The Henry reaction of (1R)-(1,4:3,6-dianhydro-d-mannitol-2-yl)-1,4:3,6-dianhydro-d-fructose 5,5′-dinitrate. Different reactive features of nitromethane to nitroethane

Henry reactions of a novel higher sugar derivative, (1R)-(1,4:3,6-dianhydro-d-mannitol-2-yl)-1,4:3,6-dianhydro-d-fructose 5,5′-dinitrate (Alternate nomenclature: (1R)-(isomannid-2-yl)-1,4:3,6-dianhydro-d-fructose 5,5′-dinitrate), with nitromethane and nitroethane were studied. The kinetic and thermodynamic reactions with nitromethane under different conditions were carried out to afford (2S)- and (2R)-β-nitroalcohols, respectively. But when using nitroethane the reaction gave a (2S)-β-nitroalcohol with an inverted configuration at vicinal carbon C-1. Two stereogenic centers were generated, and one was altered in the reaction.     

Facile route for the synthesis of the iminosugar nucleoside (3R,4R)-1-(pyren-1-yl)-4-(hydroxymethyl)pyrrolidin-3-ol

N-(Pyren-1-yl)-(3R,4S)-4-[(1S,2R)-1,2,3-trihydroxypropyl]pyrrolidin-3-ol (4) was obtained in 36% yield from 3-deoxy-3-C-formyl-1,2:5,6-di-O-isopropylidene-α-d-allofuranose (3) by combined hydrolysis and aminoalkylation reactions with 1-aminopyrene in a one-pot reaction. Cleavage reactions of the exocyclic triol chain in 4 with NaIO₄ and NaBH₄ resulted in iminosugars 7 and 8, which are analogues of the furanose forms of 2-deoxy-d-allose and of 2-deoxy-d-ribose, the latter analogue N-(pyren-1-yl)-(3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol (8) being formed in 83% yield.     

Synthesis of long-chain fatty acid derivatives as a novel anti-Alzheimer’s agent

In order to develop new drugs for Alzheimer’s disease, we prepared 17 fatty acid derivatives with different chain lengths and different numbers and positions of double bonds by using Wittig reaction and stereospecific hydrogenation of triple bonds as key reactions. Among them, (4Z,15Z)-octadecadienoic acid (10) and (23Z,34Z)-heptatriacontadienoic acid (16) showed the most potent neurite outgrowth activities on Aβ(25–35)-treated rat cortical neurons, which activities were comparable to that of a positive control, NGF. Both fatty acids 10 and 16 possess two (Z)-double bonds at the n-3 and n-14 positions, which might be important for the neurite outgrowth activity.     

Melanogenesis inhibition by tetrahydropterines

There is controversy in the literature concerning the action of tetrahydropterines on the enzyme tyrosinase and on melanogenesis in general. In this study, we demonstrate that tetrahydropterines can inhibit melanogenesis in several ways: i) by non-enzymatic inhibition involving purely chemical reactions reducing o-dopaquinone to L-dopa, ii) by acting as substrates which compete with L-tyr and L-dopa, since they are substrates of tyrosinase; and iii) by irreversibly inhibiting the enzymatic forms met-tyrosinase and deoxy-tyrosinase in anaerobic conditions. Three tetrahydropterines have been kinetically characterised as tyrosinase substrates: 6-R-L-erythro-5,6,7,8-tetrahydrobiopterin, 6-methyl-5,6,7,8-tetrahydropterine and 6,7-(R,S)-dimethyl-5,6,7,8-tetrahydropterine. A kinetic reaction mechanism is proposed to explain the oxidation of these compounds by tyrosinase.     

Modification of polysaccharides containing uronic acid residues

Klebsiella Type 47 capsular polysaccharide has side chains attached to the main chain viaD-glucuronic acid residues. The side chains have been removed to yield an essentially linear polysaccharide by the following sequence of reactions: (1) substitution of hydroxyl and car?yl groups with methyl vinyl ether; (2) β-elimination by treatment with base; (3) removal of modified uronic acid residues and protecting groups by mild acid hydrolysis. The possibility of modifying other uronic acid-containing polysaccharides by this method is discussed.     

Bovine babesiosis and anaplasmosis: Control by premunition and chemoprophylaxis

Experiments were carried out to evaluate two systems: (1) premunition and (2) chemoprophylaxis for the control of bovine babesiosis and anaplasmosis in the Cauca River Valley, Colombia. Control of these diseases was achieved by inoculating cattle with virulent Babesia bigemina, Babesia argentina, and Anaplasma marginale and subsequent treatment with Imidocarb and Gloxazone to moderate the postpremunition reactions. Chemoprophylactic treatment with Imidocarb and Gloxazone was administered to cattle before and during field exposure. Premunized cattle were highly resistant to tick-borne (Boophilus microplus) challenge. Imidocarb had therapeutic and chemoprophylactic properties against babesiosis, but appeared toxic. Gloxazone moderated the A. marginale postpremunition reaction, but failed to prevent clinical anaplasmosis under the conditions of this investigation.     

Oxidation and keto reduction of 12-hydroxy-5,8,10,14-eicosatetraenoic acids in bovine corneal epithelial microsomes

The R and S enantiomers of 12-hydroxyeicosatetraenoic acid (12-HETE) exhibit different biological activities. Although they appear to be produced by different enzymatic pathways, cytochrome P-450 monooxygenase and lipoxygenase, respectively, they display similar metabolism in both corneal epithelium and neutrophils. In corneal epithelial microsomes, both enantiomers are subject to oxidation and keto reduction reactions to form the dihydro metabolite, 12-hydroxy-5,8,14-eicosatrienoic acid (12-HETrE), via a keto intermediate. The apparent K_m for the formation of 12-HETrE was 17.9 and 20 μM for 12(R)-HETE and 12(S)-HETE, respectively, and the apparent V_max of the reaction was 17.4 and 8.2 pmol/mg per min, respectively. Chiral analysis of the dihydro metabolite demonstrated a product enantiospecificty. Arachidonic acid, 12(R)-HETE, 12(S)-HETE and the intermediate of this reaction, 12-oxo-ETrE, were metabolized predominantly to 12(R)-HETrE in a ratio [12(R)-HETrE: 12(S)-HETrE] of 7.3:1, 4.3:1, 1.5:1 and 2.3:1, respectively. 12(R)-HETrE is a potent vasodilator, chemotactic and angiogenic factor whose synthesis is induced in inflamed tissues; 12(S)HETrE is devoid of these properties. 12(R)-HETE, derived from NADPH-dependent cytochrome P-450 monooxygenases, and 12(S)-HETE, derived from 12-lipoxygenase, may both play an important role in regulating the inflammatory response by serving as substrates for the local synthesis of 12(R)-HETrE.     

Nucleosides LXXXIII. Synthetic studies on nucleoside antibiotics. 11. Synthesis of methyl 4-amino-3,4-dideoxy-β-D-ribo-hexopyranoside and -hexopyranosiduronic acid (derivatives related to the carbohydrate moiety of gougerotin)

Methyl 4-amino-3,4-dideoxy-β-D-ribo-hexopyranoside (17) and its uronic acid (19) were synthesized via a series of reactions starting from 1,2:5,6-di-O-isopropylidene-3-O-tosyl-α-D-glucofuranose. A method suitable for the large scale preparation of 3,4-dideoxy- 1,2:5,6-di-O-isopropylidene-α-D-erythro-hex-3-enofuranose(2) was devised.     

Investigation of one-enzyme systems in the ω-transaminase-catalyzed synthesis of chiral amines

ω-Transaminase (TA) catalyzed asymmetric syntheses of amines were carried out in the one enzyme systems with wild-type enzymes (S)-TA from Pseudomonas aeruginosa, (S)-TA from Paracoccus denitrificans and (R)-TA from Aspergillus terreus. The scope of amine donors and aromatic carbonyl substrates was thoroughly explored. Among the range of potential amino donors, 2-propylamine, 2-butylamine and 1-phenylethylamine were found as promising candidates, which gave superior conversions in the amination reactions compared to other donors. Various prochiral aromatic ketones were accepted as substrates by the investigated enzymes. In most cases, good to excellent conversions (up to 98%) to the amine products with excellent e.e.-values (>99.9% for (S) or (R)) were obtained by the action of a single enzyme and an appropriate amino donor. (S)-TA from Paracoccus denitrificans was found to accept bulky ketones, e.g. 1-indanone, α- and β-tetralone or 2-acetonaphthone, in the asymmetric amination. In some cases the enantiomeric excesses in the amination reactions were dependent on the amino donor. Moreover, the influence of the pH, temperature and cosolvents on the outcome of reactions was additionally investigated.     

Syntheses of some purine nucleosides by the fusion method,by the condensation of acetylated chlorides,and from 1-acetates in the presence of titanium tetrachloride: a comparison

9-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)-6-benzamidopurine (9) and 6-benzamido-9-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)purine (11) have been prepared by three synthetic routes: (a) the fusion procedure, (b) direct condensation of 6-benzamido(chloromercuri)purine with the acetylated chloride, or (c) with the chloride formed in situ from the 1-acetate in the presence of titanium tetrachloride. The results obtained are briefly discussed; the direct condensation of the mercuri salt with chlorides proved to be the most convenient.Whereas, in the condensation with acetylated chlorides, only products having the β-d anomeric configuration were isolated, the chloride protected with non-participating groups (benzyl) afforded both anomers. The removal of the benzyl groups should be preceded by hydrolytic cleavage of the benzamido group. A simple procedure for fractionation, on small columns of silica gel, of reaction mixtures obtained in the fusion reactions is described.     

Synthesis of 2-(6-aminohexanamido)ethyl 1-thio-β-d-galactopyranoside and 1-thio-β-d-glucopyranoside,and related compounds

2-(6-Aminohexanamido)ethyl 1-thio-β-d-galactopyranoside (5) and 1-thio-β-d-glucopyranoside (9) were prepared by the following scheme: 2,3,4,6-tetra-O-acetyl-1-thio-β-d-aldopyranoses, generated from 2-S-(2,3,4,6-tetra-O-acetyl-β-d-aldopyranosyl)-2-thiopseudourea hydrobromides, were aminoethylated with ethylenimine, followed by N-acylation of the products with 6-(trifluoroacetamido)hexanoic acid (1), and O-deacylation. These reactions could be carried out consecutively without isolation of intermediates, and the products obtained after gel chromatography were de(trifluoroacetyl)ated to obtain the final products. The chain lengths of the aglycons were further extended by repeating the acylation and the de(trifluoroacetyl)ation. An analog containing glycerol in lieu of a sugar was prepared by a similar reaction-scheme.     

Reaction of Local Anesthetics with Phospholipids : A possible chemical basis for anesthesia

Local anesthetics (LA) have been found to interact with phospholipids and lipids extracted from nerve and muscle. This reaction is demonstrated by: (a) Inhibition by LA of phospholipid (and tissue lipid) facilitated transport of calcium from a methanol: water phase into chloroform. This action is dependent upon the cationic form of the LA. (b) LA increase the electrical resistance of "membranes" prepared by impregnating Millipore filters with cephalin:cholesterol or tissue lipid extracts and bathed with NaCl or KCl solutions. (c) LA coagulate aqueous dispersions of cephalin, phosphatidyl serine, phosphatidyl ethanolamine, and inositide, an action shared by calcium. The order of potency in coagulating cephalin sols is tetracaine > calcium > butacaine > procaine. Na⁺ and K⁺ do not coagulate phospholipid dispersions at 0.1 M concentration and antagonize the effect of Ca²⁺. (d) LA produce a marked fall in the pH of cephalin sols equivalent to that produced by calcium, (e) Ca²⁺ and LA form 1:2 molar complexes with phospholipids probably by ion-ion and ion-induced polar type of binding at the phosphate groups of the lipid. It is suggested that such reactions with cell membrane phospholipids may underlie inhibitory effects of LA on cellular ion fluxes and provide a chemical basis for anesthetic action.     

Plant-parasitic nematodes associated with olive tree (Olea europaea L.) with a focus on the Mediterranean Basin: A review

The olive tree (Olea europaea ssp. europaea.) is one of the most ancient cultivated trees. It is an emblematic species owing to its ecological, economic and cultural importance, especially in the Mediterranean Basin. Plant-parasitic nematodes are major damaging pests on olive trees, mainly in nurseries. They significantly contribute to economic losses in the top-ten olive-producing countries in the world. However, the damages they induce in orchards and nurseries are specifically documented only in a few countries. This review aims to update knowledge about the olive-nematode pathosystem by: (1) updating the list of plant-parasitic nematodes associated with olive trees; (2) analysing their diversity (taxonomic level, trophic groups, dominance of taxa), which allowed us (i) to assess the richness observed in each country, and (ii) to exhibit and describe the most important taxa able to induce damages on olive trees such as: Meloidogyne, Pratylenchus, Helicotylenchus, Xiphinema, Tylenchulus, Rotylenchulus, Heterodera (distribution especially in the Mediterranean Basin, pathogenicity and reactions of olive trees); (3) describing some management strategies focusing on alternative control methods; (4) suggesting new approaches for controlling plant-parasitic nematodes based on the management of the diversity of their communities, which are structured by several environmental factors such as olive diversity (due to domestication of wild olive in the past, and to breeding now), cropping systems (from traditional to high-density orchards), irrigation, and terroirs.     

Enzymatic oxidation of gallocatechin and epigallocatechin: effects of C-ring configuration on the reaction products

Tea leaf is rich in pyrogallol-type catechins, and their oxidation is important in the generation of black tea polyphenols. In the present study, the enzymatic oxidation of three pyrogallol-type catechins, (+)- and (−)-gallocatechins and (−)-epigallocatechin, was compared. The reactions yielded unstable quinone products, which were trapped as condensation products with o-phenylenediamine. The oxidation of (+)-gallocatechin proceeded very slowly compared to the reaction of (−)-epigallocatechin, and yielded a proepitheaflagallin-type dimer as the major product, though oxidation of (−)-epigallocatechin gave predominantly dehydrotheasinensin C. The cis-configuration of the C-3 hydroxyl group and the B-ring of (−)-epigallocatechin was apparently crucial for rapid and selective production of dehydrotheasinensin C. Oxidation of (−)-gallocatechin proceeded in a manner similar to that of (+)-gallocatechin, and produced an enantiomer of the (+)-gallocatechin product. The results suggest that enzymes catalyze oxidation of the pyrogallol B-ring to the o-quinone, with subsequent non-enzymatic coupling reactions proceed under highly steric control.     

A THEORY OF INJURY AND RECOVERY : II. EXPERIMENTS WITH MIXTURES.

1. The equations which serve to predict the injury of tissue in 0.52 M NaCl and in 0.278 M CaCl₂ and its subsequent recovery (when it is replaced in sea water) also enable us to predict the behavior of tissue in mixtures of these solutions, as well as its recovery in sea water after exposure to mixtures. 2. The reactions which are assumed in order to account for the behavior of the tissue proceed as if they were inhibited by a salt compound formed by the union of NaCl and CaCl₂ with some constituent of the protoplasm (certain of these reactions are accelerated by CaCl₂). 3. In this and preceding papers a quantitative theory is developed in order to explain: (a) the toxicity of NaCl and CaCl₂; (b) the antagonism between these substances; (c) the fact that recovery (in sea water) may be partial or complete, depending on the length of exposure to the toxic solution.     

ELECTROKINETIC PHENOMENA : VI. RELATIONSHIP BETWEEN ELECTRIC MOBILITY,CHARGE, AND TITRATION OF PROTEINS

1. By combining the theories of Smoluchowski, Debye and Hückel, and Henry it is possible to state explicitly (making necessary assumptions) under what conditions the following simple rule should be valid for proteins: In solutions of the same ionic strength, the electric mobilities of the same protein at different hydrogen ion activities should be proportional to the number of hydrogen (hydroxyl) ions bound. 2. Data of Tiselius and of the writer confirm this rule for (a) egg albumin, (b) serum albumin, (c) deaminized gelatin and gelatin, and (d) casein. 3. On the basis of the confirmed theory the titration curves of certain proteins are predicted from their mobilities. 4. It is shown that when certain proteins are adsorbed by quartz the apparent dissociation constant of the adsorbed protein is practically unchanged. The mass law must also be valid at the phase boundary. 5. The facts of paragraphs (1) to (4) are discussed in connection with the mechanism of (a) protein adsorption, (b) enzyme activity, (c) immune reactions, (d) the calculation of the electric charge of cells, and (e) criteria of surface similarity.     

Pathway of Uridine Diphosphate N-Acetyl-d-Glucosamine Biosynthesis in Phaseolus aureus

Studies with extracts obtained from mung beans (Phaseolus aureus) showed that UDP-N-acetyl d-glucosamine is formed from d-fructose 6-phosphate by a series of the following enzymic reactions: [Formula: see text]     

Platinum(II) triammine antitumour complexes: structure-activity relationship with guanosine 5′-monophosphate (5′-GMP)

The multinuclear (¹H, ¹⁵N, ³¹P and ¹⁹⁵Pt) NMR spectroscopies, ES-MS and HPLC have been employed to investigate the structure-activity relationship for the reactions between guanosine 5′-monophosphate (5′-GMP) and the platinum(II)-triamine complexes of the general formulation cis-[Pt(NH₃)₂(Am)Cl]NO₃ (where Am represents a substituted pyridine). The order of reaction rate of the reactions was found to be: 3-phpy > 4-phpy > py > 4-mepy > 3-mepy > 2-mepy. The two basic factors, steric and electronic, were attributed to the order of the binding rate constants. A possible mechanism of the reaction of cis-[Pt(NH₃)₂(Am)Cl]⁺ with 5′-GMP suggested that the reactions proceed via direct nucleophilic attack and no loss of ammonia. cis-[Pt(NH₃)₂(Am)Cl]⁺ binds to the N7 nitrogen of the guanine residue of 5′-GMP to form a coordinate bond with the Pt metal centre. This mechanism is apparently different from that of cisplatin. The pK_a value of cis-[Pt(NH₃)₂(4-mepy)(H₂O)](NO₃)₂ (5.63) has been determined at 298 K by the use of distortionless enhancement by polarization transfer (DEPT) ¹⁵N NMR spectroscopy and compared to the pK_a value of cis-[PtCl(H₂O)(NH₃)₂]⁺.     

ZnCl2 catalyzed new coumarinyl-chalcones as cytotoxic agents

A new series of coumarin-yl-chalcone derivatives (3a-m) had been designed and synthesized through different reactions such as aromatic addition, cyclization and Claisen-Schmidt reactions in good yields (54–78%). 5-acetyl-4-(2-hydroxyphenyl) -6-methyl-3, 4-dihydropyrimidin-2(1H) -one (1) has been synthesized by multi-component one pot reaction of salicylaldehyde, methyl acetoacetate and urea, which was further reacted with malonic acid employing ZnCl₂ catalyst to yield 5-acetyl-4-(4-hydroxy-2-oxo-2H-chromen-8-yl) -6-methyl-3, 4-dihydropyrimidin-2(1H) -one (2). The title compounds (3a-m) were synthesised by reacting 5-acetyl-4-(4-hydroxy-2-oxo-2H-chromen-8-yl) -6-methyl-3, 4-dihydropyrimidin-2(1H)-one (2) with different aromatic aldehydes in the presence of potassium hydroxide. In silico studies, a preliminary screening method for predicting the anti-cancer activity was performed for the synthesized compounds (3a-m) against Src, Alb tyrosine kinase and homology model protein (PDB ID: 4csv). The derivatives 3h and 3m showed moderate binding energies. The in vitro cytotoxic activity was evaluated for the compounds 3h and 3m by using human cancer cell-line morphology and MTT assay against three human cell-lines A549 (Lung), Jurkat (Leukemia) and MCF-7 (Breast). The results indicate that the derivatives 3h and 3m display significant anti-cancer activity, however it was found to be less cytotoxic when compared to the standard used i.e. Imatinib.     

Isomérisation des 5-bromo-5,6-dihydro-6-hydroxythymidines. Préparation des formes anomères de la thymidine et de la 1-(2-désoxy-D-érythro-pentofuranosyl)thymine

The trans 5-(R), 6-(R) and 5-(S), 6-(S) diastereoisomeric forms of 5-bromo-5,6-dihydro-6-hydroxythymidine were obtained by the action of bromine upon thymidine in aqueous solution. Treatment of these compounds with warm M hydrobromic acid both rearranges the sugar moiety and cleaves the glycosylamine bond; the yields of both processes were determined. Reduction of the halohydrins gave three isomeric compounds derived from thymidine : 1-(2-deoxy-α-D-erythro-pentofuranosyl)thymine, 1-(2-deoxy-β-D-erythro-pentopyranosyl)thymine and 1-(2-deoxy-α-D-erythro-pentopyranosyl)thymine. These isomerisations were also shown in the treatment of thymidine with hydrobromic acid, but, in the latter case, the process is less productive than in the former one. A mechanism for these reactions is discussed.