89,483 results

  • Synthesis of a 2-deoxyglucosyl analogue of medermycin

    Brimble, MA; Brenstrum, Timothy (2001)

    Journal article
    The University of Auckland Library

    The synthesis of a 2-deoxyglucosyl analogue 6 of the C-glycosylpyranonaphthoquinone antibiotic medermycin 1 is described. The key 3-acetyl-6-(2-deoxyglucosyl)-1,4-naphthoquinone 7 is prepared from 6-(2-deoxyglucosyl)-1,4-naphthoquinone 21, which in turn is available by C-glycosylation of naphthol 18 with glycosyl donor 12 using BF3??Et2O in acetonitrile followed by oxidative demethylation of the derived methyl ether 20. An acetyl group is then introduced at C-3 on naphthoquinone 21 by reductive monomethylation to naphthol 22, ortho bromination to bromide 24, methylation to 9, followed by Stille coupling with ??-ethoxyvinyltributyltin (and hydrolysis) to afford the 3-acetylnaphthalene 8. Addition of 2-(trimethylsilyloxy)furan 13 to naphthoquinone 7, formed from oxidative demethylation of the naphthalene 8, affords the furofuran adducts 25 and 26 as an inseparable mixture of diastereomers. Oxidative rearrangement of this diastereomeric mixture using cerium(IV) ammonium nitrate affords the unstable diastereomeric lactols 27 and 28 also as a 1:1 inseparable mixture. Reduction of these lactols 27 and 28 with triethylsilane and BF3??Et2O at ???10 ??C affords ethers 29 and 30 as a 1:1 mixture. Finally, conversion of ethers 29 and 30 to a 1:1 diastereomeric mixture of medermycin analogues 6 and 31 is achieved by treatment with boron tribromide which effects removal of the methoxy group at C-7, the benzyl ethers on the 2-deoxyglucose residue, and epimerisation at C-5.

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  • Synthesis of an Arginine Tagged [Cys155-Arg180] Fragment of NY-ESO-1: Elimination of an Undesired By-product using "In House" Resins

    Harris, Paul; Brimble, Margaret (2009)

    Journal article
    The University of Auckland Library

    During the solid-phase synthesis of a peptide fragment derived from the cancer protein NY-ESO-1 incorporating a solubilising arginine tag, a significant by-product was obtained that lacked the arginine tag. The formation of this by-product (and others) was highly dependant on the quality of the resin used and was completely removed when the resin was synthesized ???in house'.

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  • Synthesis of azido analogues of medermycin

    Brimble, MA; Davey, RM; McLeod, MD (2002)

    Journal article
    The University of Auckland Library

    The synthesis of azido analogues 2a,2b of the pyrano-naphthoquinone antibiotic medermycin I has been achieved in eight steps from naphthol 8 and azido glycosyl sugar 7 in 9.3% overall yield. Key steps include the direct (BF3Et2O)-Et-. promoted C-glyc

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  • Synthesis of cyclic proline-containing peptides via ring-closing metathesis

    Harris, Paul; Brimble, MA; Gluckman, Peter (2003)

    Journal article
    The University of Auckland Library

    Several dienes embedded in di- and tripeptides which incorporate proline have been prepared and subjected to ring-closing metathesis. Bicyclic peptides of well-defined amide geometry and of varying ring sizes were prepared. Several limitations of the

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  • Synthesis of Enantiopure Bicyclic alpha,alpha-Disubstituted Spirolactams via Asymmetric Birch Reductive Alkylation

    Gueret, Stephanie; O'Connor, Patrick; Brimble, Margaret (2009)

    Journal article
    The University of Auckland Library

    The synthesis of enantiopure bicyclic ??,??-disubstituted spirolactams is described using a diastereoselective Birch reductive alkylation as the key step. Hydrogenation of the resultant alkylated cyclohexadienes followed by intramolecular cyclization provides access to enantiopure 8-azaspiro[5.6]dodecan-7-ones.

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  • Synthesis of fluorescein-labelled O-mannosylated peptides as components for synthetic vaccines: comparison of two synthetic strategies

    Brimble, Margaret; Kowalczyk, Renata; Harris, PWR; Dunbar, Peter; Muir, VJ (2008)

    Journal article
    The University of Auckland Library

    Mannose-binding proteins on the surface of antigen-presenting cells (APCs) are capable of recognizing and internalizing foreign agents in the early stages of immune response. These receptors offer a potential target for synthetic vaccines, especially vaccines designed to stimulate T cells. We set out to synthesize a series of fluorescein-labelled O-mannosylated peptides using manual solid phase peptide synthesis (SPPS) on pre-loaded Wang resin, in order to test their ability to bind mannose receptors on human APCs in vitro. A flexible and reliable method for the synthesis of fluorescein-labelled O-mannosylated glycopeptides was desired in order to study their lectin-binding properties using flow cell cytometry. Two synthetic strategies were investigated: incorporation of a fluorescein label into the peptide chain via a lysine side chain ??-aminogroup at the final stage of standard Fmoc solid phase peptide synthesis or attachment of the fluorescein label to the N??-aminogroup of a lysine with further incorporation of a mannosylated peptide unit through the side chain N??-aminogroup. The latter strategy proved more effective in that it facilitated SPPS by positioning the growing mannosylated peptide chain further removed from the fluorescein label.

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  • Synthesis of Macrocyclic Analogues of the Neuroprotective Agent Glycyl-L-Prolyl-L-Glutamic acid (GPE)

    Harris, Paul; Brimble, Margaret (2006)

    Journal article
    The University of Auckland Library

    The syntheses of seven macrocyclic analogues of the neuroprotective tripeptide glycyl-L-prolyl-L-glutamic acid (GPE) 1 are described. Macrocycles 6 and 7 mimic the cis conformer of GPE whereas macrocycles 2???5, 8, and 9 mimic the trans conformer of GPE. The macrocyclic peptides of well-defined geometry were prepared via Grubbs ring closing metathesis of an appropriate diene precursor. In turn each of the diene precursors were prepared from the readily available allyl-substituted amino acid building blocks 12, 13, 14, 27, 36 and 51.

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  • Synthesis of naphthyl C-glycosides of rearranged tri-O-benzyl-2-deoxy-D-glucose

    Brimble, MA; Brenstrum, Timothy (2000)

    Journal article
    The University of Auckland Library

    C-Glycosylation of 3-bromonaphthol 4 with benzyl-protected glycosyl donor 19 afforded rearranged bicyclic acetal 24 in which the glycosyl donor had undergone an unusual 1,6-hydride shift. Use of the regioisomeric 2-bromonaphthol 6 with the same glyco

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  • Synthesis of Natural Products Containing Spiroketals via Intramolecular Hydrogen Abstraction

    Sperry, Jonathan; Liu, Y; Brimble, Margaret (2010)

    Journal article
    The University of Auckland Library

    Although known for over a quarter of a century, the oxidative radical cyclisation route to spiroketals has found limited use in natural product synthesis in comparison to classical approaches. Its successful application in this field of research forms the subject of this perspective.

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  • Synthesis of proline-modified analogues of the neuroprotective agent glycyl-l-prolyl-glutamic acid (GPE)

    Harris, Paul; Brimble, MA; Muir, Victoria; Lai, MYH; Trotter, NS; Callis, DJ (2005)

    Journal article
    The University of Auckland Library

    The synthesis of ten proline-modified analogues of the neuroprotective tripeptide GPE is described. Five of the analogues incorporate a proline residue with a hydrophobic group at C-2 and two further analogues have this side chain locked into a spirolactam ring system. The pyrrolidine ring was also modified by replacing the ??-CH2 group with sulfur and/or incorporation of two methyl groups at C-5.

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  • Synthesis of Spiroacetal-Nucleosides as Privileged Natural Product-like Scaffolds

    Choi, Ka; Brimble, Margaret (2009)

    Journal article
    The University of Auckland Library

    The elaboration of a 6,6-spiroacetal scaffold to incorporate a nucleoside unit at the anomeric position is described. The novel spiroacetal-nucleoside hybrids 11 were generated via nucleosidation of acetoxy-spiroacetal10 with a series of silylated nucleobases under Vorbr??ggen conditions.

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  • Synthesis of the bis-spiroacetal C-25-C-40 moiety of the antimitotic agent spirastrellolide B using a bis-dithiane deprotection/spiroacetalisation sequence

    Chen, JLY; Brimble, Margaret (2010)

    Journal article
    The University of Auckland Library

    Use of a bis-dithiane deprotection-tandem bis-spiroacetalisation sequence was key to the successful synthesis of the [5,6,6]-bis-spiroacetal of the antimitotic agent spirastrellolide B, achieved in a highly convergent fashion involving successive dithiane alkylations.

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  • Synthesis of the Bis-spiroacetal Moiety of Spirolides B and D

    Brimble, MA; Meilert, Kai (2005)

    Journal article
    The University of Auckland Library

    An enantioselective synthesis of the bis-spiroacetal fragment of spirolides B and D is reported. The carbon framework was constructed via Barbier reaction of dihydropyran 3 with aldehyde 4, followed by a double oxidative radical cyclization to construct the bis-spiroacetal. A silyl-modified Prins cyclization and enantioselective crotylation successfully installed the stereocenters in the cyclization precursor. The initial unsaturated bis-spiroacetals 2a???d underwent equilibration during epoxidation to trans-epoxide 14 that was converted to a tertiary alcohol.

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  • Synthesis of the pyranonaphthoquinones dehydroherbarin, (+)-astropaquinone B and (+)-astropaquinone C en route to ascomycones A and B

    Wadsworth, AD; Sperry, Jonathan; Brimble, Margaret (2010)

    Journal article
    The University of Auckland Library

    The total syntheses of the pyranonaphthoquinone natural products dehydroherbarin, (+)-astropaquinone B and (+)-astropa??quinone C are described. A late stage oxidation strategy employed for the synthesis of the astropaquinones was not amenable to the conversion of dehydroherbarin into the ascomycones. The syntheses of astropaquinones B and C reported herein constitute the first total syntheses and their absolute stereochemistry was determined to be (1R,3S).

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  • Synthesis of the Spiroacetal-Containing Anti-Helicobacter Pylori Agents CJ-12,954 and CJ-13,014

    Brimble, Margaret; Bryant, Christina (2006)

    Journal article
    The University of Auckland Library

    The first synthesis of the spiroacetal-containing anti-Helicobacter pylori agents ent-CJ-12,954 and ent-CJ-13,014 is reported based on the union of a heterocycle-activated spiroacetal-containing sulfone fragment with a phthalide-containing aldehyde fragment; comparison of the 1H and 13C NMR data, optical rotations and HPLC retention times of the synthetic compounds (3S,2???S,5???S,7???S)-(1a) and (3S,2???S,5???R,7???S)-(2a) and the (3R)-diastereomers (3R,2???S,5???S,7???S)-(1b) and (3R,2???S,5???R,7???S)-(2b) with the naturally occurring compounds established that the synthetic isomers (1a) and (2a) were in fact enantiomeric to the natural products CJ-12,954 and CJ-13,014.

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  • Total Synthesis and Absolute Configuration of (-)-Berkeleyamide A

    Sperry, Jonathan; Harris, Eric; Brimble, Margaret (2010)

    Journal article
    The University of Auckland Library

    A chiral-pool approach to (???)-berkeleyamide A 1 based on a diastereoselective nitrile oxide [3 + 2]-cycloaddition completes the first total synthesis establishing the absolute stereochemistry of the natural product.

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  • Mutations in inhibin and activin genes associated with human disease

    Shelling, Andrew (2012)

    Journal article
    The University of Auckland Library

    Inhibins and activins are members of the transforming growth factor (TGF??) superfamily, that includes the TGF??s, inhibins and activins, bone morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs). The family members are expressed throughout the human body, and are involved in the regulation of a range of important functions. The precise regulation of the TGF?? pathways is critical, and mutations of individual molecules or even minor alterations of signalling will have a significant affect on function, that may lead to development of disease or predisposition to the development of disease. The inhibins and activins regulate aspects of the male and female reproductive system, therefore, it is not surprising that most of the diseases associated with abnormalities of the inhibin and activin genes are focused on reproductive disorders and reproductive cancers. In this review, I highlight the role of genetic variants in the development of conditions such as premature ovarian failure, pre-eclampsia, and various reproductive cancers. Given the recent advances in human genetic research, such as genome wide association studies and next generation sequencing, it is likely that inhibins and activins will be shown to play more important roles in a range of human genetic diseases in the future.

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  • An Attributional Analysis of Reactions to Poverty: The Political Ideology of the Giver and the Perceived Morality of the Receiver

    Weiner, B; Osborne, Daniel; Rudolph, U (2011-05)

    Journal article
    The University of Auckland Library

    An attributional analysis of reactions to poverty is presented. The article begins by discussing the perceived causes of poverty and their taxonomic properties (locus, stability, and controllability). One antecedent of causal beliefs, political ideology, is then examined in detail, followed by a review of the effects of causal beliefs on emotions and behavior. It is contended that helping the poor is a moral issue, but the moral evaluation concerns the targeted recipient of aid rather than the potential help giver. Persons perceived as responsible for their plight, a dominant construal for conservatives, elicit anger and neglect. In contrast, those seen as not responsible for their financial hardship, an outlook predominantly endorsed by liberals, arouse sympathy and help giving. Sympathy is the most important proximal determinant of aid. This analysis is extended to reactions to achievement failure, abortion, and rape. Policy implications are also examined.

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  • From cloud computing to cloud manufacturing

    Xu, Xun (2012-02)

    Journal article
    The University of Auckland Library

    Cloud computing is changing the way industries and enterprises do their businesses in that dynamically scalable and virtualized resources are provided as a service over the Internet. This model creates a brand new opportunity for enterprises. In this paper, some of the essential features of cloud computing are briefly discussed with regard to the end-users, enterprises that use the cloud as a platform, and cloud providers themselves. Cloud computing is emerging as one of the major enablers for the manufacturing industry; it can transform the traditional manufacturing business model, help it to align product innovation with business strategy, and create intelligent factory networks that encourage effective collaboration. Two types of cloud computing adoptions in the manufacturing sector have been suggested, manufacturing with direct adoption of cloud computing technologies and cloud manufacturing - the manufacturing version of cloud computing. Cloud computing has been in some of key areas of manufacturing such as IT, pay-as-you-go business models, production scaling up and down per demand, and flexibility in deploying and customizing solutions. In cloud manufacturing, distributed resources are encapsulated into cloud services and managed in a centralized way. Clients can use cloud services according to their requirements. Cloud users can request services ranging from product design, manufacturing, testing, management, and all other stages of a product life cycle.

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  • Where there's a will, is there a way? Is New Zealand's publicly funded health sector able to steer towards population health?

    Tenbensel, Timothy; Cumming, J; Ashton, Toni; Barnett, P (2008)

    Journal article
    The University of Auckland Library

    Since 2000, the substantive focus of health policy in New Zealand has been closely aligned to the agendas of improving population health and reducing health inequalities. Health system restructuring, through the introduction of locally based and partially elected District Health Boards (DHBs), was the structural mechanism chosen for reorienting the health sector towards population health. Strategic planning at the DHB level was the key mechanism by which central government population health objectives would be translated into local action. This analysis of the early years of elected DHBs (2001???2005) sets out to answer the following broad questions: (i) did strategic planning by District Health Boards reflect an orientation to population health?; (ii) to what extent was strategic planning towards population health shaped by community participation and input?; (iii) to what extent did strategic planning lead to a re-prioritisation of resources? These questions were explored as part of a larger research project investigating the introduction and implementation of the DHB system. Data were collected from over 350 interviews of local and national stakeholders, and two surveys of DHB Members between 2002 and 2004???2005. Overall, DHBs demonstrated the ???will??? to engage in strategic decision-making processes to enhance population health but have difficulty in finding the ???way???. The priorities and requirements of central government and the weight of institutional history were found to be the most influential factors on DHB decision-making and practice, with flexibility and innovation only exercised at the margins. This raises the key question of whether there is the governmental capacity at the local level to adequately address nationally determined population health policy priorities.

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