd(py)₄]²⁺, [Pd(OAc)₂(py)₂] and [Pd(OAc)(py)₃]⁺.     

mt-tRNA Components: Synthesis of (2-Thio)Uridines Modified with Blocked Glycine/Taurine Moieties at C-5,1

In this paper, we discuss the usefulness of reductive amination of 5-formyl-2′,3′-O-isopropylidene(-2-thio)uridine with glycine or taurine esters in the presence of sodium triacetoxyborohydride (NaBH(OAc)₃) for the synthesis of the native mitochondrial (mt) tRNA components 5-carboxymethylaminomethyl(-2-thio)uridine (cmnm⁵(s²)U) and 5-taurinomethyl(-2-thio)uridine (τm⁵(s²)U) with a blocked amino acid function. 2-(Trimethylsilyl)ethyl and 2-(p-nitrophenyl)ethyl esters of glycine and 2-(2,4,5-trifluorophenyl)ethyl ester of taurine were selected as protection of carboxylic and sulfonic acid residues, respectively. The first synthesis of 5-formyl-2′,3′-O-isopropylidene-2-thiouridine is also reported.     

Synthesis of polystyrene microspheres and functionalization with Pd(0) nanoparticles to perform bioorthogonal organometallic chemistry in living cells

We have developed miniaturized heterogeneous Pd(0)-catalysts (Pd(0)-microspheres) with the ability to enter cells, stay harmlessly within the cytosol and mediate efficient bioorthogonal organometallic chemistries (e.g., allylcarbamate cleavage and Suzuki-Miyaura cross-coupling). This approach is a major addition to the toolbox available for performing chemical reactions within cells. Here we describe a full protocol for the synthesis of the Pd(0)-microspheres from readily available starting materials (by the synthesis of size-controlled amino-functionalized polystyrene microspheres), as well as for their characterization (electron microscopy and palladium quantitation) and functional validation ('in solution' and 'in cytoplasm' conversions). From the beginning of the synthesis to functional evaluation of the catalytic device requires 5 d of work.     

Interaction of sesamol (3,4-methylenedioxyphenol) with tyrosinase and its effect on melanin synthesis

Sesamin, sesamolin (lignans) and sesamol - from sesame seed (Sesamum indicum L.) - are known for their health promoting properties. We examined the inhibition effect of sesamol, a phenolic degradation product of sesamolin, on the key enzyme in melanin synthesis, viz. tyrosinase, in vitro. Sesamol inhibits both diphenolase and monophenolase activities with midpoint concentrations of 1.9 μM and 3.2 μM, respectively. It is a competitive inhibitor of diphenolase activity with a K_i of 0.57 μM and a non-competitive inhibitor of monophenolase activity with a K_i of 1.4 μM. Sesamol inhibits melanin synthesis in mouse melanoma B16F10 cells in a concentration dependant manner with 63% decrease in cells exposed to 100 μg/mL sesamol. Apoptosis is induced by sesamol, limiting proliferation. This study of the chemistry and biology of lignans, in relation to the mode of action of bioactive components, may open the door for drug applications targeting enzymes.     

Reaction of ethyl 2-amino-4,6-O-benzylidene-2-deoxy-d-gluconate with acetylenic esters

Ethyl 2-amino-4,6-O-benzylidene-2-deoxy-d-gluconate adds to acetylenic esters to give sugar enaminones. The following acetylene derivatives have been employed: methyl propiolate, ethyl phenylpropiolate, and dimethyl acetylenedicarboxylate (6). With compound 6, the reaction leads to a mixture of the expected enaminone and the isomeric oxazolidine derivative. The structures and configurations of the new compounds were studied by spectroscopic and chemical methods.     

Palladium-catalyzed oxidation of benzylated aldose hemiacetals to lactones

Benzyl protected sugar hemiacetals are oxidized to the corresponding lactones in excellent yields using bromobenzene, K(2)CO(3) and the Pd(OAc)(2)/PPh(3) catalytic system.     

New Pd(II) and Pt(II) complexes with N,S-chelated pyrazolonate ligands: molecular and supramolecular structure and preliminary study of their in vitro antitumoral activity

New Pd(II) and Pt(II) complexes [ML2] (HL=a substituted 2,5-dihydro-5-oxo-1H-pyrazolone-1-carbothioamide) have been synthesized by reacting K2MCl4 (M=Pd, Pt) or Pd(OAc)2 with beta-ketoester thiosemicarbazones. The structures of seven of these complexes were determined by X-ray diffraction. Although all exhibit a distorted square-planar coordination with trans- or (in one case) cis-[MN2S2] kernels, their supramolecular arrangements vary widely from isolated molecules to 3D-networks. The in vitro antitumoral assays performed with two HL ligands and their metal complexes showed significant cytostatic activity for the latter, with the most active [ML2] derivative (a palladium complex) being about sixteen times more active than cis-DDP against the cisplatinum-resistant cell line A2780cisR.     

Capsaicinol: synthesis by allylic oxidation and its effect on TRPV1-expressing cells and adrenaline secretion in rats

Capsaicinol is an ingredient of hot red pepper. In this study, we developed a novel method for capsaicinol synthesis and examined capsaicinol's physiological effects on capsaicin receptor (TRPV1)-related actions. Allylic oxidation of capsaicin by palladium acetate (Pd(OAc)(2)) resulted in the formation of (+/-)-capsaicinol acetate at a 7.2% yield in a single step. The effectiveness of (+/-)-capsaicinol in TRPV1 activation (EC(50)=1.1 microM) was found to be weaker than that of capsaicin (EC(50)=0.017 microM), whereas the efficacy of (+/-)-capsaicinol reached 75% of that of capsaicin. Intravenous administration of (+/-)-capsaicinol in anesthetized rats dose-dependently enhanced adrenaline secretion from the adrenal gland. The response to a 5 mg/kg-dose of (+/-)-capsaicinol was comparable to that of a 0.05 mg/kg-dose of capsaicin. The relative pungency of capsaicinol to capsaicin was coincident with the relative effectiveness in inducing these TRPV1-related actions.     

Use of the 2-(4-Pyridyl)Ethyl Protecting Group in the Synthesis of DNA Fragments Via Phosphoramidite Intermediates

Abstract

2-(4-Pyridyl)ethyl is a new protecting group for the internucleotidic bonds in the synthesis of deoxyribooligonucleotides by the phosphoramidite approach. This group is stable to alkali and acid conditions, and can be removed easily by two step procedures under mild conditions. The synthesis of deoxyribo-oligonucleotides by using phosphoramidite units containing 2-(4-pyridyl)ethyl group is also described.     

Synthesis of fluorinated carbazoles via C–H arylation catalyzed by Pd/Cu bimetal system and their antibacterial activities

An effective intramolecular C–H arylation reaction catalyzed by a bimetallic catalytic system Pd(OAc)₂/CuI for the synthesis of fluorine-substituted carbazoles from corresponding N-phenyl-2-haloaniline derivatives under ligand free conditions is demonstrated. The established method is effective for both N-phenyl-2-bromoaniline and N-phenyl-2-chloroaniline, and requires the low loading of Pd(OAc)₂ (0.5 mol %). A series of new fluorinated carbazoles were synthesized in excellent yields using the protocol (>83%, 19 examples) and were fully characterized by ¹H, ¹³C and ¹⁹F NMR spectral data, HRMS and elemental analysis. All compounds were evaluated for their antibacterial activities against four bacteria (Bacillus subtilis, Staphylococcus aureus, Escherichia coli and methicillin-resistant S. aureus with resistance to gentamicin) by serial dilution technique. All tested compounds showed antibacterial activity against three test strains (S. aureus, B. subtilis and MRSA), and most of these compounds displayed pronounced antimicrobial activities against these three strains with low MIC values ranging from 0.39 to 6.25 μg/mL. Among them, compounds 7 and 14 exhibited potent inhibitory activity better than reference drugs meropenem and streptomycin. Three compounds (2, 4 and 5) showed antibacterial activity against E. coli. with MIC values from 12.5 to 25 μg/mL.     

Sesamol as a potential radioprotective agent: in vitro studies

Protection against radiation-induced DNA strand breaks is an important aspect in the design and development of a radioprotector. In this study, the radioprotective efficacy of sesamol, a natural antioxidant, was investigated in aqueous solution of plasmid DNA (pBR322) and compared with that of melatonin, a known antioxidant-based radioprotector. Thermal denaturation studies on irradiated calf thymus DNA were also carried out with sesamol and melatonin. Sesamol demonstrated greater radioprotective efficacy in both plasmid DNA and calf thymus DNA. To assess the radical scavenging capacity of sesamol and melatonin, 2-deoxyribose degradation, DPPH and ABTS assays were performed. Sesamol exhibited more scavenging capacity compared to melatonin. In vitro studies with V79 cells showed that sesamol is 20 times more potent than melatonin. It is proposed that the greater radioprotective efficacy of sesamol could be due to its greater capacity for scavenging of free radicals compared to melatonin. The results will be helpful in understanding the mechanisms and development of sesamol as a radioprotector.     

Binding properties and stoichiometries of a palladium(II) complex to metallothioneins in vivo and in vitro

This paper will be the first to discuss the in vivo and in vitro properties of a Pd(II) complex, K2PdCl4, interacting with metallothioneins (MTs). In vivo experiments revealed that intraperitoneal injections of K2PdCl4 into rabbits led to the simultaneous synthesis of Pd-MT in the kidney and Zn7MT in the liver. The renal Pd-MT complex contains 3.6 +/- 0.3 Pd, 2.1 +/- 0.2 Zn, and 1.0 +/- 0.1 Cu per mole protein. It was found that pre-treatment with Zn(NO3)2 before K2PdCl4 injections significantly enhanced renal Pd-MT level. The same pre-treatment also increases hepatic Zn-MT levels. These results strongly suggest that Pd(II) ions can be bound in vivo by MT existing in the rabbit kidneys to form Pd-MT. Gel-filtration chromatographic studies after the incubation of either native Cd5Zn2MT2 or Zn7MT2 with K2PdCl4 in vitro demonstrate that Pd(II) ions promote the non-oxidative oligomerization of native MTs. Increasing the level of Pd(II) relative to MT led to a concomitant increase in the apparent yield of MT oligomers. At relatively low Pd-MT ratio, Pd(II) is found predominantly in the oligomers while the monomeric products are chiefly composed of the reactants, Cd5Zn2MT2 or Zn7MT2. Based on our experimental data, the mechanisms of the reactions between Pd(II) and MTs in vivo and in vitro are discussed.     

Enrichment,isolation and characterization of fungi tolerant to 1‐ethyl‐3‐methylimidazolium acetate

Aims: This work aimed to characterize microbial tolerance to 1‐ethyl‐3‐methylimidazolium acetate ([C2mim][OAc]), an ionic liquid that has emerged as a novel biomass pretreatment for lignocellulosic biomass. Methods and Results: Enrichment experiments performed using inocula treated with [C2mim][OAc] under solid and liquid cultivation yielded fungal populations dominated by Aspergilli. Ionic liquid‐tolerant Aspergillus isolates from these enrichments were capable of growing in a radial plate growth assay in the presence of 10% [C2mim][OAc]. When a [C2mim][OAc]‐tolerant Aspergillus fumigatus strain was grown in the presence of switchgrass, endoglucanases and xylanases were secreted that retained residual enzymatic activity in the presence of 20% [C2mim][OAc]. Conclusions: The results of the study suggest that tolerance to ionic liquids is a general property of the Aspergilli. Significance and Impact of the Study: Tolerance to an industrially important ionic liquid was discovered in a fungal genera that is widely used in biotechnology, including biomass deconstruction.     

Graphite catalyzed solvent free synthesis of dihydropyrimidin-2(1H)-ones/thiones and their antidiabetic activity

A solvent free three component condensation reaction between an aldehyde, ethyl acetoacetate and urea catalyzed by graphite, a green catalyst is described for the synthesis of dihydropyrimidin-2(1H)-ones. This protocol is scalable and the catalyst is reusable. This method is also applied for the synthesis of dihydropyrimidin-2(1H)-thiones. α-Amylase, a key enzyme in carbohydrate metabolism is generally targeted for management of type 2 diabetes. The therapeutic potential of the dihydropyrimidinones and dihydropyrimidinthiones to inhibit α-amylase activity was evaluated by in vitro assay. Of the synthesized compounds 3,4-dihydropyrimidin-2(1H)-thione (1k) demonstrated highest inhibition of α-amylase activity.     

Palladium-catalyzed multi-component synthesis of steroidal A- and D-ring fused 5,6-disubstituted pyridines under microwave irradiation

The preparation of steroidal A-, D-ring fused 5,6-disubstituted pyridines and nonsteroidal substituted pyridines is described form Pd(OAc)₂ catalyzed multi-component reaction of steroidal/nonsteroidal β-halovinyl aldehyde, alkyne and benzylamine in solvent-free condition under microwave irradiation.     

Nano Pd(0) supported on cellulose: a highly efficient and recyclable heterogeneous catalyst for the Suzuki coupling and aerobic oxidation of benzyl alcohols under liquid phase catalysis

Nano palladium(0) supported on cellulose was found to be highly efficient recyclable heterogeneous catalyst for the Suzuki coupling between aryl bromides and phenyl boronic acid in water and aerobic oxidation of benzyl alcohols using air as the source of molecular oxygen in acetonitrile. The Cell-Pd(0) was prepared by stirring commercially available cellulose with Pd(OAc)₂ in ethanol at 25 °C followed by reduction with hydrazine hydrate, leading finally to nano Pd(0) particles uniformly distributed on surface of cellulose. This catalytic system provides biaryls and polyaryls in excellent yields with very high turn over numbers via Suzuki coupling; and benzaldehyde derivatives in high yields and selectivity by oxidation in air. Cell-Pd(0) was characterized by X-ray diffraction techniques (XRD), thermal analysis (TGA), scanning electron microscope (SEM) and transmission electron microscope (TEM).     

The first pincer-aryl [M-(NCN)] complexes {M = Pd(II); Pt(II)} with chiral pyridine donors: Synthesis and catalytic activity in C-C bond formation

The first chiral bis(pyridine) N-C(H)-N pincer ligand, (5S,7S)-1,3-bis(6,6-dimethyl-5,6,7,8-tetrahydro-5,7-methanquinolin-2-yl)benzene (HL) has been synthesized and characterized by a thorough ¹H NMR analysis. Reaction of HL with K₂[PtCl₄] in acetic acid gives [Pt(L)Cl] (1), where L acts as a tridentate N-C-N pincer ligand. The analogous palladium(II) derivatives [Pd(L)Cl] (2), and [Pd(L)(OAc)] (3), were first prepared through a transmetalation reaction between Pd(OAc)₂ and the organomercury compound [Hg(L)Cl] (4). The structures of compounds 1 (Pt) and 2 (Pd), as determined by X-ray diffraction, are reported and compared. Compound 2 can also be obtained from Na₂[PdCl₄] and HL in refluxing acetic acid, i.e., under the same conditions used for compound 1. Apparently, this is the first palladium pincer derivative of a 1,3-bis(pyridyl)benzene ligand synthesized by direct C-H activation.The neutral complexes 1-3 are catalysts of modest activity, but devoid of enantioselectivity in the Heck reaction between iodobenzene and methyl acrylate and in the aldol condensation of benzaldehyde with methyl isocyanoacetate.     

Decreased production of interleukin-6 and prostaglandin E2 associated with inhibition of delta-5 desaturation of omega6 fatty acids in mice fed safflower oil diets supplemented with sesamol

The differences in the immune responses in mice fed sesame oil diets and those fed sesamin may be attributed to the presence of other lignans in the non-fat portion of the oil. The fatty acid composition (mean +/- SD mol. %) of liver membrane phospholipids and the levels of endotoxin-induced prostaglandin (PG) E2, interleukin (IL)-6, IL-10, IL-12 and tumor necrosis factor (TNF)-alpha were determined in mice fed diets supplemented with 5% safflower oil (SO) in the absence or presence of 1% sesamol. The levels of dihomo-gamma-linolenic acid (20:3omega6) were markedly higher (P<0.025) in the livers from mice fed sesamol supplemented SO diets (1.6 +/- 0.1) compared to the controls (1.4 +/- 0.1). These data suggest that sesamol or its metabolite could inhibit the in vivo delta-5 desaturation of omega6 fatty acids. Further, in animals fed sesamol supplemented SO diets, the levels of PGE2 (228 +/- 41 pg/ml) were markedly lower (P<0.01) compared to those fed SO diet alone (1355 +/- 188 pg/ml). Concomitantly, the concentrations of IL-6 were also lower (P<0.01) in mice fed sesamol diet (63 +/- 11 ng/ml) compared to the controls (143 +/- 22 ng/ml). A marked reduction in the levels of PGE2 in animals fed sesamol diets suggests that sesamol or its metabolite could inhibit the activity of cyclooxygenase enzyme.     

Palladium(II) complexes of a bis-2-aminobiphenyl N-heterocyclic carbene: Synthesis, structural studies and catalytic activity

A new imidazolinium [(SIBiphen)H](BF₄) was synthesized in three steps from 2-aminobiphenyl. The reaction of the salt with Pd(OAc)₂, NaI and t-BuOK gave a dimeric Pd(II) complex [(SIBiphen)PdI₂]₂, which was analyzed by an X-ray diffraction study. The reaction of [Pd(allyl)Cl]₂, the imidazolinium salt and t-BuOK in THF at −78 °C gave the monomeric Pd complex, in which the N-heterocyclic carbene was bound to the metal centre, as confirmed by a single-crystal X-ray diffraction study. A preliminary catalytic study showed that these new systems were moderately active in the Suzuki-Miyaura coupling of aryl halides.