Browsing by Subject "Organic Chemistry"

Now showing 1 - 15 of 15
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    Chemical and spectroscopic studies of the capsular polysaccharides of some Klebsiella serotypes
    (1988) Ravenscroft, Neil; Stephen, A M
    As part of an international collaborative programme concerned with the elucidation of the molecular structures of capsular polysaccharides (the K-antigen) produced by strains of the bacterial genus Klebsiella, the capsular material of serotype K71 has been investigated, and that of serotypes K36 and K64 re-examined, by novel enzymic and spectroscopic methods. The cultivation and employment of bacteriophages which are capable of cleaving (by specific glycanase action) the isolated, cognate bacterial polysaccharide in vitro has yielded highly significant oligosaccharides. These may represent the repeating unit in the polysaccharide or be derivatives resulting from conversion of uronic acid to the 4,5-unsaturated analogue where, as found for serotype K64, the mode of cleavage is β-elimination not hydrolysis. The oligosaccharides thus generated have proved to be far more amenable to chemical and spectroscopic studies than their parent polymers, thereby facilitating complete characterisation of the molecular structures of the original polysaccharides. Chemical methods applied to these oligosaccharides included specific degradations by periodate oxidation and acid-, alkali- or enzyme- catalysed hydrolysis, products being identified by methylation analysis (involving the extensive use of gas-liquid chromatography coupled to mass spectrometry) and spectroscopic studies (mass and n.m.r.). During the course of these investigations it became apparent that the structures of the intact oligosaccharides (containing six or seven sugar residues) could be determined almost entirely from spectroscopic analysis, chiefly by detailed two-dimensional n.m.r. studies involving the use of high field spectrometers and the application of homo- and heteronuclear shift correlated spectroscopy, the sequence of sugar units being confirmed by mass spectrometric analysis of the permethylated derivatives. Methylation analysis of the oligosaccharides derived from Klebsiella serotype K36 proved that the glucuronic acid residue is linked through 0-2, and not 0-4 as published by others; this finding was corroborated during characterisation of the monomeric oligosaccharide by mass- and n.m.r. spectroscopy. Bacteriophage φ64 was shown to cleave the cognate K64 exopolysaccharide by a β-elimination process; the resulting hex-4-enuronic acid, present as a terminal group in the derived oligosaccharide was fully characterised by hydrogenation and g.l.c.-m.s. of acetylated products, and by detailed n.m.r. studies including long-range heteronuclear experiments. Finally the structure of the heptasaccharide repeating unit of the Klebsiella K71 capsular polysaccharide was established by spectroscopic analysis of the oligosaccharides derived by bacteriophage φ71 cleavage of the polymer; features of the proposed structure were confirmed by chemical degradation studies performed on the native polysaccharide.
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    Dimethyl N-Aryl phosphoramidates : structural effects on bonding and solvolytic reactivity
    (1981) Rijkmans, Bloys Peter; Modro, Tom A
    The acid catalysed hydrolysis of a number of ring alkyl substituted dimethyl N-aryl phosphoramidates, (MeO)2P(0)NHAr, has been studied by measuring the rates of hyd~olysis with the aid of a UV spectrophotometer. These rates have been correlated with the pKa values of the corresponding ani I inium iOhs and the slope of this reactivitybasicity relationship for phosphoramidate with ortho substituents (6 = 0~85) is found to differ from that for substrates with meta and para substituents (S = 0,36). Determination of the thermodynamic parameters indicates that the entropy of activation is approximately constant for the substrates studied and the strongly negative values ~ -I -I (~S = 155,4 - 17,5 J mole K ) are consistent with an A2 type mechanism.
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    The electrophilicity and chemistry of phosphate esters
    (1986) Cocks, Sarah; Modro, Tom A
    A series of phosphate esters containing the E.-nitrophenyl moiety as a leaving group were synthesised and their base catalysed hydrolysis and electron impact-induced fragmentations studied. Heterocyclic ester substituents were present in some of the substrates and in-this sense they were considered as models for a nucleotide molecule containing both the 11 energy-rich11 phosphate bond and the nitrogen heterocyclic ring. The relative reactivity of the phosphorus-E,-nitrophenoxide bond was taken as a probe for nitrogen (pyridyl or quinolyl) participation in the substitution reaction. Although the heterocyclic derivatives show that the introduction of the nitrogen centre increases the rate of base catalysed hydrolysis, the reactivity enhancement is. not significant and results probably from polar effects rather than from intra-molecular catalysis. A comparison of the mass spectra of the heterocyclic and carbocyclic analogues, reveal differences which are significant (in the pyridyl substrates) and dramatic (in the quinolyl substrate) with regard to the fragmentation involving the E.-nitrophenoxy radical expulsion and formation of the corresponding phosphorylium ion. Synthetic approaches towards dimethylaryl and dimethyl(arylalkyl) phosphates are discussed. Nucleophilic displacement at the methyl ester carbon, and in particular the oxygen+ nitrogen methyl group transfer in these substrates occurs readily, complicating the synthetic procedures and lowering the stability of products. Dimethyl-(2-pyridylmethyl) phosphate isomerises in water to the zwitterionic N-methylpyridinium derivative via bimolecular methylation. The kinetics of the reaction were studied and no evidence for intra-molecular methyl transfer was obtained. - ii - The isomerisation of dimethyl-(quinolin-8-yl) phosphate in water also provides evidence for the bimolecular methylation. The crystal and molecular structure of dimethyl-(quinolin-8-yl) phosphate was determined and has revealed that the orientation of the CH 3 groups in the crystal provide no indication for the occurrence of methyl transfer in the solid state. The dynamics of the prepared phosphate derivatives studied in solutions were also investigated by means of mass spectrometry. Fragmentation patterns and their relative contributions are presented and discussed. The effect of solvent on the rates of the reaction between trimethyl phosphate and i) pyridine and ii) 4-(dimethylamino)pyridine, was studied at 25 - 65°C using NMR techniques. The solvents used were DzO, CD30D, CD3CN and DzO/CD30D and DzO/CD3CN mixtures. Water (DzO) is the most effective medium for the methyl transfer reaction. We attribute this to the strong hydrogen bonding between water and the departing dimethyl phosphate anion in the transition state. Activation parameters obtained for the reactions in pure solvents confirmed our interpretation of the hydrogen bonding effect operating in the transition state. Fragmentation of S-arylethyl phosphates has been investigated. A novel feature is exhibited by S-arylethyl phosphorochloridates. They easily decompose thermally yielding 1-chloro-2-arylethanes and/or arylethylenes presumably via concerted C-O and P-Cl bond fission involving a phenonium ion intermediate and expulsion of a metaphosphate species.
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    Novel quinone syntheses
    (1976) Roos, Gregory Harold Pelteret; Giles, R G F
    As indicated by the title, this dissertation deals with the investigation of the syntheses of a number of novel quinones. Chapter I deals with the syntheses of quinonoid derivatives of the compounds isobenzofuran and isoindole. These are the parent species of that series of heterocyclic compounds which contain a single heteroatom and are isoelectronic with naphthalene. They have been of considerable interest to workers in recent years, but have proved to be relatively unstable. We have therefore set out to prepare stable quinonoid derivatives of these. In Chapter II we have sought to develop, via regiospecific Diels-Alder additions, simple syntheses of some synthetically useful napthaquinonoid systems. The formation of many of these, required in the past as intermediates for the syntheses of a number of naturally occurring quinones, has previously proved tedious. Tae study of these addition reactions has afforded a direct route for the synthesis of the natural quinone, droserone. Finally, in Chapter III, some of the napthaquinones produced in Chapter II have been employed as intermediates in the syntheses of certain naturally occurring quinonoid species. These include a caryopterone and model compounds for the proposed syntheses of the anti biotics, Juglomycins A and B.
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    Novel tetracyclic structures from the synthesis of thiolactone-isatin hybrids
    (2010) Chibale, Kelly; Su, Hong; Hans, Renate Hazel
    A simple and straightforward synthetic approach to potential anti-infective thiolactone-isatin hybrids led to the discovery of novel tetracyclic compounds which bear a macrocylic motif containing an unusual bridged amide bond.
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    Some aspects of quinonoid chemistry
    (1979) Mitchell, Peter Robert King; Giles, R G F
    The first part of this thesis deals with the attempts made to synthesise 4 - hydroxypiloquinone. The proposed synthesis involved the making of two correctly substituted aromatic moieties that could be joined together to give a stilbene, which on irradiation would give a phenanthrene, that could be further elaborated to give a suitable precursor to 4 - hydroxypiloquinone. All attempts to convert the precursor to the required quinone were unsuccessful. In the second part of this thesis, a number of 2 - acetyl - 3 -alkylamino - 6 - anilino - 1,4 - benzoquinones were prepared by the reaction of 2 - acetyl - 3,6 - dianilino - 1,4 - benzoquinone with alkylamines in chloroform. Irradiation of these alkylamino - p -benzoquinones with ultra-violet light gave benzoxazoles where an á -hydrogen atom was present in the alkylamino substituent, except for the cyclohexylamino - and s - butylamino - benzoquinones which gave an unstable photo-product. With t - butylamino - benzoquinone no photoreaction was observed.
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    The structure and reactivity of N-Acyl phosphoric amides and related systems
    (1983) Mizrahi, Valerie; Modro, Tomasz A
    Two synthetic approaches towards the N-acyl phosphylamide system Z₂P(O)-NR-C(O)R' (1; Z =alkyl, O-alkyl; R = H, Me; R' =M e, Ph), from phosphylamide and carboxamide precursors are discussed. The infrared, ¹H and ¹³C NMR spectral features of system (1), indicate predominant resonance interaction of the nitrogen non-bonding electrons with the adjacent carboxyacyl, rather than phosphacyl centre. The electron-with- drawing effect of the phosphyl substituent Z₂P(O), is nonetheless sub- stantial, thus weakening the basicity and nucleophilicity of the nitrogen atom and enhancing the electrophilicity of the carbonyl centre. The influence of the electronic distribution within the OPNCO moiety upon the structure and reactivity of (1), has been investigated.
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    Structure and synthesis of some phosphorus compounds of potential biological activity
    (1988) Kyriacou, Panos; Modro, Tomasz A; Paterson-Jones, Colin J
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    Studies directed towards the synthesis of metal-containing ketones
    (1977) Davidowitz, Bette; Cragg, G M L; Haines, Raymond J
    The photochemistry of organometallic compounds is receiving increasing attention in the current literature, but as yet, little work has been reported on the photochemistry of metal-containing ketones. The objective of the work reported in this thesis was the synthesis of ligands for the formation of suitable metal-containing ketones. The initial studies were directed at the preparation of β- and ϒ-hydroxyketones by a variety of methods, but the major effort was later concentrated on the synthesis of phosphorus derivatives of o-hydroxyphenyl alkyl ketones . The reaction of o-hydroxyphenyl alkyl ketones with phosphorus trichloride afforded 2-chloro- 1,3,2-dioxaphosphorinans which were readily converted to the corresponding 2-alkoxy derivatives by reaction with various alcohols. Extension of the study to acteylacetone indicated that an analogous reaction occurs to give highly labile products. This part of the work has been accepted for publication in Chemical Communications. The reaction of o-hydroxyphenyl alkyl ketones with other phosphorus halides, such as dichlorophenyl phosphine and chlorodiphenylphosphine, has also been investigated. Reaction of the former reagent with o-hydroxyacetophenone gave a crystalline phosphorus-containing derivative; spectroscopic evidence indicates that this compound possesses an unusual structure and it is currently being studied by X-ray crystallography.
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    Syntheses related to some naturally occurring naphthopyranquinones
    (1986) Hugo, Victor Ignatius; Giles, R G F
    The naphtho[2,3-c]pyran ring system occurs not infrequently in Nature as derivatives of the 5,10-quinone. Examples include the eleutherins, the nanaomycins and the protoaphins some of which have been shown to possess antibiotic activity. The synthesis of these natural products requires appropriate regiospecific aromatic oxygenation of 2- acetylnaphthoquinone. Syntheses of 3-acetyl-5-methoxy-1, 4- naphthoquinone and the corresponding 5,7-dimethoxy analogue are described and the use of these in the syntheses of several naturally occurring pyranquinones or their derivatives, has been investigated. In the course of this work, an unusual Fries rearrangement and a novel baseinduced cyclisation were discovered - the latter affording several naphtho[2,3-c]pyrans in high yield. Previous routes to (±)-isoeleutherin and (±)-deoxyquinone A dimethyl ether have been recorded, but they give rise to a mixture of eleutherin and isoeleutherin in the first case, and a mixture of deoxyquinone A dimethyl ether and its cisdimethyl isomer. The synthetic routes to isoeleutherin and deoxyquinone A dimethyl ether developed during this investigation are highly stereoselective. The formation of the dimethyl ethers of quinones A and A', which is also highly stereoselective represents the first reported synthesis of the degradation products of the aphid pigments, protoaphin-fb and protoaphin-s1. The synthesis of 7-methoxyeleutherin is also described. The reaction of trifluoroacetic anhydride with various naphthalene derivatives is described and the potential of some of these acylated naphthalenes to be employed in the syntheses of naphtho[2, 3-c]pyrans and naturally occurring quinones has been investigated.
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    Synthesis and reactivity of some β-substituted alkylphosphonates
    (1986) Pearce, Madeleine Anne; Modro, Tomasz A
    The ability of the β-trimethylammonioethylphosphonic acid dianion to undergo fragmentation in alkaline conditions to produce trimethylamine, ethylene and metaphosphate was investigated. The results obtained were to give an indication of the susceptibility of (C₆H₃Cl₂)OCH₂CH₂N⁺R₂CH₂CH₂P(OR')O₂⁻ to analogous fragmentation to release 2-(3,4- dichlorophenoxy)ethyldialkylamine and ethylene, both well documented plant growth regulating hormones. Since the trimethylammonioethyl-substituted species was found to be stable to fragmentation, studies were embarked upon to convert this molecule into one which would react as required. The substitution of an alkyl group at the β-position of such a β-substituted alkyl phosphonate is reported to accelerate the rate of fragmentation. β-trimethylammoniopentylphosphonate was therefore expected to fragment where its ethyl analogue did not. Attempts at its synthesis were made by various approaches. 2- chloropentylphosphonic acid, a precursor, was successfully prepared and esterified (in order to protect the acid from premature fragmentation) so that it might be reacted with trimethylamine (a nucleophile), to produce diethyl β-trimethylammoniopentylphosphonate, which was then to be hydrolysed to the phosphonic acid form. Instead of the required substitution of Cl by Me₃N, the action of base on the ester produced diethyl 1-pentenylphosphonate. Only traces of the substitution product were observed. It was thought that the replacement of chlorine by a better leaving group such as bromine or iodine would favour the substitution product over the elimination product. Attempts at the synthesis of diethyl 2-iodopentylphosphonate and diethyl 2-bromopentylphosphonate by various means are described, but no satisfactory syntheses have been achieved, since once again the dehydrohalogenation product predominates. During an attempted synthesis of diethyl 2-iodopentylphosphonate by reaction of diethyl 2-chloropentylphosphonate with NaI, an unusual interaction between the sodium cation and the substrate in acetone solution was discovered. Evidence gleaned from ¹H, ¹³C and ³¹P nmr experiments points to the formation of a loose complex between the phosphonate part of the substrate and Na⁺. This phenomenon is also observed when other salts such as CaI₂, KSCN and NaClO₄ are present in solution.
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    Synthesis of delta-1(9)-octalinols and their analogues
    (1986) Lupuwana, Lincoln L; Elsworth, J F
    This project was initiated by the observation that a natural glyeoside of a triterpene, which incorporated the allylic alcoholic moiety 1 gave the novel ketone diene 2 when it was subjected to acetolysis. A number of octahydronaphthalinols (1, R=H) Δ 1 ( 9) octalinols), ' were prepared by reduction of the α, β unsaturated octalones obtained from cyclohexanones condensed with α, β -unsaturated ketones. These octalinols were characterised as their acetates (1, R=Ac). The attempts to convert these to the desired ketone dienes 2 by reaction with mixtures of acetic anhydride-acetic acid-boron trifluoride proved unsuccessful. Two model compounds derived from hecogenin and incorporating the octalinol residue 1 were also prepared in the hope that the analogous ketone 2 might be obtained. This reaction, too, was unsuccessful.
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    Synthesis of naphtho{2,3-c}pyrans including the aphin-derived quinone A'
    (1987) Ramdohr, Jurgen Ernst; Green, Ivan Robert; Yorke, Selwyn
    Chapter One describes the synthesis of a trifluoroethylnaphtho-1, 4-quinone via a regiospecific trifluoroacetylation of an appropriately substituted naphthalene. Chapter Two describes the synthesis of the methyl ethers of the naturally occurring quinones A and deoxyquinone A for evaluation of their "anti-cancer" activity by the National Institutes of Health. In Chapter Three the final few steps of the synthesis of the aphid-derived quinone A' are described. This was made possible by the development of an efficient route for the conversion of a precursor to quinone A' via the corresponding chloro-derivative.
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    The synthesis of some naphthol (2,3-c) pyrans
    (1981) Chorn, Trevor Anthony; Giles, Robin G F; Mitchell, P R K
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    Tertiary N-acyl phosphoramidates : a mechanistic study of their formation and collapse in reactions with nucleophiles
    (1983) Hendrickse, Theodore Franklin; Modro, Tomasz A
    Different synthetic approaches to tertiary mixed phosphoric-carboxylic imides(III) are discussed. The preparation of (III) via the N-acylation of phosphoramidates was investigated. The reaction of PhC(O)X (X = Br, Cl, F) with the conjugate base of (EtO)₂P(O)NHMe (IX) yields three products: PhCO₂Et (4), PhC(O)NHMe (5) and (PhCO)₂NMe (6). (5) and (6) are formed via the initial rapid formation of (EtO)₂P(O)-NMe-C(O)Ph (IIIe), while (4) results from the E1cB related reaction of (EtO)₂P(O)NMe involving electrophilic assistance by PhC(O)X. The attack of various nucleophilic species at the mixed-imide (IIIe) was studied, and the possible mechanisms of the P-N bond cleavage, followed by the N-methyl transfer from the phosphoryl to the carbonyl centre are discussed.