279 results for Brimble, Margaret

  • 1H and 13C NMR spectra of C-6 and C-9 substituted 3-azabicyclco[3.3.1]nonanes

    Goodall, Kirsten; Brimble, Margaret; Barker, David (2008)

    Journal article
    The University of Auckland Library

    The 1H and 13C NMR data for 3-azabicyclo[3.3.1]nonanes with OH and OMe substituents at C-6 and C-9 were measured using 1D (DEPT) and 2D (COSY, HSQC, HMBC, NOESY) experiments. Comparison of this NMR data illustrates the effects of stereochemistry and substitution at these positions.

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  • Methyltrichlorosilane, CAS No: 75-79-6 Update

    Brimble, Margaret (2010)

    Book item
    The University of Auckland Library

    InChI = 1S/CH3Cl3Si/c1-5(2,3)4/h1H3 InChIKey = JLUFWMXJHAVVNN-UHFFFAOYSA-N (precursor to organosilicon compounds;1 silylating agent;1 Lewis acid2) Physical Data: bp 66 °C; d 1.273 g cm–3. Solubility: sol methylene chloride. Form Supplied in: liquid; commercially available. Purification: can be purified by distillation. Handling, Storage, and Precautions: is corrosive and moisture sensitive. It should be handled in an anhydrous atmosphere in a fume hood.

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  • Crystal Structures of (3S*, 4S*, 5S*, 6S*)-3,4-Epoxy-1,7-dioxaspiro[5.5]undecan-5-ol, (3R*, 5S*, 6S*)-1,7-Dioxaspiro[5.5]undec-3,5-diyl diacetate and (4S*, 5S*, 6S*)-1,7-Dioxaspiro[5.5]undecan-4,5-diol

    Brimble, Margaret; Johnston, AD; Hambley, TW; Turner, P (1997)

    Journal article
    The University of Auckland Library

    The structures of (3S*,4S*,5S*,6S*)-3,4-epoxy-1,7-dioxaspiro[5.5]undecan-5-ol (2), (3R*,5S*,6S*)-1,7- dioxaspiro[5.5]undecane-3,5-diyl diacetate (4) and (4S*,5S*,6S*)-1,7-dioxaspiro[5.5]undecane-4,5-diol (5) have been determined by X-ray crystallography. The unsubstituted tetrahydropyran ring in (2) adopts an axial position with respect to the epoxy-substituted ring and the hydroxy group at C5 is syn to the epoxide group. Intermolecular hydrogen bonding is observed between the C5 hydroxy group and O1. The two six-membered rings in (4) adopt chair conformations and the two acetate groups adopt 1,3-diaxial positions. The C5 hydroxy group in (5) assumes an axial position anti to the C-O bond of the neighbouring ring whilst 4-OH occupies an equatorial position. Intermolecular hydrogen bonding is also observed between 4-OH and 5-OH. Compound (2), C9H14O4, M 186·21, crystallized in the monoclinic space group P 21/c with a 7·867(1), b 12·2060(9), c 9·3676(8) Å, b 102·744(8), V 877·4(1) Å 3 and No 1163 [I > 2·5s (I)], R 0·031, Rw 0·035. Compound (4), C13H20O6, M 272·30, crystallized in the triclinic space group P 1 with a 9·902(1), b 11·0024(9), c 6·9183(5)Å, a 104·078(8), b 96·769(9), g 101·980(8), V 703·8(1) Å 3 , No 1657 [I > 2·5s(I)], R 0·047, Rw 0·044. Compound (5), C9H16O4, M 188·22, crystallized in the orthorhombic space group Pbca with a 25·504(3), b 8·909(2), c 8·038(2) Å, V 1826·4(5) QA 3 , No 1096 [I > 2·5s(I)], R 0·030, Rw 0·030.

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  • Recent Developments in Neoglycopeptide Synthesis

    Brimble, Margaret; Miller, N; Williams, GM (2011-04)

    Book item
    The University of Auckland Library

    Closing a gap in the literature, this is the only book series in 6 volumes to cover this important topic in organic and biochemistry.

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  • Stereoselective Synthesis of 4-Substituted 4-Hydroxypiperidines via Epoxidation-Ring Opening of 4-Methylenepiperidines

    Mckay, VA; Thompson, SJ; Tran, PM; Goodall, KJ; Brimble, Margaret; Barker, David (2010)

    Journal article
    The University of Auckland Library

    Reaction of 9-methylene-3-azabicyclo[3.3.1]nonanes with trifluoroperacetic acid results in stereoselective epoxidation to give the syn-epoxide. Intermolecular hydrogen bonding between the protonated tertiary amine and the peracid is responsible for the high levels of stereoselectivity.

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  • Peripheral administration of a novel diketopiperazine, NNZ 2591, prevents brain injury and improves somamtosensory-motor function following hypoxia-ischemia in adult rats.

    Guan, Jian; Mathai, Sam; Harris, Paul; Wen, Jingyuan; Zhang, J; Brimble, Margaret; Gluckman, Peter (2007)

    Journal article
    The University of Auckland Library

    The current study describes the neuroprotective effects of an endogenous diketopiperazine, cyclo-glycyl-proline (cyclic GP), in rats with hypoxic-ischemic brain injury and the pre-clinical development of an analogue, cyclo-L-glycyl-L-2-allylproline (NNZ 2591), modified for improved bioavailability. The compounds were given either intracerebroventricularly or subcutaneously 2h after hypoxia-ischemia. Histology, immunohistochemistry and behavior were used to evaluate treatment effects. The central uptake of NNZ 2591 was also examined in normal and hypoxic-ischemic injured rats by HPLC-mass spectrometry. Central administration of cyclic GP or NNZ 2591 reduced the extent of brain damage in the lateral cortex, the hippocampus and the striatum (p<0.0001). NNZ 2591 treatment not only reduced both caspase-3 mediated apoptosis and microglial activation but also enhanced astrocytic reactivity, which may mediate its protective effect. The pharmacokinetic profile and potent long-term protective effects of NNZ 2591 suggests its utility for the treatment of ischemic brain injury and other neurological conditions requiring chronic intervention.

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  • Enantioselective synthesis of pyranonaphthoquinone antibiotics using a CBS reduction/cross-metathesis/oxa-Michael strategy.

    Hume, Paul; Sperry, Jonathan; Brimble, Margaret (2011)

    Journal article
    The University of Auckland Library

    The enantioselective syntheses of deoxydihydrokalafungin (5), cis-deoxydihydrokalafungin (6) and deoxykalafungin (7) are reported. The strategy was based on 4 key reactions: (1) CBS reduction of prochiral ketone 10 to introduce chirality at C-1, (2) radical allylation of quinone 9a, (3) cross-metathesis of dimethoxynaphthalene 13 with methyl acrylate, and (4) intramolecular oxa-Michael addition of alcohol 8 to form the core naphthopyran ring system. This novel approach delivers naphthopyrans possessing the natural trans-stereochemistry observed in the pyranonaphthoquinone family of antibiotics.

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  • Heteroatom-directed reverse Wacker oxidations. Synthesis of the reported structure of (-)-herbaric acid.

    Choi, Peter; Sperry, Jonathan; Brimble, Margaret (2010)

    Journal article
    The University of Auckland Library

    A microwave-assisted chemoenzymatic resolution has been used to install the C3 stereocenter of the reported structure of the fungal metabolite herbaric acid in high enantiomeric excess. The synthesis and stereochemical assignment was accomplished using a completely regioselective anti-Markovnikov addition of water to vinylphthalide 3, achieved using a heteroatom-directed Wacker oxidation that proceeds with retention of stereochemistry. These results establish that so-called "reverse" Wacker oxidations are a viable alternative to hydroboration/oxidation procedures.

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  • [4R*,5R*,6S*]-1,7-dioxaspiro[5.5]undecane-4,5-diol

    Brimble, Margaret; Johnston, AD (1997-01-01)

    Journal article
    The University of Auckland Library

    A solution of [3R*,4R*,5S*,6S*]-3,4-epoxy-1,7-dioxaspiro[5.5]undecan-5-ol (1) (561 mg, 3.01mmol) in dry tetrahydrofuran (30 ml) under a nitrogen atmosphere was cooled to 0 deg.C in an ice/water bath. Lithium aluminium hydride (4.52 ml, of a 1 mol L-1 solution in THF, 4.52 mmol) was added in 3 portions over 1 minute, and the reaction mixture allowed to stir at 0 deg.C for 1 h then room temperature for 12 h....

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  • Synthesis of Neoglycopeptides via Click Chemistry

    Miller, N; Williams, Geoffrey; Brimble, Margaret (2010)

    Journal article
    The University of Auckland Library

    Novel chemical methods to access homogeneous samples of glycopeptides and glycoproteins and their mimetics, so-called neoglycopeptides and neoglycoproteins, have developed rapidly in recent years owing to an increased need to investigate both their roles in molecular biology and their potential as therapeutic agents. This article summarizes the application of the copper-catalyzed azide-alkyne cycloaddition for the chemical synthesis of neoglycopeptides and neoglycoproteins.

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  • [3S*,5S*,6S*]-1,7-dioxaspiro[5.5]undecane-3,5-diyl diacetate

    Brimble, Margaret; Johnston, AD (1997-01-01)

    Journal article
    The University of Auckland Library

    To a solution of [3S*,5S*,6S*]-1,7-dioxaspiro[5.5]undecane-3,5-diol (1) [1] (33 mg, 0.17 mmol) in dichloromethane (10 ml) was added triethylamine (54 mg, 0.53 mmol), acetic anhydride (34 mg, 0.34 mmol) and 4-dimethylaminopyridine (3 mg). The reaction mixture allowed to stand at room temperature for 1 h, then quenched with water (2.0 ml), extracted with dichloromethane (2x 50 ml) and dried over sodium sulphate. ...

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  • Synthesis of triazole analogues of the nanaomycin antibiotics using 'click chemistry'

    Rathwell, K; Sperry, Jonathan; Brimble, Margaret (2010)

    Journal article
    The University of Auckland Library

    A series of triazole analogues of the nanaomycin family of antibiotics have been prepared using a 'click' dipolar cycloaddition of a naphthalene azide to various alkynes, followed by oxidation to the desired pyranonaphthoquinones. (C) 2010 Elsevier Ltd. All rights reserved.

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  • (±)-1-{8'-(tert-Butyldiphenylsilyloxymethyl)-1',7'-dioxaspiro[5.5]undecan-2'-yl}uridine

    Choi, Ka; Brimble, Margaret; Groutso, Tatiana (2008)

    Journal article
    The University of Auckland Library

    The crystal structure of the title compound, C30H38N2O5Si, has been investigated to establish the relative stereochemistry at the spiro ring junction and the two anomeric centres. Each of the O atoms in the tetrahydropyran rings adopts an axial position on the neighbouring ring. This bis-diaxial conformation is adopted, thus gaining maximum stablization from the anomeric effect. The silyl-protected hydroxymethyl and uracil substituents adopt equatorial positions on their associated tetrahydropyran rings, thereby minimizing unfavourable steric interactions. The dimeric (2'R*,6'R*,8'R*)- and (2'S*,6'S*,8'S*)-uridine units are connected to each other across crystallographic inversion centres via intermolecular N-HO hydrogen bonds.

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  • (2 '' S,5 '' R,7 '' S)-2-[2 '-(2 ''-Methyl-1 '',6 ''-dioxaspiro-[4.5]dec-7 ''-yl)ethylsulfonyl]-1,3-benzothiazole

    Clark, George; Robinson, JE; Brimble, Margaret (2006)

    Journal article
    The University of Auckland Library

    The crystal structure of the title compound, C18H23NO4S2, has been investigated in order to establish the relative stereochemistry at the spiro ring junction and the absolute stereochemistry of the molecule. The title compound is a key intermediate for the synthesis of the spiroacetal-containing anti-Helicobacter pylori agent, spirolaxine methyl ether, for which the absolute stereochemistry has not previously been reported.

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  • Allylic functionalization of the 1,7-dioxaspiro[5.5]-undec-4-ene and 1,6,8-trioxadispiro[4.1.5.3]-pentadec-13-ene ring systems

    Brimble, Margaret; Edmonds, MK; Williams, GM (1992)

    Journal article
    The University of Auckland Library

    Allylic bromination of the bicyclic spiroacetals 5, 6 and 7 gave predominantly the axial bromides 15, 21 and 23 which underwent SN2 displacement to the equatorial alcohols 17, 22 and 25 respectively, using potassium superoxide and 18-crown-6 in THF/DMSO (10:1). Allylic bromination of the cis-bis-spiroacetal 26 gave predominantly the rearranged allylic bromide 29 which afforded alcohols 30 and 31 resulting from both SN2′ and SN2 displacement upon treatment with potassium superoxide. Bromination of the trans-bis-spiroacetal 27 afforded a complex mixture from which only the non-rearranged bromide 34 could be isolated. This bromide 34 afforded the axial alcohol 37 upon treatment with potassium superoxide.

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  • Approaches to the D-E ring of the polyether antibiotic salinomycin using sharpless asymmetric dihydroxylation

    Brimble, Margaret; Prabaharan, H (1998)

    Journal article
    The University of Auckland Library

    The work described herein provides a model system for appendage of the E ring of epi-17-deoxy-(O-8)-salinomycin3 onto bis-spiroacetal aldehyde 6. The conversion of aldehyde 7 to bicyclic ether 8via silver assisted ring expansion of the mesylate derived from tetrahydrofuran alcohol 33 is described. Attempts to provide a stereoselective synthesis of epoxide 27 required for the preparation of 33 and hence 8 are reported. Alcohol 9 was prepared by chelation controlled addition of the Grignard reagent derived from bromide 15 to aldehyde 7. Bromide 15 in turn was prepared as a 9:1 E:Z mixture of isomers with the required E-stereochemistry being introduced via a stereoselective Julia ring opening of cyclopropane 20. Sharpless asymmetric dihydroxylation of alkenes 10 and 11 readily provided diols 22 and 25 [or 23 and 26 respectively], however, their subsequent conversion to epoxides 27 and 30 with retention of stereochemistry proved unsuccessful. Cyclic sulfites 37, 39 and sulfates 42, 45 were investigated as epoxide equivalents. Base induced cyclization of sulfites 37, 39 only afforded triols 21, 24. Analogous reaction using sulfates 42, 45 favoured endo cyclization to a tetrahydropyran ring, however, the acidic conditions required for hydrolysis of the initial alkyl sulfate effected undesired elimination of the resultant tertiary alcohol. Whilst a stereoselective synthesis of the correct epoxide 27 required for preparation of tetrahydropyran 8via ring expansion of tetrahydrofuran 33 has not been achieved, these latter conversions have been successfully demonstrated by the conversion of epoxides 28 and 31 to a 1:1 mixture of tetrahydrofurans 33 and 34 which were separable by flash chromatography. Subsequent ring expansion of these tetrahydrofurans 33 and 34 to tetrahydropyrans 8 and 14 was effected upon treatment with methanesulfonyl chloride followed by silver carbonate.

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  • Assessing the Molecular Basis for Rat-Selective Induction of the Mitochondrial Permeability Transition by Norbormide

    Zulian, A; Petronilli, V; Bova, S; Dabbeni-Sala, F; Cargnelli, G; Cavalli, M; Rennison, David; Stäb, J; Laita, Olivia; Lee, Danny; Brimble, Margaret; Hopkins, Brian; Bernardi, P; Ricchelli, F (2007)

    Journal article
    The University of Auckland Library

    It was recently demonstrated that the rat-selective toxicant norbormide also induces rat-selective opening of the permeability transition pore (PTP) in isolated mitochondria. Norbormide is a mixture of endo and exo stereoisomers; however, only the endo forms are lethal to rats. In the present study we tested both endo and exo isomers as well as neutral and cationic derivatives of norbormide to: (i) verify if the PTP-regulatory activity by norbormide is stereospecific; (ii) define the structural features of norbormide responsible for PTP-activation, (iii) elucidate the basis for the drug species-specificity. Our results show that: (i) norbormide isomers affect PTP in a rat-selective fashion; however, no relevant differences between lethal and non-lethal forms are observed suggesting that drug regulation of PTP-activity and lethality in rats are unrelated phenomena; (ii) a (phenylvinyl)pyridine moiety represents the key element conferring the PTP-activating effect; (iii) cationic derivatives of rat-active compounds accumulate in the matrix via the membrane potential and activate the PTP also in mouse and guinea pig mitochondria. These findings suggest that the norbormide-sensitive PTP-target is present in all species examined, and is presumably located on the matrix side. The species-selectivity may depend on the unique properties of a transport system allowing drug internalisation in rat mitochondria.

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  • DIRECTED ORTHO METALATIONS OF TERTIARY BENZAMIDES USING LACTONES AS ELECTROPHILES

    BRENSTRUM, TJ; Brimble, Margaret; Stevenson, Ralph (1994-04-18)

    Journal article
    The University of Auckland Library

    The efficient and regiospecific synthesis of polysubstituted aromatic compounds has been aided significantly by the advances made in the use of directed ortho metalation reactions. This approach involves deprotonation of a site ortho to a heteroatom-containing directed metalating group (DMG) by a strong base, normally an alkyllithium reagent, leading to an ortho-lithiated species which upon treatment with electrophilic reagents yield 1,2-disubstituted products.(1) The addition of a range of carbon electrophiles has been investigated including ketones, aldehydes, acyl halides and alkyl halides, carbamoyl chlorides, carbon dioxide and dimethyl formamide. Ester and lactone electrophiles have been less widely used.(1) In the latter case only a few examples have been reported using lactones derived from a carbohydrate with the use of an ether as the directed metalating group.(2,3)

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  • NNZ-2566: A Gly-Pro-Glu Analogue With Neuroprotective Efficacy in a Rat Model of Acute Focal Stroke

    Bickerdike, MJ; Thomas, GB; Batchelor, DC; Sirmianne, ES; Leong, W; Lin, H; Sieg, Frank; Wen, Jingyuan; Brimble, Margaret; Harris, Paul; Gluckman, Peter (2009)

    Journal article
    The University of Auckland Library

    The N-terminal cleavage product of human insulin-like growth factor-1 (IGF-1) in the brain is the tripeptide molecule Glypromate® (Gly–Pro–Glu). Glypromate® has demonstrated neuroprotective effects in numerous in vitro and in vivo models of brain injury and is in clinical trials for the prevention of cognitive impairment following cardiac surgery. NNZ-2566 is a structural analogue of Glypromate®, resulting from α-methylation of the proline moiety, which has improved the elimination half-life and oral bioavailability over the parent peptide. In vivo, NNZ-2566 reduces injury size in rats subjected to focal stroke. An intravenous infusion of NNZ-2566 of 4 h duration (3–10 mg/kg/h), initiated 3 h after endothelin-induced middle-cerebral artery constriction, significantly reduced infarct area as assessed on day 5. Neuroprotective efficacy in the MCAO model was also observed following oral administration of the drug (30–60 mg/kg), when formulated as a microemulsion. In vitro, NNZ-2566 significantly attenuates apoptotic cell death in primary striatal cultures, suggesting attenuation of apoptosis is one mechanism of action underlying its neuroprotective effects. NNZ-2566 is currently in clinical trials for the treatment of cognitive deficits following traumatic brain injury, and these data further support the development of the drug as a neuroprotective agent for acute brain injury.

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  • Pyranonaphthoquinones - isolation, biological activity and synthesis

    Sperry, Jonathan; Bachu, P; Brimble, Margaret (2008)

    Journal article
    The University of Auckland Library

    A review of the isolation, biological activity and synthesis of pyranonaphthoquinones and closely related compounds is provided.

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