2,2′-Bipyridine-Modified Tamoxifen: A Versatile Vector for Molybdacarboranes

Investigations on the antitumor activity of metallacarboranes are sparse in the literature and limited to a handful of ruthena- and molybdacarboranes. In this study, the molybdacarborane fragment [3-(CO)₂-closo-3,1,2-MoC₂B₉H₁₁] was combined with a vector molecule, inspired by the well-known drug tamoxifen or 4,4′-dihydroxytamoxifen (TAM-diOH). The molybdacarborane derivative [3,3-{4-[1,1-bis(4-hydroxyphenyl)but-1-en-2-yl]-2,2′-bipyridine-κ²N,N′}-3-(CO)₂-closo-3,1,2-MoC₂B₉H₁₁] ( 10 ), as well as the ligand itself 4-[1,1-bis(4-hydroxyphenyl)but-1-en-2-yl]-2,2′-bipyridine ( 6 ) showed cytotoxic activities in the low micromolar range against breast adenocarcinoma (MDA-MB-231, MDA-MB-361 and MCF-7), human glioblastoma (LN-229) and human glioma (U-251) cell lines. In addition, compounds 6 and 10 were found to induce senescence and cytodestructive autophagy, lower ROS/RNS levels, but only the molybdacarborane 10 induced a strong increase of nitric oxide (NO) concentration in the MCF-7 cells.     

Evaluation of Benzo[c]Chrysene Dihydrodiols in the Morphological Cell Transformation of Mouse Embryo Fibroblast C3H10T1/2CL8 Cells

The morphological cell transforming activities of three dihydrodiols of benzo[c]chrysene (B[c]C), trans?B[c]C-7,8-diol, trans?B[c]C-9,10-diol, and trans?B[c]C-1,2-diol were compared to those of B[c]C in order to study the possible routes of metabolic activation in transformable C3H10T1/2 mouse embryo fibroblasts. B[c]C-treated C3H10T1/2 cells exhibited a concentration-related increase in morphologically transformed foci over a concentration range of 0–3 μg/ml. At 3 μg/ml, B[c]C induced 1.23 Type II & III foci/dish, with 73% of the dishes exhibiting Type II or Type III foci, and a survival of 87%. trans?B[c]C-7,8-diol produced concentration-related responses over a range of 0–5 μg/ml. At 3 μg/ml, trans?B[c]C-7,8-diol produced 1.13 Type II & III foci/dish with 72% of the dishes exhibiting foci, and a survival of 76%. trans?B[c]C-9,10-diol was inactive as a morphological cell transforming agent over a concentration range of 0–3 μg/ml. trans?B[c]C-1,2-diol was also inactive as a morphological cell transforming agent over a concentration range of 0–3 μg/ml. These results suggest that a K-region dihydrodiol of B[c]C, trans?B[cC-7,8-diol, may play a role in the ability of B[c]C to morphologically transform C3H10T1/2 cells.     

Über die Pyrolyse von Pent-1-en-4,4,5,5,5-d5

On the Pyrolysis of Pent-1-ene-4,4,5,5,5-d₅ The distribution of deuterium in the main products of thermal decomposition of pent-1-ene-4,4,5,5,5-d₅ at 550 to 650°C was studied and interpreted. The results include conclusions on kinetic isotope effects, on relative reactivities of different C- H -bonds, on the proportion of terminal and nonterminal addition of methyl radicals, and on the importance of a radical isomerisation reaction. It was shown that the molecular decomposition (Retro-En-Reaction) cannot successfully compete with the radical way in the temperature range above 600°C     

Verwendung neuer halogenpolyole zur PUR-hartschaumerzeugung mit verminderter brennbarkeit

The usefulness of 3,5-dibromohexane-1,4-diol, 3,5-dichloroheptane-1,4-diol, 3,5-dibromoheptane-1,4-diol, 2-(4,5-dichlorophentyl)propane-1,3-diol and 2-(4,5-dibromopentyl)propane-1,3-diol for the synthesis of rigid polyurethane foams with reduced combustibility was investigated. In addition possibility of utilization of hexane-1,4-diol, heptane-1,4-diol, 2-(pent-4-enyl)propane-1,3-diol and 6-hydroxymethylheptane-1,2,7-triol for the manufacture of foamed polyurethanes is examined too.     

巴斯德梭菌甘油脱水酶基因的克隆表达、纯化及酶学性质的研究

用聚合酶链反应(PCR)技术,从巴斯德梭菌(C lostridium pasteurianum)扩增出甘油脱水酶基因(dhaBCE),在大肠杆菌中高效表达,SDS-PAGE(聚丙烯酰胺凝胶)电泳结果显示,分别有相对分子质量为66、21、16 kD三条特异性蛋白表达条带。用金属镍亲和层析及S-300H凝胶层析将重组蛋白进行分离纯化,所得纯酶的比活为4.26 U/mg。重组酶的最适反应温度42~44℃,最适作用pH=9.10~9.50,它对三个底物结构类似物的米氏常数(Km)值分别是:1,2-丙二醇0.38 mmol/L,甘油0.29 mmol/L,1,2-乙二醇2.0 mmol/L;对辅酶B12的Km值为0.22μmol/L。     

Hydrogels based on hydrophilic side-chain siloxanes

Methacrylate end-capped diethylene glycol propyl methyl ether, 5-hexyl-1,2-diol, and 3-propyloxy-1,2-propane diol side-chain siloxanes were evaluated for potential use as hydrogels for contact lens application. The preparation of the methacrylate end-capped ether, hexane diol, and propane diol side-chain siloxanes was accomplished in two relatively simple synthetic steps: The first step consisted of the acid-catalyzed co-ring opening polymerization of octamethylcyclotetrasiloxane, tetramethylcyclotetrasiloxane, and 1-3-bis-methacryloyl-butyltetramethyldisiloxane, followed by a platinum-catalyzed hydrosilation with (in separate experiments) diethylene glycol allyl methyl ether, trimethylsilyl protected 3-allyloxy-1,2-propane diol, and trimethylsilyl protected 5-hexene-1,2-diol. The trimethylsilyl protecting groups was removed using a 10% 0.1N HCl solution in 2-propanol. Radical polymerization of the methacrylate end-capped ether, hexane, and propane diol side-chain siloxanes with hydrophilic monomers, such as dimethylacrylamide, and a strengthening agent, isobornylmethacrylate, resulted in transparent hydrogels possessing a wide range of water contents, high oxygen permeability, and a low modulus of elasticity and, for the propane diol side-chain siloxanes, excellent hydrolytic stability. The ether side-chain siloxane-based hydrogels exhibited poor hydrolytic stability. © 1995 John Wiley & Sons, Inc.     

Characterization of Terpenoids from the Root of Ceriops tagal with Antifouling Activity

One new dimeric diterpenoid, 8(14)-enyl-pimar-2'(3')-en-4'(18')-en-15'(16')-endolabr- 16,15,2',3'-oxoan-16-one (1) and five known terpenoids: Tagalsin C (2), Tagalsin I (3), lup-20(29)-ene-3β,28-diol (4), 3-oxolup-20(29)-en-28-oic acid (5) and 28-hydroxylup- 20(29)-en-3-one (6) were isolated from the roots of the mangrove plant Ceriops tagal. Their structures and relative stereochemistry were elucidated by means of extensive NMR, IR and MS analysis. The antifouling activity against larval settlement of the barnacle Balanus albicostatus were evaluated using capsaicin as a positive control. All these terpenoids exhibited antifouling activity against cyprid larvae of the barnacle without significant toxicity. The structure-activity relationship results demonstrated that the order of antifouling activity was diterpenoid (Compound 2) > triterpenoid (Compounds 4, 5 and 6) > dimeric diterpenoid (Compounds 1 and 3). The functional groups on the C-28 position of lupane triterpenoid significantly affect the antifouling activity. The diterpenoid dimmer with two identical diterpenoid subunits might display more potent antifouling activity than one with two different diterpenoid subunits. The stability test showed that Compounds 2, 4, 5 and 6 remained stable over 2-month exposure under filtered seawater.     

Kinetischer H/D-Isotopeneffekt der Photooxidation von 3,5-Dimethyl-1,1-dioxo-2-(p-tolyl)-1,2-thiazin durch Singulettsauerstoff

Kinetic H/D Isotope Effect of the Photooxidation of 3,5-Dimethyl-1,1-dioxo-2-(p-tolyl)-1,2-thiazine by Singlet Oxygen The hydrogen atoms of the thiazine ring and of the methyl groups of 3,5-dimethyl-1,1-dioxo-2-(p-tolyl)-1,2-thiazine 1a can be exchanged by deuterium in basic or acidic deutero methanol (CH₃OD). In CD₃OD/D₂SO₄ the rate of the H/D-exchange of the different protons of 1a was determined by ¹H-n.m.r. spectroscopy. A kinetic isotope effect of 1.5–1.8 was determined from the rate of the oxygen consumption and also by using a competitive method. The results are in accordance with an “ene” reaction of 1a with singlet oxygen.     

Acetals and Ethers. XVIII. Reaction products of prop-2-enal and but-2-enal with mixture: n-Aliphatic alcohol and ethylene glycol

The direct condensation reaction of prop-2-enal or but-2-enal with mixture of n-aliphatic alcohol and ethylene glycol, in the presence of p-toluenesulphonic acid as catalyst, leads to a complex mixture of saturated, unsaturated, cyclic and linear acetals, moreover, 2-(2-alkoxy-alkyl)-1,3-dioxolanes are the main reaction products. The detailed investigations for n-butanol showed that unsaturated cyclic acetals: 2-vinyl-1,2-dioxolane 1a or 2-(1-propenyl)-1,3-dioxolane 1b , as well as unsaturated linear acetals: 1,1-dibutoxy-prop-2-en 2a or 1,1-dibutoxy-but-2-en 2b are intermediate reaction products. Additionally, it was found in final products presence of eight by-products: 5-butoxy- 4a or 5-butoxy-7-methyl-1,4-dioxepane 4b , 1,1,3-tributoxypropane 5a or 1,1,3-tributoxybutane 5b , 2-[2-(2-hydroxyethoxy)ethyl]- 6a or 2-[2-(2-hydroxyethoxy)propyl]-1,3-dioxolane 6b , 5-(2-hydroxyethoxy)-7-methyl-1,4-dioxepane 7b , 1,3-dibutoxy-1-(2-hydroxyethoxy)-propane 8a or 1,3-dibutoxy-1-(2-hydroxyethoxy)-butane 8b , 1,1-dibutoxy-3-(2-hydroxyethoxy)-propane 9a or 1,1-dibutoxy-3-(2-hydroxyethoxy)-butane 9b , 3-butoxy-1,1-bis-(2-hydroxyethoxy)-propane 10a or 3-butoxy-1,1-bis-(2-hydroxyethoxy)-butane 10b , and 1-butoxy-1,3-bis-(2-hydroxyethoxy)-propane 11a or 1-butoxy-1,3-bis-(2-hydroxyethoxy)-butane 11b , respectively.     

Studies on hexolic anhydride based polyesters,II. Thermogravimetric analysis

Unsaturated polyesters based on hexolic anhydride (5,6,7,8,9,9-hexachloro-1,2,3,4,4a,5,8,8a-octahydro-5,8-methanonaphthalene-2,3-dicarboxylic anhydride), maleic anhydride, phthalic anhydride, cis-2-butene-1,4-diol, 2,3-dichloro-2-butene-1,4-diol and 2,3-dibromo-2-butene-1,4-diol were synthesized. The thermal behaviour of the polyesters was studied using thermogravimetric technique. The results were compared with those available for other hexolic anhydride and HET-acid (1,4,5,6,7,7-hexachlorobicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic acid) based polyesters. The direct study and comparative study of the polyesters revealed that the bromodiol is prominent in increasing the flame retardant character of the polyesters in which it is incorporated; alkenic diols are inferior compared to saturated diols regarding the thermal stability of the polyesters; as the number of carbon atoms in the saturated diol increases, the stability and flame retardancy of the polyesters decrease; branching in the diol part decreases the stability of the polyesters, with hexolic anhydride based polyesters being thermally more stable than HET-acid based polyesters.     

新型凉味剂L-薄荷氧基丙二醇的合成研究

以L -薄荷醇和 1,2 -环氧 - 3-氯丙烷等为原料 ,经取代、环氧化、水解等一系列反应合成新型凉味剂L -薄荷氧基丙二醇     

Revisiting the Mechanism of β-O-4 Bond Cleavage During Acidolysis of Lignin. Part 3: Search for the Rate-Determining Step of a Non-Phenolic C6-C3 Type Model Compound

Abstract

The rate-determining step of a C₆-C₃ dimeric non-phenolic β-O-4 type lignin model compound, 2-(2-methoxyphenoxy)-1-(3,4-dimethoxyphenyl)propane-1,3-diol (veratrylglycerol-β-guaiacyl ether, VG), was evaluated under acidolysis conditions (0.2 mol/l HBr in 82% aqueous 1,4-dioxane at 85°C) by comparing the disappearances between VG and the corresponding compound labeled at the β-position of VG, 2-(2-methoxyphenoxy)-1-(3,4-dimethoxyphenyl)(2–²H)propane-1,3-diol. The disappearance of VG occurred more rapidly than that of the latter compound, and a primary kinetic isotope effect was clearly observed. This result indicates that the C-H bond at the β-position of VG is broken in the rate-determining step. Two possible mechanisms are presented as the rate-determining step: (1) A base abstracts the β-proton of a benzyl cation-type intermediate produced from VG affording an enol ether compound, 2-(2-methoxyphenoxy)-3-(3,4-dimethoxyphenyl)prop-2-en-1-ol; (2) The hydride transfers from the β- to the α-position of the benzyl cation. It was confirmed that both mechanisms certainly exist and that the latter seems to contribute more than has generally been considered.     

Synthesis of Ester Based Cationic Pyridinium Gemini Surfactants and Appraisal of Their Surface Active Properties

New pyridinium gemini surfactants have been synthesized by esterification of halogenated carboxylic acids with long chain fatty alcohols furnishing respective esters (dodecyl-2-chloroacetate, tetradecyl-2-chloroacetate, hexadecyl-2-chloroacetate, dodecyl-2-bromoacetate, tetradecyl-2-bromoacetate and hexadecyl-2-bromoacetate) followed by their subsequent treatment with 4,4′-trimethylene dipyridine resulting in the formation of title Gemini surfactants: 4,4′-(propane-1,3-diyl)bis1-{2-(dodecyloxy)-2-oxoethyl}; 4,4′-(propane-1,3-diyl)bis{1-(2-(tetradecyloxy)-2-oxoethyl}; 4,4′-(propane-1,3-diyl)bis{1-(2-(hexadecyloxy)-2-oxoethyl} dipyridinium chlorides; 4,4′-(propane-1,3-diyl)bis{1-(2-(dodecyloxy)-2-oxoethyl}; 4,4′-(propane-1,3-diyl)bis{1-(2-(tetradecyloxy)-2-oxoethyl} and 4,4′-(propane-1,3-diyl)bis{1-(2-(hexadecyloxy)-2-oxoethyl} dipyridinium bromides. Their identifications are based on IR, ¹H-NMR, ¹³C-NMR, DEPT, COSY and Mass spectral studies. Their surface active properties were also evaluated on the basis of surface tension and conductivity measurements.     

Halogenlipide. III. Alkyl-glyceryl-ether-Analoga

Halogenolipids. III. Alkyl Glyceryl Ether Analogues Synthesis of the halogeno analogues of alkyl glycerol ether, 3-fluoro-1-O-hexadecyl-(octadecyl)-propane-1, 2-diol, 2-fluoro-1-O-hexadecyl(octadecyl)-propane-1, 3-diol, 2-chloro-1-O-hexadecyl-propane-1,3-diol and 3-fluoro-2-O-hexadecyl-propane-1,2-diol, which are of interest as potential cytostatic agents, is described.     

Development of an (S)-1-{2-[tris(4-methoxyphenyl)methoxy]ethyl}piperidine-3-carboxylic acid [(S)-SNAP-5114] carba analogue inhibitor for murine γ-aminobutyric acid transporter type 4

A series of GABA uptake inhibitors related to (S)-1-{2-[tris(4-methoxyphenyl)methoxy]ethyl}piperidine-3-carboxylic acid [(S)-SNAP-5114], the most potent mGAT4 inhibitor known so far, were synthesized and biologically evaluated for their inhibitory potency at the four GABA uptake transporters mGAT1-4 stably expressed in HEK-293 cell lines. New analogues were developed with potencies that are similar to or slightly higher than those of current mGAT4 inhibitors, but with distinctly improved chemical stability. (S)-Nipecotic acid derivatives possessing a 2-[1-(4-methoxy-2-methylphenyl)-1,1-bis(4-methoxyphenyl)methoxy]ethyl (DDPM-859) or a 4,4,4-tris(4-methoxyphenyl)but-2-en-1-yl moiety (DDPM-1457) were found to exhibit pIC(50) values of 5.78 and 5.87, respectively. Thus, as mGAT4 inhibitors, these compounds compare well with (S)-SNAP-5114 (pIC(50) =5.71), but are far more stable than the latter. Moreover, DDPM-859 displays a more favorable subtype selectivity for mGAT4 versus mGAT3 than does (S)-SNAP-5114.     

Functionalization of poly(ε-caprolactone) by pendant hydroxyl, carboxylic acid and epoxide groups by atom transfer radical addition

A straightforward strategy is proposed for grafting hydroxyl, carboxylic acid and epoxide groups along poly(ε-caprolactone) chains. Statistical copolymerization of ε-caprolactone (εCL) with α-chloro-ε-caprolactone (αClεCL) has been initiated by 2,2-dibutyl-2-stanna-1,3-dioxepane (DSDOP), followed by the atom transfer radical addition (ATRA) of but-3-en-1-ol, vinylacetic acid and 1,2-epoxyhex-5-ene, respectively, onto the α-chloro units of a poly(αClεCL-co-εCL) copolymer. αClεCL is easily prepared by the Baeyer-Villiger oxidation of 2-chlorocyclohexanone. The influence of the experimental conditions, i.e. temperature, solvent, catalyst, on the grafting yield has been discussed. Because ATRA is tolerant of the investigated functional groups, no protection/deprotection reaction is required, which is a major advantage of the method.     

Synthesis of substituted fatty oxathiolanes and thioethers from an allylic oxo fatty acid ester

Substituted oxathiolane and thioether derivatives have been synthesized from an allylic oxo fatty acid ester. The reaction of methyl 4-oxo-trans-2-octadecenoate with 3-mercaptopropan-1,2-diol (1-thioglycerol) affords methyl 4-(3′-hydroxymethyl-1′,4′-oxathiolane)-2(3)-(O-mercaptopropan-1″,2″-diol)-octadecanoate (II), methyl 4-oxo-2(3)-(O-mercaptopropan-1′,2′-diol)-octadecanoate (III), methyl 4-(3′-hydroxy-l′,5′-oxathiane)-2 (3)-(S-mercaptopropan-1″,2″-diol)-octadecanoate (IV), methyl 4-oxo-2(3)-(S-mercaptopropan-1′, 2′diol)-octadecanoate (V) and methyl 4-(3′-hydroxymethyl-1′, 4′-oxathiolane)-2(3)-(S-mercaptopropan-1″, 2″-diol)-octadecanoate (VI). Structures of the individual reaction products have been established on the basis of spectral data and microanalyses.     

HPLC method for quantitation of cholesterol and four of its major oxidation products in muscle and liver tissues

A fast, sensitive, high performance liquid chromatographic method was developed for the quantitation of cholesterol and four of its major oxidation products: 3β-hydroxycholest-5-en-7-one (7-ketocholesterol), cholest-5-ene-3β, 7α-diol (7α-hydroxycholesterol), cholest-5-ene-3β,7β-diol (7β-hydroxycholesterol), and cholest-5-ene-3β,25-diol (25-hydroxycholesterol). In this procedure 2∶1 chloroform:methanol (v/v) extracts of tissue homogenate were combined, dried over anhydrous Na₂SO₄, filtered, evaporated to dryness under N₂ and dissolved with a mobile phase of either 97∶3 or 93∶7 hexane:isopropanol (v/v). After membrane filtration and without further purification, aliquots were directly injected onto a 10-μm pore size, 30×0.39 cm μ-Porasil normal phase column. The separation of cholesterol and its oxidation products was monitored by a UV detector at 206 and 233 nm. This method was successfully applied to pork muscle as well as mouse liver tissues and was able to detect cholesterol oxidation products (COP) in the ppm range. The identity of the COP was confirmed by mass spectroscopy.     

Synthesis of trideuteratedO-alkyl platelet activating factor and lyso derivatives

Racemic heavy isotope analogs of 1-O-alkyl-sn-glycero-3-phosphocholine (lysoPAF) and 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine (PAF) were prepared for use as internal standards to facilitate quantitative studies based on mass spectrometry. Starting from pentadencane-1,15-diol andrac-glycerol-1,2-acetonide, a convergent synthesis of 1-O-[16′-²H₃]hexadecyl and 1-O-[18′-²H₃]octadecylrac-glycero-3-phosphocholine and their acetyl derivatives is described. Three deuterium atoms were introduced at the terminal position of the 1-O-alkyl group by displacement of thep-toluensulfonyl group from 1-O-alkyl-15′-p-toluensulfonate and 1-O-alkyl-17′-p-toluensulfonate with [²H₃]-methylmagnesium iodide. The 1-O-alkyl-17′-p-toluensulfonate was obtained by reaction of the 1-O-alkyl-15′-p-toluensulfonate with allylmagnesium bromide, followed by reductive ozonolysis and treatment withp-toluenesulfonyl chloride. The hydroxyl group at C-2 was protected by a benzyl group and removed at a late stage in the synthesis. This provided the corresponding lysoderivatives or allowed preparation of racemic PAF by subsequent acetylation of the free hydroxy group. The phosphocholine moiety was introduced at glycerol C-3 by reaction with bromoethyldichlorophosphate and trimethylamine. The synthetic compounds were analyzed by FAB/MS and GC/NICIMS. They were shown to contain less than 0.6% protium impurity.     

Evidence for the combined participation of a C10 and a C15 precursor in the biosynthesis of moenocinol, the lipid part of the moenomycin antibiotics

Upon feeding of [2-(13)C,4-(2)H]-1-deoxy-D-xylulose to Streptomyces ghanaensis, the deuterium label was retained exclusively at positions C-7 and C-17 in the moenocinol part of the moenomycin antibiotics. This result vindicates the hypothesis that the C(25) structure of moenocinol is assembled from a C(10) and a C(15) precursor, each of which requires for its formation the involvement of a dimethylallyl diphosphate starter unit.