283 results for Brimble, Margaret

  • Professor Jim Coxon. A Tribute

    Brimble, Margaret; Steel, P (2006)

    Journal article
    The University of Auckland Library

    This special issue of the ARKIVOC is dedicated to Professor Jim Coxon to mark his 65 th birthday and acknowledge his contribution to New Zealand science through his diverse achievements in mechanistic organic chemistry carried out at the University of Canterbury.

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  • Equipment Access for Graduate Students - The First Hurdle

    Brimble, Margaret (2007)

    Journal article
    The University of Auckland Library

    Last month, Academy Councillor Carolyn Burns reflected on the unwieldy systems of compliance and accountability that our researchers face. These systems affect our opportunities to conduct cutting edge science in New Zealand, to attract excellent scientists from overseas, and to retain some of our best research scientists here. ...

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  • Di-(-)-(1R,2S)-2-phenyl-1-cyclohexyl Diazenedicarboxylate

    Brimble, Margaret (2002)

    Book item
    The University of Auckland Library

    InChI = 1S/C26H30N2O4/c29-25(31-23-17-9-7-15-21(23)19-11-3-1-4-12-19)27-28-26(30)32-24-18-10-8-16-22(24)20-13-5-2-6-14-20/h1-6,11-14,21-24H,7-10,15-18H2/b28-27+/t21-,22-,23+,24+/m0/s1 InChIKey = RHBWBKFUCXVAMA-KQEKZTIUSA-N (reagent used as a chiral azo-enophile in asymmetric azo-ene reactions) Alternate Name: (1R-{1α[E(1R*,2S*)],2β})-Bis(2-phenylcyclohexyl) diazenedicarboxylate. Physical Data: [α]D –56.9 (c 0.65, CHCl3). Solubility: soluble in CH2Cl2, diethyl ether, and most organic solvents. Form Supplied in: yellow oil. Analysis of Reagent Purity: 1H NMR, IR, TLC, elemental analysis. Preparative Methods: The title reagent is prepared1 by reaction of (1R, 2S)-2-phenyl-1-cyclohexanol with excess phosgene in the presence of quinoline to afford a chloroformate which is treated directly with hydrazine monohydrate (0.5 equiv) to afford di-(–)-(1R, 2S)-2-phenyl-1-cyclohexyl diazanedicarboxylate. Oxidation of the diazanedicarboxylate to the diazenedicarboxylate is then readily effected using N-bromosuccinimide and pyridine (eq 1).

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  • 2-Trimethylsilyloxyfuran, CAS No: 61550-02- Update

    Brimble, Margaret; Sperry, Jonathan (2008)

    Book item
    The University of Auckland Library

    InChI = 1S/C7H12O2Si/c1-10(2,3)9-7-5-4-6-8-7/h4-6H,1-3H3 InChIKey = ILBCDLOQMRDXLN-UHFFFAOYSA-N (provides 5-substituted 2(5H)-furanones by alkylation,2 aldolization,3 and conjugate addition;4 transforms quinones into furo[3,2-b]benzofurans;5 useful for the four-carbon elongation of sugars6) Alternate Name: TMSOF. Physical Data: bp 44–46 °C/17 mmHg; d 0.93 g mL–1. Solubility: sol most organic solvents, e.g. CH2Cl2, Et2O, benzene, THF, MeCN. Form Supplied in: colorless liquid; commercially available (98% pure) but expensive. Preparative Method: accessible by silylation of 2(5H)-furanone,1c,5b which is obtained at very low cost by oxidation of furfural (see also ). Handling, Storage, and Precautions: flammable liquid; sensitive to moisture. To avoid hydrolysis, it should be kept under Ar at –18 °C or below. For best results, reactions should be performed under strictly anhydrous conditions in aprotic solvents. Use in a fume hood.

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  • Polyether Antibiotics

    Brimble, Margaret (2006)

    Book item
    The University of Auckland Library

    Several polyether antibiotics have found commercial application as anticoccidials in poultry farming and in improvement of feed efficiency for ruminants. These antibiotics are characterized by multiple tetrahydrofuran and tetrahydropyran rings connected by aliphatic bridges, direct CC linkages, or spiro linkages. Other features include a free carboxyl function, many lower alkyl groups, and a variety of functional oxygen groups. These structural features enable transport of cations across lipid membranes. Some polyethers have found application as components in ion-selective electrodes for use in clinical medicine or in laboratory studies involving transport studies or measurement of transmembrane electrical potential. The polyether class can be subdivided based on the number of carbon atoms in the backbone, ie, the longest chain of contiguous carbons between the carboxyl group and the terminal carbon. The 30 C skeleton group accounts for ~60% of the polyethers for which structures have been determined. Monensin, widely used as an anticoccidial and feed efficiency enhancer, is an example of the 26 C backbone class. Maduramicin, another commercially important polyether, is shown as an example of the 30 C group with a sugar moiety. Many of the production procedures for polyethers utilize the separation of the mycelium followed by extraction using solvents such as methanol or acetone. A number of the polyethers can be readily crystallized. Polyethers such as monensin, lasalocid, salinomycin, and narasin are sold in many countries in crystalline or highly purified forms for incorporation into feeds or sustained-release bolus devices. There are also mycelial or biomass products, especially in the United States, generally prepared by separation of the mycelium and then drying by azeotropic evaporation, fluid-bed driers, or other types of commercial driers. Sophisticated methods have been developed for the chemical analysis of polyether antibiotics in feeds and residues that include the use of liquid chromatography–mass spectrometry (LCMS), bioautography, and enzyme-linked immunosorbent assay (ELISA). The polyether antibiotics exhibit a broad range of biological, antibacterial, antifungal, antiviral, anticoccidial, antiparasitic, and insecticidal activities. They improve feed efficiency and growth performance in ruminant and monogastric animals. Only the anticoccidial activity in poultry and cattle, and the effect on feed efficiency in ruminants such as cattle and sheep, are of commercial interest. It is estimated that the polyether ionophores constitute > 80% of the total worldwide usage of anticoccidials. Bacteria belonging to the order Actinomycetales are the organisms reported to produce all of the polyethers. Most are secondary metabolites of Streptomyces sp. with the species hygroscopicus and albus accounting for about one-third of the antibiotics. An alternative to the Cane-Clemer-Westley unified stereochemical model for the biosynthesis of polyether antibiotics via cyclization of polyepoxides has been proposed. The alternative model invokes construction of polyethers via hydroxyl-directed syn oxidative polycyclization of a hydroxypolyene. Biosynthesis of polyether antibiotics is catalyzed by a large family of polyketide synthases (PKSs) that function in a similar manner to fatty acid synthase using malonyl-CoA, methylmalonyl-CoA, and ethylmalonyl-CoA as extender units for building the polyketide backbone. Many gene clusters encoding the enzymes of polyketide biosynthesis have been cloned and characterized. Combinatorial biosynthesis provides a promising new approach of growing importance for the synthesis of hybrid “unnatural” antibotics by means of genetic engineering of recombinant strains bearing the biosynthetic genes of bacterial polyketide synthases. The polyether antibiotics provide a complex molecular framework for the development of new synthetic strategies for their total synthesis. Over 16 of the polyether antibiotics have succumbed to total synthesis. Monensin and salinomycin represent ~ 65–70% of worldwide usage of polyether antibiotics for controlling coccidiosis. Lasalocid, narasin, and maduramicin make up the remainder. Other compounds for coccidiosis control include nicarbazine, halofunginone, amprolium, and robenidine.

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  • Instant Insight: Life at the Extremes

    Wilson, Zoe; Brimble, Margaret (2008)

    Journal article
    The University of Auckland Library

    There are minimature natural product libraries to be found in the most unexpected places. Zoe Wilson and Margaret Brimble of the University of Auckland, New Zealand, delve deeper.

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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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  • Alkylarsenic, -Antimony, and -Bismuth Compounds volume 2 Chapter 2.09

    Brimble, Margaret; Levi, MS (2005)

    Book item
    The University of Auckland Library

    The chemistry of arsenic, antimony and bismuth, a class of elements in group V of the periodic table and known as the pnicogens, has a colorful past from the ancient alchemists to Cadet’s fuming arsenical liquid to green pigments. Today, they are even used in some lasers. This chapter presents an update of the preparations of compounds containing one or more of the pnicogens as well as complexes with other metals.

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  • A Facile Synthesis of Spiroketals

    Brimble, Margaret; Officer, DL; Williams, GM (1988)

    Journal article
    The University of Auckland Library

    A convenient synthetic approach to spiroketals based on the addition of α-sulfonylcarbanions to lactones is described.

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  • Synthesis of a Functionalized Bis-Spiroacetal

    Brimble, Margaret; Williams, GM; Baker, R; James, M (1990)

    Journal article
    The University of Auckland Library

    The synthesis of bis-spiroacetal (15) bearing an hydroxymethyl group at C-2 is described establishing a methodology for preparation of the polyether antibiotics salinomycin and narasin. Formation of an important iodohydrin intermediate has been accomplished by a highly efficient reaction of an epoxide with LiI catalysed by BF3.Et2O in THF. Displacement of the resulting neopentyl iodide was achieved in high yield by reaction of the iodide with potassium superoxide in dimethylsulphoxide/tetrahydrofuran in the presence of 18-crown-6. The synthesis of bis-spiroacetal (15) has been achieved the following sequence.

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  • SYNTHESIS OF BICYCLIC PYRAZINONES VIA ADDITION OF HETEROCYCLIC AMINES TO A NITRO-ALKENE

    Brimble, Margaret; Johnson, AD (1994)

    Journal article
    The University of Auckland Library

    Michael addition of heterocyclic amines (6), (10), (13) and (17) to nitro-olefin (3) followed by reduction/cyclization of the nitro group of the adduct provides a convenient synthesis of the bicyclic pyrazinones (8), (12), (16), (19) and (20) which are found in several natural products. Michael addition of heterocyclic amines to a nitro-alkene followed by reduction/cyclization of the nitro group of the adduct provides a convenient synthesis of bicyclic pyrazinones found in several natural products.

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  • A Convergent Synthesis of the [4.4]-Spiroacetal-gamma-lactones Cephalosporolides E and F

    Brimble, Margaret; Finch, OC; Heapy, AM; Fraser, JD; Furkert, DP; O'Connor, PD (2011)

    Journal article
    The University of Auckland Library

    A short convergent synthesis of the fungal metabolites cephalosporolides E and F is reported. The key step makes use of a chelation-controlled Mukaiyam

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  • Synthesis of the Bis-Spiroacetal Moiety of 17-epi-20-Deoxysalinomycin

    Brimble, Margaret; Williams, GM (1992)

    Journal article
    The University of Auckland Library

    The synthesis of the bis-spiroacetal moiety of 17-epi-20-deoxysalinomycin (4) is reported in which the key step involves oxidative cyclization of the hydroxy spiroacetals 14 and 15 to the bis-spiroacetals 16 and 17 using (diacetoxyiodo)benzene and iodine under photolytic conditions.

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  • Synthesis of Tricyclic Aryl Spiroacetals Related to the Papulacandins

    Brimble, Margaret; Robertson, SG (1996)

    Journal article
    The University of Auckland Library

    A convenient synthesis of aryl spiroacetals related to the antifungal agents, the papulacandins, is reported. The synthetic methodology involves the addition of ortho-lithiated diethylbenzamides to lactones followed by acid catalysed cyclization of the resultant keto-alcohols. A series of aromatic spiroacetals is synthesized via the reaction of ortho-lithiated amides with lactones followed by cyclization of the resultant keto-alcohols with p-TSA.

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  • Toward the Total Chemical Synthesis of the Cancer Protein NY-ESO-1

    Brimble, Margaret; Harris, PWR (2010)

    Journal article
    The University of Auckland Library

    During the course of developing a synthetic route for the cancer protein NY-ESO-1 using native chemical ligation, a number of the required thioester polypeptide fragments were unable to be synthesized effectively using Boc solid phase peptide synthesis. Modification of the SPPS protocols to include an arginine tag at the C terminus linked via the thioester resulted in a better purity profile and enhanced solubility, facilitating purification by HPLC. During preparation of another reactive partner for ligation that contained an internal Cys(Acm) residue by Fmoc SPPS, extensive loss of the Acm group occurred during cleavage from the resin while substitution with Cys(tBu) resulted in no loss of protecting group. It was shown that native chemical ligation of N-terminal cysteine peptide 155–180 containing the Cys(tBu) residue with thioester 140–154 was slow, incomplete and led to extensive HPLC column fouling. Subsequent incorporation of a C-terminal arginine tag into the N-terminal NY-ESO-1 155-180 fragment joined by a base labile 4-hydroxymethylbenzoic acid (HMBA) linker facilitated rapid quantitative ligation. The HMBA linker was demonstrated to be stable to the conditions required for native chemical ligation, subsequent transformations and final purification. Importantly it was effectively removed at pH = 10.

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  • Review of book Science of Synthesis, Volume 28: Compounds with Two Carbon-Heteroatom Bonds: Quinones and Heteroatom Analogues, by A. G. Griesbeck

    Brimble, Margaret (2007)

    Unclassified
    The University of Auckland Library

    Volume 28, Quinones and Heteroatom Analogues comprises part of the highly esteemed reference work Science of Synthesis, Houben–Weyl Methods of Molecular Transformations that consists of 48 planned volumes and is already an essential tool for modern retrieval of reliable synthetic information. Volume 28 covers modern synthetic methods to prepare quinones and their heteroatom analogues, and is one of nine volumes comprising Category 4 (Compounds with Two Carbon–Heteroatom Bonds). ...

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  • Chemistry Research: Making Molecules for Medicines

    Brimble, Margaret (2008)

    Book item
    The University of Auckland Library

    Natrual products have long been regarded as 'nature's medicine chest' because they offer a rich source of compounds with complex and novel structures tha inspire the development of new drugs. The synthesis of these challenging, naturally occurring compunds in the laboratory is a scientific endeauvour that forms the backbone of the pharmaceutical industry. ...

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  • REARRANGEMENT OF A FURO[3,2-B]NAPHTHO[2,1-D]FURAN TO A PYRANONAPHTHOQUINONE

    Brimble, Margaret; HODGES, R; STUART, SJ (1988-01-01)

    Journal article
    The University of Auckland Library

    The ceric ammonium nitrate oxidation of the furo(3,2-b]naphtho[2,l-d]furan-8(9H)- ones (5c,5d) gave the rearranged hemiketals (llc,lld) in 72-76% yield. -- Reduction of the hemiketals (llc,lld) provided an entry to a pyranonaphthoquinone with a fused Y-lactone as -- present in the pyranonaphthoquinone antibiotics kalafungin (5) and nanaomycin D (I).

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  • Investigation into the racemic X-ray structure of the antimicrobial protein snakin-1

    Yeung, Ho; Yosaatmadja, Yuliana; Squire, Christopher; Harris, Paul; Baker, Edward; Brimble, Margaret (2015-08-31)

    Conference poster
    The University of Auckland Library

    Snakin-1 is a 63 residue antimicrobial protein originally isolated from potato (Solanum tuberosum).1 It is active against a number of bacterial and fungal phytopathogens such as Clavibacter michiganensis, Pseudomonas syringae and Fusarium solani. Snakin-1 is a member of the GASA (gibberellic acid stimulated in Arabidopsis)/snakin family and the mature protein consists of a GASA domain incorporating six intramolecular disulfide bonds.2 The amino acid sequences of these proteins do not correspond to any known structural motifs. GASA/snakin proteins are found in a variety of plant species and appear to be involved in a range of functions including cell elongation and cell division.2 Their expression profiles support these roles and are commonly linked to development.2 It has also been speculated that the 12 conserved cysteines in these proteins perform a role in redox regulation.2 We have recently completed the total chemical synthesis of native Snakin-1 and showed that its antimicrobial activity is comparable to that of the naturally occurring protein.3 In an attempt to understand how this small protein functions we have determined its threedimensional structure by X-ray crystallography using a quasi-racemic protein system.4 Phase information for structural determination was obtained by radiation-damage induced phasing.5 The structure of snakin-1 appears to be novel, different to known classes of cysteine-rich plant antimicrobial peptide. Its features include a large and distinctly electropositive loop that we speculate to be membrane targeting, and a two helix bundle which is a potential membrane-interacting feature able to disrupt the structural integrity of its target bacteria.

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  • Targeting synthetic glycopeptides to MGL on Dermal Dendritic cells

    McIntosh, Julie; Angel, CE; Chen, CJJ; Manning, K; Mansell, Claudia; Agrawai, S; Harris, Paul; Williams, Geoffrey; Squire, Christopher; Brimble, Margaret; Dunbar, Peter (2011-02-14)

    Conference poster
    The University of Auckland Library

    The ability of a peptide vaccine to stimulate T cells in vivo might be improved by specifically targeting the peptide to dendritic cells (DC). The C-type lectin Macrophage Galactose-type lectin, MGL (CD301), has been shown to bind to N-acetyl-galactosamine (GalNAc) and small peptides bearing O-linked GalNAc. Synthetic GalNAc can be produced using relatively simple organic chemistry when compared with the complicated branched sugars that are recognised by other C-type lectins. MGL therefore represents a promising target for the design of synthetic peptide vaccines. We have identified that antigen-presenting cells in human skin express MGL and have confirmed that CD14+ dermal DCs might be targeted via MGL. The intracellular fate of MGL following internalisation was tracked by confocal microscopy. MGL traffics through early endosomes to late endosomes/lysosomes, and colocalises with MHC class I and class II. Synthetic glycopeptides were produced incorporating either native O-linked GalNAc or GalNAc residues linked to the peptide chain via non-native ???Click??? chemistry. Biophysical analysis of the ability of both ???Click??? and native glycopeptides peptides with recombinant MGL confirmed the ability of both these peptides to bind MGL. Ongoing work aims to determine whether targeting to MGL using these synthetic peptides results in efficient presentation of antigen to T cells.

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