Inhibitory effect of 2-(E-2-alkenoylamino)ethyl alkyl sulfides on gastric ulceration in rats. II. Structure and activity relationships of 2-(E-n or Z-n-Decenoylamino)ethyl alkyl sulfides

The analogues of 2-(E-n or Z-n-decenoylamino)ethyl carbamoylmethyl sulfide, including the modifications of sulfide portion, double bond in decenoyl chain and alkyl sulfide moiety, were synthesized and their inhibitory effects on stress-induced ulceration in rats were compared. Replacing the sulfura atom by methylene group or oxygen atom reduced the effect of potency. Saturation of the double bond in the decenoyl chain tended to reduce the anti-ulcerogenic activity in rats. There was no relationship between the position of double bond in decenoyl chain and the pharmacological activity. On the other hand, compounds with E-configuration showed stronger anti-ulcer activity than the corresponding Z-type of compounds. Among 9 kinds of S substituted alkyl groups for carbamoylmethyl, 2-(E-2-decenoylamino)ethyl 2-cyclohexylethyl sulfide showed the most potent anti-ulcerogenic activity in rats and also showed the lowest acute toxicity in mice.     

Parameterising matrix-assisted laser desorption/ionisation (MALDI): strategy for matrix—analyte selection and effect of radical co-additives on analyte peak intensities

Dihydroxybenzoic acid (DHB) analogues substituted at the 5-position can act as UV matrices at a wavelength of 337 nm, even when their absorption maxima are shifted past this particular wavelength.Modification of a matrix with a chiral ligand γ-(3-carboxy-4-hydroxy-anilide) (GCA) allowed it to differentiate between chiral isomers of tryptophan and also gave different intensities for glucose isomers, including structural dimers of glucose (cellobiose and maltose).An analogue that had one free hydroxyl group at the 2-OH position and a modification at the 5-position (MY10) gave protonated substance P (SP, analyte) peaks, similar in intensity to the not derivatised parent 2,5-dihydroxybenzoic acid indicating that the 5-OH position is not an important structural component.Another analogue that resembled a ‘dendrimeric’ structure of DHB (M552), also acted as a matrix, although its absorption maxima was at 552 nm suggesting the possibility of it being used at other wavelengths in addition to 337 nm.The DHB radical was complexed to a nitrone ‘spin-trap’. On complexion, the peptide (SP) peak intensity decreased. Addition of either radical initiators, such as 2,2-azobis(iso-butyronitrile) AIBN and tert-butylperoxide, or other radicals such as 2,2,6,6-tetramethyl-1-piperidinyloxy free radical (TEMPO) gave rise to higher analyte peak intensities for [SP+Na]⁺.It is thought that the DHB neutral radical is an intermediary in the protonation of the analyte. The photo-fragments of DHB, specifically the m/z 137 species, may also take part in proton transfer since possible mass analogues (hydroquinone, (deoxy)benzoin) can lead to analyte enhancement. Stabilization of or an increase in the matrix radical can also lead to analyte signal enhancement.     

Parameterising matrix-assisted laser desorption/ionization (MALDI): effect of solvents and co-additives on analyte peak intensities

The peak intensities obtained when 2,5-dihydroxybenzoic acid (DHB) was used as a 'classic' matrix were measured using substance P (SP) and betacyclodextrin (BCD) as analytes. Enhancements in peak intensities were observed going from 1:1 MeOH/H2O to dimethylforamide (DMF) as matrix solvents. Also non-covalent interactions between SP and solvent and DHB were observed suggesting close interactions between matrix, solvent and analyte in the gas-phase. Peak enhancements were previously reported with 'superDHB' (DHB and 2-hydroxy-5-methoxybenzoic acid at 10% v/v). Co-addition of structural analogues and their respective absorption coefficients were determined. It was found that other analogues used as co-matrices could give analyte peak enhancement similar to reported for sDHB with the additional benefit that some analogues could act as matrices with DHB addition. No direct correlation was observed between absorption coefficient and the ability of the molecule to act as a 'good' UV MALDI matrix.     

Synthesis and evaluation of structural requirements for antifungal activity of cyrmenin B1 analogues

In a study aiming to define the structural elements essential to cyrmenin B₁ antifungal activity, the synthesis of a series of analogues was carried out. The structural modification introduced stepwise in distinct areas of the parent molecule allowed a deeper insight to be gained into the most relevant structural features affecting the activity of the natural compound. The bioassay results clearly indicate the relevance of each portion of the parent molecule, only the modification of the conjugated double bond geometry being tolerated.     

Electrophilic cleavage of cyclopropylmethystannanes: an experimental comparison of sigma-sigma and sigma-pi conjugation

[reaction: see text] Cyclopropylmethyltrimethylstannanes undergo electrophilic cyclopropane cleavage in chloroform with simple inorganic electrophiles (H(+), SO(2), I(2)) in a homologous reaction to the S(E)' cleavage of allylic stannanes. The sigma-sigma conjugation between the carbon-tin bond and cyclopropane orbitals observed spectroscopically in the parent cyclopropylmethyltrimethylstannane is responsible for a rate enhancement of ca. 10(2) toward iodinolysis, relative to comparable alkyl stannanes. This acceleration is considerably less, however, than the ca. 10(9)-fold rate enhancement provided by the corresponding sigma-pi conjugation in allylic stannanes. Methanol-tin coordination appears to reduce the activating influence of the metal, promoting methyl cleavage over cyclopropane fission with acid and iodine. Decreased sigma-sigma conjugation can also explain the decreased reactivity of cyclopropyltriphenylstannane compared with its trimethyltin counterpart. Cyclopropylmethylstannanes do not undergo the synthetically useful addition of aldehydes under conditions that facilitate the corresponding reaction of allylic stannanes.     

吐温表面活性剂囊泡对姜黄素的包载作用

本文研究了烷基链不饱和度对吐温表面活性剂囊泡包载姜黄素的影响。相比吐温-80囊泡,吐温-60囊泡的包载使姜黄素表现出更大的紫外吸收和荧光发射强度、缔合常数和DPPH自由基清除能力。核磁共振氢谱结果表明姜黄素缔合于吐温-60囊泡双分子层中的亲水头基附近,而且姜黄素的酚羟基与吐温-60的酯基产生氢键作用。在吐温-80囊泡中,双键会使吐温-80烷基链产生弯曲或折叠,导致双分子层排列更加松散、极性更高。因此,姜黄素除了与吐温-80的酯基产生氢键作用外,还能与吐温-80烷基链尾部和中部的亚甲基发生作用。     

Wheat digalactosyldiacylglycerol molecular species profiling using porous graphitic carbon stationary phase

The potential of porous graphitic carbon stationary phase (PGC) was assessed for the separation of molecular species of digalactosyldiacylglycerol (DGDG). Detection was by an evaporative light scattering detector (ELSD). A conventional optimization strategy allowed definition of a quaternary non-aqueous mobile phase and separation of 9 wheat DGDG molecular species with isocratic elution: methanol/toluene/tetrahydrofuran/chloroform 64.3/21.5/13.7/0.5 v/v with 0.1% of triethylamine and a stoichiometric amount of formic acid. The molecular species were identified by LC/MS. The chromatographic behavior of DGDG on PGC was then compared to previous studies. The addition of a carbon double bond on the alkyl chain decreased the retention. This contribution was less important when the number of unsaturations increased in the alkyl chain. The consequence of this retention behavior with PGC was an elution order of molecular species which did not agree with the partition number as observed with C18 grafted stationary phases.     

Synthesis of benzophenone-containing analogues of phosphatidylcholine

As part of a collaborative study of cellular efflux of cholesterol and phospholipids, photoactivable analogues 4-8 of phosphatidylcholine (PC) having benzophenone groups in the choline moiety and at the end of the C2 and C1 alkyl chains have been synthesized. The efficient preparation via Suzuki coupling of the appropriate long-chain benzophenone-containing carboxylic acid and alcohol and their incorporation by adaptation of known approaches into the acyl- and ether-linked PC analogues 6-8 are described. Development of a method for radiolabeling these PC analogues, via hydrogenation of a double bond in modified side chains, is also described.     

The Formation of Terminal Double Bonds in Vinyl Chloride Polymerization

The determination of double bonds in PVC is achieved with an increased accuracy in comparison with earlier methods by the addition of iodine monochloride (Wijs reaction) to PVC coupled with x-ray fluorescence analysis to determine the iodine content of the polymer. The number of double bonds per unit weight of polymer increases on increasing the polymerization temperature and is proportional to the number of polymer molecules. It is not affected, however, by the presence of the chain transfer agent tetrahydrofuran (THF). At the technically important polymerization temperatures of 30 to 80°C and in the absence of the chain transfer agent, 0.9 double bonds per polymer molecule are found. The number of double bonds per polymer molecule is lowered using the chain transfer agent THF. These results support the theory that the chain transfer to monomer and possibly the termination reaction are coupled with the formation of terminal double bonds. Contributions by internal double bonds formed by dehydrochlorination of the polymer during polymerization are excluded by investigating the Cl^θ content of the water phase in the oxygen-free VC suspension polymerization. No hydrogen chloride is formed. In IR spectra of PVC, the stretching vibration of the double bonds is detected at 1667 cm^?1 by the correlation of the double bond contents and the intensities of the absorption bands. The stretching vibration at 1667 cm^?1is in accordance with those of model compounds with a 1-chloro-2-alkene structure.     

A Total Synthesis of Spirastrellolide A Methyl Ester

A concise total synthesis of spirastrellolide A methyl ester ( 1 a , R¹=Me) as the parent compound of a series of highly cytotoxic marine macrolides is disclosed, which exploits and expands the flexibility of a synthesis plan previously developed by our group en route to the sister compound spirastrellolide F methyl ester ( 6 a , R¹=Me). Key to success was the masking of the signature Δ^15,16‐bond of 1 a as a C16‐carbonyl group until after the stereogenic center at C24 had been properly set by a highly selective hydrogenation of the C24 exo‐methylene precursor 66 . Conformational control over the macrocyclic frame allowed the proper stereochemical course to be dialed into this reduction process. The elaboration of the C16 ketone to the C15–C16 double bond was accomplished by a chemoselective alkenyl triflate formation followed by a palladium‐catalyzed hydride delivery. The role of the ketone at C16 as a strategic design element is also evident up‐stream of the key intermediate 66 , the assembly of which hinged upon the addition of the polyfunctionalized dithiane 37 to the similarly elaborate aldehyde fragment 46 . Other crucial steps of the total synthesis were an alkyl‐Suzuki coupling and a Yamaguchi lactonization that allowed the Northern and the Southern sector of the target to be stitched together and the macrocyclic perimeter to be forged. The lateral chain comprising the remote C46 stereocenter was finally attached to the core region by a modified Julia–Kocienski olefination. The preparation of the individual building blocks led to some methodological spin‐offs, amongst which the improved procedure for the N–O‐bond cleavage of isoxazolines by zero‐valent molybdenum and the ozonolysis of a double bond in the presence of other oxidation‐prone functionality are most noteworthy. Preliminary biological data suggest that the entire carbon framework, that is the macrocyclic core plus the lateral chain, might be necessary for high cytotoxicity.     

The synthesis and liquid crystal transition temperatures of some weakly polar nematic trans-4-substituted-cyclohexyl (E)-alk-2-enoates

The effect on the liquid crystal transition temperatures of introducing various groups (for example incorporating C=C, O, CO₂ and CO) into the terminal alkyl chain of a weakly polar model compound 1-[trans-4-(trans-4-propylcyclohexyl)cyclohexyl]pentane has been investigated systematically. Only the compound containing both an ester function and a trans-carbon-carbon double bond exhibited a wide-range nematic mesophase at elevated temperatures. Therefore, a wide variety of trans-4-substituted-cyclohexyl (E)-alk-2-enoates incorporating a carbon double bond with a trans-configuration (E) in the terminal alkyl chain has been synthesized. Nearly all the two-ring esters prepared exhibit a nematic phase over a wide temperature range (≤ 100°C) at elevated temperatures (≤ 200°C). The tendency to form smectic mesophases is often low. Comparisons with the corresponding derivatives incorporating either just a carboxy group (COO) or just a carbon-carbon double bond (C=C) in the same positions indicate that synergetic effects lead to broader nematic phases than would otherwise have been expected. The new compounds are easily prepared from known starting materials.     

Efficient method to locate double bond positions in conjugated trienes

The double bond positions of 11 conjugated trienes were unambiguously located through a simple derivatization method amenable to nanogram-scale analyses. The trienes were reacted with the powerful dienophile 4-methyl-1,2,4-triazoline-3,5-dione (MTAD), and the mass spectra of the resulting cycloadducts exhibited large diagnostic fragments which allowed the unequivocal location of the double bonds in the parent triene in most cases. Catalytic hydrogenation of the cycloadducts produced saturated compounds with characteristic mass spectral fragments from which the positions of the trienes in the parent compounds could be readily confirmed. Application of the method was demonstrated by the microscale identification of two conjugated triene and one conjugated diene components from extracts of the sex pheromone gland of the saturniid moth Automeris cecrops pamina.     

(9Z)- and (11Z)-8-methylretinals for artificial visual pigment studies: stereoselective synthesis, structure, and binding models

Artificial visual pigment formation was studied by using 8-methyl-substituted retinals in an effort to understand the effect that alkyl substitution of the chromophore side chain has on the visual cycle. The stereoselective synthesis of the 9-cis and 11-cis isomers of 8-methylretinal, as well as the 5-demethylated analogues is also described. The key bond formations consist of a thallium-accelerated Suzuki cross-coupling reaction between cyclohexenylboronic acids and dienyliodides (C6-C7), and a highly stereocontrolled Horner-Wadsworth-Emmons or Wittig condensation (C11-C12). The cyclohexenylboronic acid was prepared by trapping the precursor cyclohexenyllithium species with B(OiPr)(3) or B(OMe)(3). The cyclohexenyllithium species is itself obtained by nBuLi-induced elimination of a trisylhydrazone (Shapiro reaction), or depending upon the steric hindrance of the ring, by iodine-metal exchange. In binding experiments with the apoprotein opsin, only 9-cis-5-demethyl-8-methylretinal yielded an artificial pigment; 9-cis-8-methylretinal simply provided residual binding, while evidence of artificial pigment formation was not found for the 11-cis analogues. Molecular-mechanics-based docking simulations with the crystal structure of rhodopsin have allowed us to rationalize the lack of binding displayed by the 11-cis analogues. Our results indicate that these isomers are highly strained, especially when bound, due to steric clashes with the receptor, and that these interactions are undoubtedly alleviated when 9-cis-5-demethyl-8-methylretinal binds opsin.     

Enantioselective total synthesis and correction of the absolute configuration of megislactone

The title compound, one of the constituents from Iryanthera megistophylla, has been synthesized in enantiopure forms. The stereogenic centers at C-2 and C-3 were constructed by using a chiral auxiliary induced asymmetric aldolization and the C-4 was derived from the corresponding optically active lactates. The carbon-carbon double bond in the side chain was derived from a pure cis vinyl iodide using a Suzuki coupling with an alkyl borane formed in situ from the corresponding terminal alkene. A previously unknown (partial) cis to trans transformation of an isolated C-C double bond in a long alkyl chain was observed during the deprotection of TBS group with CAN. Somewhat unexpectedly, the otherwise undetectable co-presence of the trans isomer of the remote double bond in a long alkyl chain was clearly revealed in ¹H and ¹³C NMR in the presence of a lactone ring. The present work unambiguously shows that the absolute configuration of the natural compound is the antipode of the one originally reported. Some errors in the previous ¹H and ¹³C NMR signal assignments are also corrected.     

TRIS (perfluoroalkylethyl)silyl alkyl amines as calibration standards for electron ionization mass spectrometry in the mass range of 100–3000 Da

A new fluorinated compound mixture has been developed for the calibration of the double focusing mass spectrometer in the mass range of 100–3000 Da in the positive electron ionization (EI) mode. Current calibration standards for EI have either limited mass range [perfluorotributylamine (PFTBA), perfluorokerosene (PFK), s-triazines (TRIS)] or poor peak intensities with significant chemical background in the instrument for several days (perfluoroalkyl phosphazine). The newly synthesized fluorinated silyl alkyl amines mixture is proposed as a reference/calibration standard for EI-MS. This standard produced abundant parent and fragment ions across the entire mass range without any memory effect.     

Isolation of ceramide fractions from skin sample by subcritical chromatography with packed silica and evaporative light scattering detection

Separative method of lipid classes from the stratum corneum was developed with packed silica and supercritical CO2 containing 10% of methanol at 15 degrees C, 15 MPa and 3 ml min(-1). The elution order of lipid classes was first esterified cholesterol, triglycerides, squalene co-eluted in a single peak, then free fatty acids, free cholesterol, ceramides and finally glycosylceramides. The ceramides were eluted in several fractions which depended on the number of hydroxyl groups in the molecule, i.e. more hydroxyl groups were contained in ceramides, more important was the retention. Moreover, the retention was not altered by the presence of carbon double bond and variation of the alkyl chain length. The ceramide response with the evaporative light scattering detector was improved by turning the influence of the solvent nature on the response to advantage. Therefore, addition of various solvents with or without triethylamine and formic acid were tested in post-column due to the incompatibility of such modifiers with silica stationary phase. Thereby the solvent conditions for the separation and the detection can be adjusted almost independently. The response was greatly increased by post-column addition of 1% (v/v) triethylamine and its equivalent amount of formic acid in dichloromethane introduced at 0.1 ml min(-1) into the mobile phase. This device had allowed the detection of 400 ng of ceramide with a S/N = 21, whereas no peak was observed in absence of the post-column addition. Finally, the method was applied to the treatment of skin sample which led to highly enriched ceramide fraction.     

C-H activation of terminal alkynes by tris-(3,5-dimethylpyrazolyl)boraterhodiumneopentylisocyanide: new metal-carbon bond strengths

C-H bond activation of terminal alkynes by [Tp'Rh(CNneopentyl)] (Tp' = hydridotris-(3,5-dimethylpyrazolyl)borate) resulted in the formation of terminal C-H bond activation products Tp'Rh(CNneopentyl)(C≡CR)H (R = t-Bu, SiMe(3), hexyl, CF(3), p-MeOC(6)H(4), Ph, and p-CF(3)C(6)H(4)). A combination of kinetic selectivity determined in competition reactions and activation energy for reductive elimination has allowed for the calculation of relative Rh-C(alkynyl) bond strengths. The bond strengths of Rh-C(alkynyl) products are noticeably higher than those of Rh-C(aryl) and Rh-C(alkyl) analogues. The relationship between M-C and C-H bond strengths showed a linear correlation (slope R(M-C/H-C) = 1.32), and follows energy correlations previously established for unsubstituted sp(2) and sp(3) C-H bonds in aliphatic and aromatic hydrocarbons.     

不同结构烷基苯磺酸盐油水界面扩张粘弹性质

研究了2-甲基-5-(1-庚基辛基)苯磺酸钠、辛基苯磺酸钠和十六烷基苯磺酸钠在正辛烷-水界面上的扩张粘弹性质, 考察了链长变化和疏水基支链化对分子界面行为的影响. 研究结果表明, 链长增加导致分子间相互作用增强, 弹性增大; 疏水支链在界面上可能由于缠绕和变形产生界面慢弛豫过程, 导致较高的扩张模量.     

Prediction and interpretation of infrared intensities of polymethylene chain molecules

We have calculated the IR intensities of some polymethylene chain molecules containing conformational defects or polar heads. Calculations provide spectroscopic markers of end-TG, GTG', GTG, GG and GGTGG defects. Further, a spectroscopical study of interactions between polar heads and alkyl chain is allowed.     

Solid state photopolymerization of acrylic acid at low temperature

Near‐infrared spectroscopy was used to investigate the kinetic characteristics of acrylic acid photopolymerized at ?70°C and room temperature, respectively. The obtained results showed that at ?70°C the double bond conversion increased with increase in the initiator's concentration. Addition of soft chain component polyethylene glycol 400 (PEG400) could lead to high conversion in the solid state, and then high final double bond conversion after post‐curing. The introduction of water at low temperature also contributed largely to the enhancement in the initial and final double bond conversion in solid state. SEM photographs showed that more pores came up in the cured films with the increase in the water content in the reaction system. The change in the photoinitiator concentration, amount of PEG400, and content of water had significant effect on samples cured at lower temperature than at room temperature under the same conditions. Different kinds of photoinitiators showed different contributions to the initial and final double bond conversion on photopolymerization of acrylic acid at low temperature. Significant post‐curing phenomena for photopolymerization of acrylic acid at low temperature could be observed as well. Copyright © 2009 John Wiley & Sons, Ltd.