Publications (78) View all
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Article: Potential sources of high value chemicals from leaves, stems and flowers of Miscanthus sinensis 'Goliath' and Miscanthus sacchariflorus.
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ABSTRACT: Society demands chemicals from sustainable sources. Identification of commercially important chemicals in crops increases value in biorefineries and reduces reliance on petrochemicals. Miscanthus sinensis and Miscanthus sacchariflorus are high-yielding distinct plants, which are sources of high-value chemicals and bioethanol through fermentation. Cinnamates in leaves, stems and flowers were analysed by LC-ESI-MS(n). Free phenols were extracted and separated chromatographically. More than twenty hydroxycinnamates were identified by UV and LC-ESI-MS(n). Several cinnamate hexosides were detected in the M. sinensis flower and in M. sacchariflorus (leaf and stem). Hydroxybenzoic acids and their hexosides were observed in leaf and stem of M. sacchariflorus. Higher concentrations of 3-feruloylquinic acid were observed in M. sacchariflorus stem, suggesting a role in cell-wall biosynthesis. This technique can be used to screen plants in a mapping family to identify genotypes/species with high concentrations of phenols. Plants with low concentrations of antimicrobial phenols may be good feedstocks for fermentation.Phytochemistry 05/2013; · 3.35 Impact Factor -
Article: α-Methylacyl-CoA racemase (AMACR): Metabolic enzyme, drug metabolizer and cancer marker P504S.
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ABSTRACT: α-Methylacyl-CoA racemase (AMACR; P504S) catalyzes a key chiral inversion step in the metabolism of branched-chain fatty acids, ibuprofen and related drugs. Protein levels are increased in all prostate and some other cancer cells and it is used as a marker (P504S). The enzyme requires no cofactors and catalyzes its reaction by a stepwise 1,1-proton transfer via an enolate intermediate. The biological role of AMACR in cancer is complex, linking lipid metabolism with nuclear receptor (e.g. FXR and PPAR) activity and expression of enzymes such as cyclooxygenase-2 (COX-2). The roles of the various splice variants and the effects of single-nucleotide polymorphisms (SNPs) in cancers are discussed. A number of rationally designed AMACR inhibitors have been reported in the literature as potential cancer treatments. The opportunities and challenges for development of acyl-CoA esters as inhibitors are discussed from a medicinal chemical viewpoint. Other challenges for drug development include the problems in assaying enzymatic activity and the prediction of structure-activity relationships (SAR). Inhibitors of AMACR have potential to provide a novel treatment for castrate-resistant prostate cancers but this potential can only be realized once the biology is well understood. Recent work on the role of AMACR in parasitic diseases is also reviewed.Progress in lipid research 01/2013; · 10.67 Impact Factor -
Article: N3-alkylation during formation of quinazolin-4-ones from condensation of anthranilamides and orthoamides.
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ABSTRACT: Dimethylformamide dimethylacetal (DMFDMA) is widely used as a source of electrophilic one-carbon units at the formate oxidation level; however, electrophilic methylation with this reagent is previously unreported. Reaction of anthranilamide with DMFDMA at 150 °C for short periods gives mainly quinazolin-4-one. However, prolonged reaction with dimethylformamide di(primary-alkyl)acetals leads to subsequent alkylation at N(3). 3-Substituted anthranilamides give 8-substituted 3-alkylquinazolin-4-ones. Condensation of anthranilamides with dimethylacetamide dimethylacetal provides 2,3-dimethylquinazolin-4-ones. In these reactions, the source of the N(3)-alkyl group is the O-alkyl group of the orthoamides. By contrast, reaction with the more sterically crowded dimethylformamide di(isopropyl)acetal diverts the alkylation to the oxygen, giving 4-isopropoxyquinazolines, along with N(3)-methylquinazolin-4-ones where the methyl is derived from N-Me of the orthoamides. Reaction of anthranilamide with the highly sterically demanding dimethylformamide di(t-butyl)acetal gives largely quinazolin-4-one, whereas dimethylformamide di(neopentyl)acetal forms a mixture of quinazolin-4-one and N(3)-methylquinazolin-4-one. The observations are rationalised in terms of formation of intermediate cationic electrophiles (alkoxymethylidene-N,N-dimethylammonium) by thermal elimination of the corresponding alkoxide from the orthoamides. These are the first observations of orthoamides as direct alkylating agents.Organic & Biomolecular Chemistry 09/2011; 9(17):6089-99. · 3.70 Impact Factor -
Article: Isolation, identification and quantitation of hydroxycinnamic acid conjugates, potential platform chemicals, in the leaves and stems of Miscanthus × giganteus using LC-ESI-MSn.
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ABSTRACT: Miscanthus×giganteus is a source of platform chemicals and bioethanol through fermentation. Cinnamates in leaves and stems were analysed by LC-ESI-MS(n). Free phenols were extracted and separated chromatographically. More than 20 hydroxycinnamates were identified by UV and LC-ESI-MS(n). Comparative LC-MS studies on the leaf extract showed isomers of O-caffeoylquinic acid (3-CQA, 4-CQA and 5-CQA), O-feruloylquinic acid (3-FQA, 4-FQA and 5-FQA) and para-coumaroylquinic acid (3-pCoQA and 5-pCoQA). Excepting 3-pCoQA, all were also detected in stem. 5-CQA dominated in leaf; a mandelonitrile-caffeoylquinic acid dominated in stem. Three minor leaf components were distinguished by fragmentation patterns in a targetted MS(2) experiment as dicaffeoylquinic acid isomers. Others (M(r) 516) were tentatively identified as hexosylcaffeoyl-quinates. Three positional isomers of O-caffeoylshikimic acid were minor components. p-Hydroxybenzaldehyde was also a major component in stem. This is the first report of the hydroxycinnamic acid profile of leaves and stems of M.×giganteus.Phytochemistry 09/2011; 72(18):2376-84. · 3.35 Impact Factor -
Article: Chiral inversion of 2-arylpropionyl-CoA esters by human α-methylacyl-CoA racemase 1A (P504S)--a potential mechanism for the anti-cancer effects of ibuprofen.
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ABSTRACT: Metabolic chiral inversion of 2-arylpropanoic acids (2-APAs;'profens'), such as ibuprofen, is important for pharmacological activity. Several 2-APA-CoA esters were good racemisation substrates for human AMACR 1A, suggesting a common chiral inversion pathway for all 2-APAs and an additional mechanism for their anti-cancer properties.Chemical Communications 07/2011; 47(26):7332-4. · 6.17 Impact Factor
