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Showing papers in "Journal of The Chemical Society-perkin Transactions 1 in 1992"


Journal ArticleDOI
TL;DR: Several precursor polymer routes to poly(p-phenylenevinylene)4, poly[(2,5-dimethyl-pphenylene)vinylene]10 and poly[2, 5-dimethoxy-p -phenylene]15 are described in this paper.
Abstract: Several precursor polymer routes to poly(p-phenylenevinylene)4, poly[(2,5-dimethyl-p-phenylene)vinylene]10 and poly[(2,5-dimethoxy-p-phenylene)vinylene]15 are described. Base induced polymerisation of bis-sulfonium salt monomers afforded the polyelectrolytes 3 and 9 which were converted respectively directly into either polymer 4 or 10. Optimised conditions for the complete displacement of sulfonium groups by methanol to produce the corresponding methoxy precursor polymers 5, 11 and 17 are reported. The fully conjugated polymers obtained after heat and acid treatment of these precursors have been characterised and compared with those obtained via different precursor routes. The 1H NMR spectra of the precursor polymers, as well as IR and UV–VIS data of both the precursor polymers and the materials obtained after conversion into the poly(arylenevinylene)s are discussed.

162 citations


Journal ArticleDOI
TL;DR: In this article, a synthetic lignin dehydrogenation polymer (DHP) of coniferyl alcohol was synthesized and incorporated into a synthetic Lignin de-correlated 2D NMR experiment.
Abstract: Methyl 5-O-(E)-[γ-13C]feruloyl-α-L-arabinofuranoside (FA-Ara) has been synthesized and incorporated into a synthetic lignin dehydrogenation polymer (DHP) of coniferyl alcohol. Inverse-detected long-range C–H correlation NMR experiments on the DHP lignin gave correlation peaks indicative of the copolymerization of the FA-Ara and coniferyl alcohol into the DHP polymer. The bonding sites and modes, as determined by analysis of the carbonyl region of the long-range C–H correlated 2D NMR experiment, are predictable from free-radical coupling mechanisms. In addition to the abundant 4-O-α′ and 4-O-β′ ether couplings, structures involving the β-position of the feruloyl moiety of FA-Ara in β-ether, phenylcoumaran and pinoresinolide structures were present. The incorporation of feruloyl esters into a lignin DHP results in some structures which would not release ferulic acid by solvolytic schemes currently used for quantitation of ferulic acid in plant materials. Thus the degree to which hydroxycinnamic acids are involved in the lignification of forages may be significantly underestimated.

157 citations


Journal ArticleDOI
TL;DR: In this paper, it was shown that Imines 1a and 1b react with dihydrofuran (DHF) under Lewis acid catalysis via Diels-Alder-type addition to form the tetrahydroquinoline derivatives 3a, b, 5, 6, 7a and 8.
Abstract: Imines 1a and 1b react with dihydrofuran (DHF) under Lewis acid catalysis via Diels–Alder-type addition to form the tetrahydroquinoline derivatives 3a, b and 4a, b. Besides these compounds, the methanol adduct 2 of 1a, or 1a in the presence of methanol, gives the methanol-containing tetrahydrofuran derivative 7a and the hexahydrofuro[3,2-b]furan derivatives 5 and 6. In the presence of methanol, 1b gives 3b and 4b, and also 7b and 8. The products 3a, b, 5, 6 and 7a, b originate from approach of the Si(or Re) face of 1a, b onto the Si(or Re) face of DHF; 4a, b and 8 derive from interaction of the Si(or Re) face of 1a, b with the Re(or Si) face of DHF. The dependence of the product distribution on the polarity of the solvent suggests that a concerted mechanism predominates in the former mode and a zwitterionic one in the latter. In the addition of 1a or 2 the mechanistic preference may be exclusive.

125 citations


Journal ArticleDOI
TL;DR: A modification of this synthesis has been employed to prepare a single enantiomer in order to define the absolute configurations of the products.
Abstract: Several C-functionalized cyclohexyldiethylenetriaminepenta-acetic acid derivatives have been prepared from (±)-4-nitrophenylalanine and (±)-trans-cyclohexane-1,2-diamine to produce two sets of diastereoisomeric enantiomers. A modification of this synthesis has been employed to prepare a single enantiomer in order to define the absolute configurations of the products.

114 citations


Journal ArticleDOI
TL;DR: In this paper, the programmed selfassociation of the self-complementary nucleotide-like pyrimidinone 5 and pyrimidine 6, generates, as predicted, organized supramolecular ribbons.
Abstract: The programmed self-association of the self-complementary nucleotide-like pyrimidinone 5 and pyrimidinedione 6, generates, as predicted, organized supramolecular ribbons. The crystal structure of such a species has been determined. A similar entity is obtained from the pyrimidinetriamine 12 with solvent participation, giving a quadruply hydrogen-bonded ribbon, whose crystal structure has also been determined. These processes give access to the designed generation of organized arrays of functional substituents.

111 citations


Journal ArticleDOI
TL;DR: In this paper, the importance of the modular structure of fluor-spacer-amine was pointed out for the design of fluorescent molecular sensors for pH according to the principle of photoinduced electron transfer (PET).
Abstract: The importance of the modular structure ‘fluor-spacer-amine ’is pointed out for the design of fluorescent molecular sensors for pH according to the principle of photoinduced electron transfer (PET). Anthracen-9-yl methylamines (24) and some azacrown ether analogues (15 and 23) are examined in this context. They show pH-dependent fluorescence quantum yields describable by eqn. (5) while all other electronic spectral parameters remain essentially pH-invariant. The range of pKa values of these sensors are understandable in terms of macrocyclic effects and the transmission of electric fields across the anthracene short axis. Phase-shift fluorometric determination of the fluorescence lifetimes of these sensors allows the calculation of the rate constant of PET in their proton-free form to be 1010–1011 s–1, with the diamines 23 and 24b exhibiting the faster rates.

107 citations


Journal ArticleDOI
TL;DR: In this paper, it was shown that radical adducts to nitrone spin traps have been shown to undergo conversion to hydroxyl radical adsducts via nucleophilic substitution reactions; these observations have important consequences for the interpretation of data from EPR/spin-trapping experiments.
Abstract: Radical adducts to nitrone spin traps have been shown, in aqueous solution, to undergo conversion to the hydroxyl radical adduct via nucleophilic substitution reactions; these observations have important consequences for the interpretation of data from EPR/spin-trapping experiments.

90 citations


Journal ArticleDOI
TL;DR: In this paper, the lactam (1R),(4S)-2-azabicyclo[2.1]hept-5en-en-3-one [(−)-2] derived by whole cell enantio-specific hydrolysis of the racemate was converted into (−)-carbovir ( −)-1 in ten steps.
Abstract: The lactam (1R),(4S)-2-azabicyclo[2.2.1]hept-5-en-3-one [(–)-2], derived by whole cell enantio-specific hydrolysis of the racemate was converted into (–)-carbovir (–)-1 in ten steps. Lipase catalysed acetylation of 4-cis-hydroxycyclopent-2-enylmethyl triphenylmethyl ether afforded the optically pure ester (+)-3 and the alcohol (–)-9. The former compound was converted into (+)-carbovir (+)-1 in three steps.

89 citations


Journal ArticleDOI
TL;DR: A versatile approach to dendritic macromolecules with aromatic polyester inner structure and a readily modified hydrophobic/hydrophilic ‘surface’ is described, which allows for subsequent selective removal of the numerous benzyl ether chain ends by hydrogenolysis to afford a dendrites with phenolic chain ends.
Abstract: A versatile approach to dendritic macromolecules with aromatic polyester inner structure and a readily modified hydrophobic/hydrophilic ‘surface’ is described. The polyester fragments are prepared by a convergent growth process involving 3,5-bis(benzyloxy)benzoic acid as the ‘surface’ or chain-ending moiety and trichloroethyl 3,5-dihydroxybenzoate as the monomer unit. The key esterification step is accomplished in high yield using dicyclohexylcarbodiimide and 4-dimethylaminopyridinium toluene-p-sulfonate as condensing agents. The coupling step is followed by activation of the new focal point by removal of the trichloroethyl ester group with zinc-acetic acid. Repetition of this two-step process leads to large dendritic fragments that may be coupled to a polyfunctional core to complete the dendritic macromolecule. The chemistry chosen for this synthesis allows for subsequent selective removal of the numerous benzyl ether chain ends by hydrogenolysis to afford a dendritic macromolecule with phenolic chain ends. Further modification of the chain ends is readily accomplished in processes that effectively transform the initially hydrophobic dendritic molecule into one that is both hydrophilic and water-soluble. These transformations of the ‘surface’ functionalities are also accompanied by drastic changes in glass transition behaviour.

85 citations


Journal ArticleDOI
TL;DR: In this paper, an efficient approach to the asymmetric synthesis of phosphorus analogues of dicarboxylic α-amino acids is described, which consists in the reaction of the nickel(II) complex (4) of the Schiff's base derived from (S)-o-[(N-benzylprolyl)amino]benzophenone 3 and glycine with the appropriate alkyl halide, substituted with an alyilphosphonate group.
Abstract: An efficient approach to the asymmetric synthesis of phosphorus analogues of dicarboxylic α-amino acids is described. The method of choice consists in the reaction of the nickel(II) complex (4) of the Schiff's base derived from (S)-o-[(N-benzylprolyl)amino]benzophenone 3 and glycine with the appropriate alkyl halide, substituted with an alkylphosphonate group. The reactions were carried out in MeCN at 25 °C, with solid KOH as a catalyst. Michael-type base-catalysed addition of vinyl-phosphonate and vinylphosphinate to complex 4 in dimethylformamide (DMF) at 50–70 °C could also be employed. Significant diastereoselectivity (90% d.e.) was observed for the alkylation of complex 4. Optically pure (S)-phosphinothrieine, (S)-2-amino-3-phosphonopropanoic acid, (S)-2-amino-4-phosphonobutanoic acid and (S)-2-amino-5-phosphonopentanoic acid were obtained after the alkylated diastereoisomeric complexes had been separated on SiO2 and hydrolysed with aq. HCl. The initial chiral reagent 3 was recovered (60–85%). Novel amino acids 9, having free carboxy groups and esterified phosphonic and phosphinic groups, could also be obtained as intermediates due to the mild conditions of the decomposition of the alkylated diastereoisomeric complexes.

84 citations


Journal ArticleDOI
TL;DR: In this paper, the distribution coefficients of free α-amino acids have been measured around their isoelectric value by centrifugal partition chromatography (CPC), allowing the determination of the partition coefficient (log P) of the amino acids in their zwitterionic form.
Abstract: The distribution coefficients of free α-amino acids have been measured around their isoelectric value by centrifugal partition chromatography (CPC), allowing the determination of the partition coefficient (log P) of the amino acids in their zwitterionic form. Good correlations with published distribution coefficients of amino acid derivatives allowed log P values to be calculated for the five amino acids (Arg, Asn, Asp, Glu, Lys) whose high polarity prevented direct measurements by CPC. The log P values were factorized into a steric component (molecular volume V, mainly accounting for inductive and hydrophobic forces) and a polarity factor (Λ, accounting for ion–dipole and dipole–dipole interactions and hydrogen-bonds) which correlates with other amino acid parameters expressing mainly polar interactions. Using two examples from the literature, we show that multiple linear regression analysis based on steric and polar parameters is able to afford a quantitative interpretation of factors influencing protein conformational stability.

Journal ArticleDOI
TL;DR: The structure of monatin, a high-intensity sweetener isolated from Schlerochiton ilicifolius, was elucidated by 1H and 13C NMR spectroscopy as 4-hydroxy-4-(indol-3-ylmethyl)glutamic acid as discussed by the authors.
Abstract: The structure of monatin, a high-intensity sweetener isolated from Schlerochiton ilicifolius was elucidated by 1H and 13C NMR spectroscopy as 4-hydroxy-4-(indol-3-ylmethyl)glutamic acid. The 2R*,4R* relative configuration of the two chiral centres in monatin was determined by NOE studies on a derivative, methyl 2-(indol-3-ylmethyl)-4-(2,4-dinitroanilino)-5-oxo-2,3,4,5-tetrahydrofuran-2-carboxylate. The assignment of the 2S configuration to monatin, through application of the Clough–Lutz–Jirgenson rule, established the 2S,4S configuration for the compound.

Journal ArticleDOI
TL;DR: The structures of two phytotoxins, syringomycin and syringotoxin, produced by Pseudomonas syringae pv. syringa, were determined as mentioned in this paper.
Abstract: The structures of two phytotoxins, syringomycin and syringotoxin, produced by Pseudomonas syringae pv. syringae, were determined. Several amino acid residues of syringomycin were different from those in the syringostatins. Syringotoxin B proved to be [Gly3]syringostatin A. The three kinds of phytotoxins showed close structural similarity, and the stereochemistry of their components was deduced and compared.

Journal ArticleDOI
TL;DR: In this paper, an LSER analysis of log P for the critical quartet of solvent systems has been carried out using, as initial variables, VI for volume, µ2 for dipolarity, and proton donor ∑α and acceptor βf scales based on log Kα and log Kβ respectively.
Abstract: An LSER analysis of log P for the ‘critical quartet’ of solvent systems has been carried out using, as initial variables, VI for volume, µ2 for dipolarity, and proton donor ∑α and proton acceptor βf scales based on log Kα and log Kβ respectively A common data matrix and an unprecedented range of functionalities have been employed By making the analysis stepwise, starting with the simplest solutes and adding more in order of increasing complexity, we have been able to identify hitherto unrecognised variables and ‘fine-tune’ established ones in such a way as to derive self-consistent proton donor and acceptor values applicable to the whole range of solvent systems By this ‘LSER in reverse’ we have established, inter alia, the following new facts: (a)βf possesses a constant effective zero whereas that for ∑α is solvent-sensitive; (b) a new term nβf is required for acceptor solutes with two or more available lone pairs; (c) when neither lone pair is available, the acceptor strength of carbonyl is sharply reduced; (d) a second term specific to NH2 is required for ∑α in alkane and chloroform; (e) there is mutual shielding of XH and one lone pair in structures such as CO2H and CONH2; (f) ureas and other structures with parallel NH functions are proton donors of exceptional strength; (g) the acceptor ability of dipolar bases (PO and SO) varies with the solvent systemCooperativity in solute–solvent bonding exists but takes complex forms, and does not appear strong enough to account eg for the hydrogen bonding properties of bulk water and the alcohols, for which mass action appears a likelier explanation We present evidence (see Appendix) that mass action will most probably explain certain well known anomalies in the apparent proton acceptor ability of water as revealed by partitioning studiesThe present results throw new light on previously anomalous octanol–water log P values and can predict f-values for other solvent systems Most importantly, they provide new information not only on the strength of hydrogen bonding for more than 60 functional groups, but also on its directionality: we are able to predict, with reasonable certainty, which XH groups and lone pairs are actually available for bonding This information is applicable to water, other solvents, and by implication to the biophase, so should find direct and immediate use in rationalising and quantifying drug–receptor interactions

Journal ArticleDOI
TL;DR: The hydrogen-bonding fixation site is the carbonyl group, even for the very hindered amide ButCON(C6H11)2 as discussed by the authors, and the hydrogen bonding basicity is increased by six-membered cyclisation.
Abstract: The hydrogen-bond basicity scale pKHB(logarithm of the formation constant of 4-fluorophenol–base complexes in CCl4) has been measured for tertiary and secondary amides, carbonates, ureas and lactams. The hydrogen-bonding fixation site is the carbonyl group, even for the very hindered amide ButCON(C6H11)2. In the amides R1CONR2R3 the hydrogen-bond basicity is decreased more by bulky R1 substituents on the carbonyl carbon than by bulky R2 and R3 substituents on nitrogen. The field effect of X substituents operates more effectively on hydrogen-bond basicity than the resonance effect in the XCONMe2 series. The hydrogen-bond basicity is increased by six-membered cyclisation.

Journal ArticleDOI
TL;DR: In this article, it was shown that in the merocyanine isomer complexing an alkali metal ion, especially Li+, the crown-complexed metal ion interacts intramolecularly with the phenolate anion, thus being bound more powerfully than that in a corresponding spiropyran isomer, owing to anion.
Abstract: Spirobenzopyran derivatives carrying a monoazacrown moiety, such as 12-crown-4, 15-crown-5, and 18-crown-6 moieties, and their acyclic analogue, at the 8-position have been synthesized. Alkali metal ion complexation by the crowned spirobenzopyrans, followed by isomerization to the corresponding merocyanine form, and their photoisomerization, have been studied by cation extraction, absorption spectroscopy, and NMR spectroscopy. Binding of alkali metal ions (Li+, Na+ and K+) by the crown moieties leads to isomerization of the crowned spirobenzopyrans even under dark conditions. 7Li and 23Na NMR spectroscopy suggest that in the merocyanine isomer complexing an alkali metal ion, especially Li+, the crown-complexed metal ion interacts intramolecularly with the phenolate anion, thus being bound more powerfully than that in the corresponding spiropyran isomer, owing to anion, thus being bound more powerfully than that in the corresponding spiropyran isomer, owing to an additional-binding-site effect. UV-light irradiation in tetrahydrofuran further promotes the isomerization to the merocyanine form, the thermal stability of which depends significantly not only on the ion selectivities of their crown moieties but also on the ease of the intramolecular interaction between the crown-complexed metal ion and the phenolate anion. Under visible-light irradiation, the cation-bound merocyanine form readily reverts to the spiropyran form, releasing the metal ions to some extent. Alternating irradiation with UV and visible light or turning-on and -off of visible light, therefore, causes the isomerization of crowned spirobenzopyrans even in the presence of alkali metal ions, in turn affording control of their cation-complexing abilities.

Journal ArticleDOI
TL;DR: The 4-acyloxybenzyl phosphoesters provide the first example of a protecting group which will enable the bioactivation of phosphonate prodrugs at rates appropriate to biological systems as discussed by the authors.
Abstract: The di(4-acetoxybenzyl) ester of methylphosphonate 4(X = H, R = Me) and the di(4-acyloxybenzyl) esters of methoxycarbonylmethylphosphonate 4(X = MeO2C, R = Me, Et, Pr, Pri, Bu or But) were prepared from the appropriate benzyl alcohol and phosphonic dichloride. At pD 8.0 and 37 °C, both series of compounds hydrolyse with half-lives greater than 24 h to the corresponding mono(4-acyloxybenzyl) esters 5(X = H or MeO2C, R = Me, Et, Pr, Pri Bu or But) which were prepared by treatment of the di(4-acyloxybenzyl) esters 4 with sodium or lithium iodide. The mono(4-acyloxybenzyl) esters 5(X = H, R = Me) and 5(X = MeO2C, R = Me, Et, Pr, Pri or But) undergo chemical hydrolysis to methylphosphonate 6(X = H), and methoxycarbonylmethylphosphonate 6(X = MeO2C) respectively, together with 4-hydroxybenzyl alcohol and the appropriate acylate anion. The rates of hydrolysis of the mono(4-acyloxybenzyl) esters decrease as the length and steric bulk of the acyl group increases, with half-lives ranging from ∼ 150 h for the acetyl analogues to 2240 h for the pivaloyl derivative. The hydrolyses of the di- and mono-(4-acyloxybenzyl) esters were catalysed by porcine liver carboxyesterase (PLCE), and in all cases the acylate anion was formed. The rate of enzymatic hydrolysis was most rapid for the 4-butanoyloxybenzyl and 4-isobutanoyloxybenzyl analogues. The methoxycarbonyl ester of the phosphonoacetate analogues was not cleaved by PLCE. The methylphosphonate generated from the reaction of 4(X = H, R = Me) in the presence of esterase and H218O, did not contain 18O attached directly to phosphorus. These results suggest that both the chemical and enzymatic hydrolyses of the mono(4-acyloxybenzyl) esters and the PLCE-catalysed hydrolyses of the di(4-acyloxybenzyl) esters proceed via hydrolysis of the acyl group to give the acylate anion and the unstable 4-hydroxybenzyl esters. The electron-donating 4-hydroxy group facilitates the cleavage of the benzyl-oxygen bond with the formation of the 4-hydroxybenzyl carbonium ion 9, which readily reacts either with water or the phosphate buffer. The 4-acyloxybenzyl phosphoesters provide the first example of a protecting group which will enable the bioactivation of phosphonate prodrugs at rates appropriate to biological systems.

Journal ArticleDOI
TL;DR: Water-stable axial dialkoxy hypervalent phosphorus(V)tetraphenylporphyrins have been synthesized in a novel fashion by efficient substitution of axial chloride ligands of dichlorophosphorus(V)-tetrabhenyl porphyrin this article.
Abstract: Water-stable, axial dialkoxy hypervalent phosphorus(V)tetraphenylporphyrins have been synthesised in a novel fashion by efficient substitution of axial chloride ligands of dichlorophosphorus(V)-tetraphenylporphyrin.

Journal ArticleDOI
TL;DR: In this paper, the relative stability of four conformers and thermodynamic parameters for interconversion among 4 conformers of 25,26,27,28-tetramethoxycalix[4]arene (1a) and 5,11,17,23-Tetra-tert-butyl-25,26.27, 28, 28tetramerethoxyalix[ 4]arenes (1b) have been determined by 1H NMR spectroscopy.
Abstract: Relative stabilities of four conformers and thermodynamic parameters for interconversion among four conformers of 25,26,27,28-tetramethoxycalix[4]arene (1a) and 5,11,17,23-tetra-tert-butyl-25,26,27,28-tetramethoxycalix[4]arene (1b) have been determined by 1H NMR spectroscopy. The relative stability of 1a is in the order partial cone (most stable) > cone > 1,2-alternate and 1,3-alternate (undetected) and that for 1b is in the order partial cone (most stable) > cone > 1,2-alternate > 1,3-alternate (least stable). These orders are reproduced well by MM3, in contrast with MM2. In particular, the energy differences between partial cones and cones computed by MM3 (0.27 kcal mol–1 for 1a and 1.50 kcal mol–1 for 1b) show good agreement with those determined by 1H NMR spectroscopy (0.32 ± 0.13 kcal mol–1 for 1a and 1.2 ± 0.3 kcal mol–1 for 1b). Both the computational and the spectroscopic results suggest that the basic skeletons for cones, 1,2-alternates and 1,3-alternates are relatively rigid (sharp potential energy surfaces) whereas that for partial cones is more or less flexible (flattened potential energy surface). Thus, introduction of the tert-butyl groups into the para-positions destabilizes cones and 1,2-alternates because it is difficult to reduce the increased steric crowding by the conformational change. In 1,3-alternates four phenol units are parallel, so that introduced tert-butyl groups would increase the steric crowding to a lesser extent. The basic skeleton for partial cones changes significantly upon introduction of tert-butyl groups, indicating that the increased steric crowding is relaxed by the conformational change. The finding clearly explains why partial cones frequently appear as the most stable conformer.

Journal ArticleDOI
TL;DR: In this article, the cation complexing abilities of a series of p-tert-butylcalix[4]arenes bearing ligating ester groups in the cone conformation have been assessed by stability constant measurements in methanol and extraction studies from water into dichloromethane.
Abstract: The cation complexing abilities of a series of p-tert-butylcalix[4]arenes bearing ligating ester groups in the cone conformation have been assessed by stability constant measurements in methanol and extraction studies from water into dichloromethane. The cations studied were Na+ and K+ and variations in the ester function (CO2R) included R = methyl, ethyl, n-butyl, tert-butyl, benzyl, phenyl, phenacyl, methoxyethyl, trifluoroethyl, methylthioethyl and prop-2-ynyl. The effect of replacing one or two ester functions in the tetraethyl ester by methyl ester, carboxylic acid, ketone and amide functions was also studied. Selectivities for Na+ relative to K+ in stability constants range from 2 to 2500, the phenacyl derivative having the highest selectivity. X-Ray diffraction analysis was used to probe the conformation of the trifluoroethyl ester 11. Crystals of 11 are monoclinic, space group P21/n, in a cell of dimensions a= 13.987(2), b= 16.194(3), c= 27.630(5)A; β= 98.70(1)°; R= 0.077 for 3172 observed data. The compound possesses a distorted cone conformation.

Journal ArticleDOI
TL;DR: In this article, a data matrix has been prepared of log P values for 103 compounds distributed across four highly contrasted solvent-water partitioning systems: the critical quartet of octanol (amphiprotic), alkane (inert), chloroform (proton donor) and propylene glycol dipelargonate (PGDP; proton acceptor).
Abstract: A data matrix has been prepared of log P values for 103 compounds distributed across four highly contrasted solvent–water partitioning systems: the ‘critical quartet’ of octanol (amphiprotic), alkane (inert), chloroform (proton donor) and propylene glycol dipelargonate (PGDP; proton acceptor). Here ‘alkane’ is defined as the straight-chain sequence from hexane to octane and (possibly) higher; it is shown that cyclohexane is out of line. In principle, these log P values can now be used to construct a comparative table of fragment values (f-values) for all four systems. In practice, those for non-polar substituents must first be established. Here the key quantity is f(CH2). This has been re-determined, and in the process its variability rationalised, for 24 water-saturated solvent systems; here the key factors (dry solvents are different) turn out to be the molarity, in the organic phase, of water and the solvent's own functional group. There results an almost complete data matrix of 82 f-values for all four solvents, about 25% of which are derived from the linear solvation energy relationship (LSER) equations of Part 3.7 It is shown that these four sets are very distinct, a fact that misleading statistical treatments can easily disguise. How the medicinal chemist might use these contrasting data sets is critically discussed, with particular reference to the rationalisation of biological selectivity.

Journal ArticleDOI
TL;DR: In this article, the EPR spectra of RC60C60R were analyzed and it was shown that 2/3 of the unpaired spin population is located on the three carbon atoms ortho to that bearing the incoming radical R.
Abstract: Alkyl radicals generated in solution by UV photolysis add to C60 to form adducts of the type RC60, whose EPR spectra are discussed. When R = CCl3, CBr3, tert-butyl or 1-adamantyl, the spectrum is sufficiently powerful to permit the detection of several 13C satellites associated with the C60 component of the free radical. It is concluded from the intensities and hyperfine interactions of these satellites that ca. 2/3 of the unpaired spin population is located on the three carbon atoms ortho to that bearing the incoming radical R.There is evidence from the temperature dependence of the EPR spectra of certain RC60 radicals that they exist in equilibrium with their dimer, RC60C60R. For R = isopropyl, tert-butyl, 1-adamantyl and CCl3, the enthalpy of dissociation is 35.5, 22.0, 21.6 and 17.1 kcal mol–1 respectively.

Journal ArticleDOI
TL;DR: The conformation and biological activity of the synthetic gramicidin A and B analogues have been studied and α-helical motifs can be clearly distinguished in analogues, but the CD spectra show inherent complexities.
Abstract: In an attempt to mimic the stable helical structures of proteins with possible pore-forming ability in membranes, the linear gramicidin backbone has been changed by inserting achiral α-aminoisobutyric acids (Aib) in place of all of the alternatively sequenced D-amino acids. The conformation and biological activity of the synthetic gramicidin A and B analogues have been studied. CD measurements have been used to determine the conformation in solution. The original conformation of gramicidin clearly changes and its antimicrobial activity is reduced in Aib analogues. Although α-helical motifs can be clearly distinguished in analogues, the CD spectra show inherent complexities. The possibility of superposition of different conformations is considered. The potential pore-forming ability of analogues is briefly discussed.

Journal ArticleDOI
TL;DR: In this article, the electron acceptor properties of X-Pyridinium (X-Py)+ via an electrochemical reduction potential (EPc) were evaluated and it was shown that X-Py+ is strong electrophiles in their charge transfer interaction with aromatic donors to produce cofacial acceptor-donor pairs.
Abstract: X-Pyridinium cations with N-heteroatomic substituents such as X = halogen, nitro, alkoxy and acyloxy (i.e., X-NC5H5+), in common with the ubiquitous N-alkylpyridinium cations, interact spontaneously with different benzene, naphthalene and anthracene donors (ArH) to afford a series of 1 : 1 charge-transfer complexes showing characteristic absorption spectra in the visible region. Quantitative evaluation of the electron-acceptor properties of X-Py+(via an electrochemical reduction potential Epc) indicates that the N-nitropyridinium (Epc=+0.10 V), N-fluoropyridinium (Epc=–0.66 V), N-acetoxypyridinium (Epc=–0.81 V), and N-methoxypyridinium (Epc=–1.02 V) cations are strong electrophiles in their charge-transfer interaction with aromatic donors to produce cofacial acceptor–donor pairs [X–Py+, ArH] that are structurally related to the more common N-methylpyridinium (Epc=–1.32 V) analogues.

Journal ArticleDOI
TL;DR: In the absence of light and electron donors, hypericin displays an EPR signal which is attributed to a semiquinone-like radical, formed by intermolecular electron transfer as discussed by the authors.
Abstract: Hypericin, a potent antiviral agent, displays, in the absence of light and electron donors, an EPR signal which is attributed to a semiquinone-like radical, formed by intermolecular electron transfer. On irradiation with visible light the amplitude of the EPR signal increases significantly. This increase is highest (ca. 20 fold) in aqueous dispersions of the lysine salt of hypericin. Irradiation of hypericin water aggregates in the presence of oxygen generates superoxide radicals which may be registered by the spin trap technique.This finding implies that the free radicals of hypericin and superoxide radicals formed on photoirradiation of hypericin may play a hitherto unrecognized role in the biological activities elicited by hypericin both in vivo and in vitro.

Journal ArticleDOI
TL;DR: The synthesis of unsymmetrical biphenyls 10 and 25 has been carried out by the palladium(0) catalysed coupling of the aryl boronic acid derivatives 5 and 20 with the bromides 9 and 23 derived from (R)-4-hydroxyphenylglycine and (S)-tyrosine.
Abstract: The synthesis of the unsymmetrical biphenyls 10 and 25 has been carried out by the palladium(0) catalysed coupling of the aryl boronic acid derivatives 5 and 20 with the aryl bromides 9 and 23 derived from (R)-4-hydroxyphenylglycine and (S)-tyrosine. In the former case unsuccessful attempts were made to bring about cyclization to compound 4 which is an analogue of the biphenyl ring system found in vancomycin. In the latter case, a variety of cyclization methods were used to give the cyclic products 34 and 35 which are analogues of the biphenomycin antibiotics.

Journal ArticleDOI
TL;DR: The amino alcohols HO(CH2)n NH2(n= 2, 3 and 5) react readily with ethyl (Z)-N-(2-amino-1,2-dicyanovinyl)formimidate 5 to give the amidines 6a-c, which cyclize in the presence of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) to give corresponding 4-(cyanoformimidoyl)imidazole-5-amines 7a
Abstract: The amino alcohols HO(CH2)n NH2(n= 2, 3 and 5) react readily with ethyl (Z)-N-(2-amino-1,2-dicyanovinyl)formimidate 5 to give the amidines 6a-c, which cyclize in the presence of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) to give the corresponding 4-(cyanoformimidoyl)imidazole-5-amines 7a-c, which can be isolated in the cases where n= 2 or 3.In the presence of aldehydes and ketones, the imidazoles 7a-d lead to the 6-carbamoyl-1,2-di-hydropurines 9a-f which, in some cases, are oxidised to the corresponding 6-carbamoylpurines.The reaction of the imidate 5 with 2-methoxyethylamine leads to the amidine 6d and, on treatment with DBU, the reactive imidazole 7d which can be used directly for further reaction.

Journal ArticleDOI
TL;DR: The kidney of the giant clam Tridacna maxima contains algal arsenic compounds, probably as a consequence of the clam's symbiotic relationship with unicellular algae (zooxanthallae) as discussed by the authors.
Abstract: The kidney of the giant clam Tridacna maxima contains algal arsenic compounds, probably as a consequence of the clam's symbiotic relationship with unicellular algae (zooxanthallae). Extraction of Tridacna kidneys yielded three novel arsenic compounds, N-(5′-deoxy-5′-dimethylarsinoyl-β-D-ribosyloxycarbonyl)glycine 5, (2S)-3-(5′-deoxy-5′-dimethylarsinoyl-β-D-ribosyloxy)-2-hydroxypropanoic acid 4a, and (2R)-3-(5′-deoxy-5′-dimethylarsinoyl-β-D-ribosyloxy)-2-hydroxypropanoic acid 4b, in addition to four previously reported dimethylarsinoylribosides. The structures of the three new Compounds were assigned chiefly from NMR data, and those for compounds 4a and 4b were confirmed by synthesis. Extraction of a second batch of Tridacna kidneys gave, in addition to compounds identified in the first extraction, (2S)-3-[(5′-deoxy-5′-trimethylarsonio-β-D-ribosyloxy)-2-hydroxypropyl]sulfate 18 and two novel compounds: an arsenic-containing nucleoside, 9-(5′-deoxy-5′-dimethylarsinoyl)-9H-adenosine 16 and N-[4-(dimethylarsinoyl)butanoyl]taurine 21. Syntheses of compounds 16 and 21 are reported. The presence of the nucleoside 16 in Tridacna, as a consequence of algal metabolism, supports a proposed pathway for the biogenesis of arsenic-containing ribosides by algae involving methylation and adenosylation by S-adenosylmethionine. A biogenetic pathway for compound 21 involving donation of the 3-amino-3-carboxypropyl moiety of S-adenosylmethionine is also proposed. The presence of both compounds 16 and 21 in Tridacna may represent the first example of donation, by S-adenosylmethionine, of all three of its alkyl groups to a single acceptor (arsenic) within one organism.

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TL;DR: A survey of a series of organosilyl derivatives of serine and tyrosine has shown that they have a satisfactory stability profile for use in peptide synthesis as discussed by the authors.
Abstract: A survey of a series of organosilyl derivatives of serine and tyrosine has shown that they have a satisfactory stability profile for use in peptide synthesis. Only when alkaline conditions were used did side-reactions appear. A range of stability profiles have been determined from a study of organosilyl derivatised dipeptides under different conditions, giving t½-values for hydrolysis ranging from 41 to 465 min in acid conditions, yet giving long-term stability at pH-values near to neutrality.

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TL;DR: In this article, 1,6-Anhydro-2,azido-2-deoxy-β-D-glucopyranose has been prepared by a two-step procedure from Dglucal and transformed into precursors useful in the synthesis of oligosaccharides.
Abstract: 1,6-Anhydro-2-azido-2-deoxy-β-D-glucopyranose has been prepared by a two-step procedure from D-glucal and transformed into precursors useful in the synthesis of oligosaccharides.