A5039806780- Carbohydrate Chemistry and Synthesis
- Chemical Synthesis and Analysis
- Glycosylation and Glycoproteins Research
- Synthetic Organic Chemistry Methods
- Traumatic Brain Injury and Neurovascular Disturbances
- Asymmetric Synthesis and Catalysis
- Chemical Synthesis and Reactions
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Molecular spectroscopy and chirality
- Traditional and Medicinal Uses of Annonaceae
- Advanced MRI Techniques and Applications
- Microbial Natural Products and Biosynthesis
- Synthesis and Biological Evaluation
- Oxidative Organic Chemistry Reactions
- Organic Chemistry Cycloaddition Reactions
- Supramolecular Chemistry and Complexes
- Mitochondrial Function and Pathology
- Phytochemical Studies and Bioactivities
- Legume Nitrogen Fixing Symbiosis
- Coordination Chemistry and Organometallics
- Chemical synthesis and alkaloids
- Enzyme Structure and Function
- Phytochemistry and Bioactive Compounds
- Traumatic Brain Injury Research
University of Cambridge
2009-2023
University Hospitals of Leicester NHS Trust
2018
Leicester General Hospital
2018
Imperial College London
1985-1990
University of British Columbia
1980-1983
King's College London
1979-1980
National Research Council Canada
1980
Indiana University – Purdue University Indianapolis
1956
University Medical Center
1956
Energy metabolism in the human brain is not fully understood. Classically, glucose regarded as major energy substrate. However, lactate (conventionally a product of anaerobic metabolism) has been proposed to act an source, yet whether this occurs man known. Here we show that can indeed utilize source via tricarboxylic acid cycle. We used novel combination 13C-labelled cerebral microdialysis both deliver 13C substrates into and recover metabolites from brain, high-resolution nuclear magnetic...
Increased ‘anaerobic’ glucose metabolism is observed after traumatic brain injury (TBI) attributed to increased glycolysis. An alternative route the pentose phosphate pathway (PPP), which generates putatively protective and reparative molecules. To compare pathways we employed microdialysis perfuse 1,2- 13 C 2 into brains of 15 TBI patients macroscopically normal in six undergoing surgery for benign tumors, simultaneously collect products nuclear magnetic resonance (NMR) analysis. enrichment...
The existence of rotamers in a solution analyte complicates (1)H NMR analysis, especially when the presence diastereomers is also possible. Organic chemists have often responded to this problem by conducting variable-temperature (VT) experiments, changing solvents, or adding complexing agents. Here, with specific examples, we illustrate use simple yet widely overlooked chemical-exchange experiments which allow nonintrusive rapid distinguishment rapidly equilibrating small molecules such as...
A highly convergent total synthesis of the anthelmintic macrolide avermectin B1a 1 is described. The key features this include introduction C(11)–C(15) portion by selective ring opening a symmetrical 1,4-bis-epoxide 4 followed reaction with anion derived from 3-methyl-2-(1-methylpropyl)-6-phenylsulphonylpyran 3 to afford 'northern' C(11)–C(25) fragment 39. Coupling aldehyde unit 42 C(1)–C(10)'southern' 2 was achieved via novel deconjugative vinyl sulphone sequence. Macrolactonisation and...
Following traumatic brain injury, complex cerebral energy perturbations occur. Correlating with unfavourable outcome, high extracellular lactate/pyruvate ratio suggests hypoxic metabolism and/or mitochondrial dysfunction. We investigated whether focal administration of succinate, a tricarboxylic acid cycle intermediate interacting directly the electron transport chain, could improve metabolism. Microdialysis perfused disodium 2,3- 13 C 2 succinate (12 mmol/L) for 24 h into nine sedated...
Abstract A key pathophysiological process and therapeutic target in the critical early post-injury period of traumatic brain injury (TBI) is cell mitochondrial dysfunction; characterised by elevation lactate/pyruvate (L/P) ratio absence hypoxia. We previously showed that succinate can improve extracellular chemistry acute TBI, but it was not clear if this translates to a change downstream energy metabolism. studied effect microdialysis-delivered on state (phosphocreatine/ATP (PCr/ATP)) with...
Abstract The high‐mannose nonasaccharide 1 is part of the glycoprotein gp 120 viral coat HIV‐1. mannan portion this triantennary glycan was prepared by a number consecutive glycosidation steps without need for any protecting‐group manipulation. This achieved carefully tuning reactivity glycosyl donors employing our cyclohexane‐1,2‐diacetal (CDA) methodology. method further extended with one‐pot procedures oligosaccharide synthesis, thus reducing to form protected 21 from monosaccharide...
Modular polyketide synthases (PKSs), for example, the 6-deoxyerythronolide B synthase (DEBS) responsible synthesis of aglycone core macrolide antibiotic erythromycin, generate an impressive diversity asymmetric centers in their products. However, as noted by Celmer, macrolides have same absolute configuration at all comparable stereocenters. Understanding how stereochemistry chain extension is controlled therefore crucial to determining common mechanism action these enzymes. We aimed...
Abstract Three acylated iridoid glycosides ( E )‐6‐ O ‐(2″, 4″‐diacetyl‐3″ ‐ O‐p ‐methoxycinnamoyl)‐α‐ L ‐rhamnopyranosyl catalpol (scopolioside A) 1 ), ‐(2″‐acetyl‐3″, 4″‐di‐ O,O‐p (scrophuloside A 4 ) 2 and ‐(2″,3″‐diacetyl‐4″‐ (scrovalentinoside) 3 have been isolated from the dried seed pods of Scrophularia nodosa by HPLC. Their structures were determined 1D 2D NMR, UV/Vis mass spectroscopy comparison with published data. All three compounds shown in vitro to stimulate growth human dermal...
Biological systems employ multimetallic assemblies to achieve a range of functions. Here we demonstrate the preparation metal-organic cages that contain either homobimetallic or heterobimetallic vertices. These vertices are constructed using 2-formyl-6-diphenylphosphinopyridine, which forms ligands readily bridge between pair metal centers, thus enforcing formation bimetallic coordination motifs. Two pseudo-octahedral homometallic M
Tuning the reactivity of glycosyl donors by selective introduction different protecting and leaving groups enabled highly efficient oligosaccharide synthesis. Utilising both phenylseleno ethylthio glycosides in combination with cyclohexane-1,2-diacetal (CDA) group provided four levels reactivity. One-pot sequential glycosidation three components gave trisaccharides tetrasaccharides.
Biogenic alkenes, which are among the most abundant volatile organic compounds in atmosphere, readily oxidized by ozone. Characterizing reactivity and kinetics of first-generation products these reactions, carbonyl oxides (often named Criegee intermediates), is essential defining oxidation pathways atmosphere but highly challenging due to short lifetime zwitterions. Here, we report development a novel online method quantify atmospherically relevant intermediates (CIs) gas phase stabilization...
Deliberate tuning of the reactivity appropriate glycosyl donors enables nonamannan 1 to be prepared efficiently in a concise manner. Bound through disaccharide linker, is major constituent envelope glycoprotein gp120 human-immunodeficiency virus (HIV). Gp120 plays an important role attachment and penetration target cells by HIV antiviral response.
Metabolic abnormalities occur after traumatic brain injury (TBI). Glucose is conventionally regarded as the major energy substrate, although lactate can also be an source. We compared 3-13C metabolism in TBI with "normal" control and muscle, measuring 13C-glutamine enrichment to assess tricarboxylic acid (TCA) cycle metabolism. Microdialysis catheters brains of nine patients severe TBI, five non-TBI surgical patients, resting muscle (non-TBI) were perfused (24 h brain, 8 muscle) mmol/L...
The use of dibutyltin dimethoxide as an efficient reagent for effecting the selective acylation, alkylation and sulfonylation a variety diols in benzene or toluene is described.
Acid catalysed reaction of monosaccharides with 1,1,2,2-tetramethoxycyclohexane results in selective protection vicinal, diequatorial, diol functionality as a cyclohexane-1,2-diacetal (CDA). This new methodology complements classical cyclic acetal protecting group strategies which general are not able to mask diols such diequatorial stereochemistry. The resulting CDA protected derivatives can be readily functionalised give rapid access numerous key building blocks for oligosaccharide and...
Abstract. Peroxy acids were recently found to be involved in new particle formation the atmosphere and could also substantially contribute towards toxicity. However, a lack of suitable analytical methods for detection characterisation peroxy phase is currently hindering quantitative investigation their contribution these important atmospheric processes. Further development appropriate techniques relevant standards therefore urgently needed. In this study, we synthesised three peroxypinic...
Metabolic dysfunction is a key pathophysiological process in the acute phase of traumatic brain injury (TBI). Although changes glucose metabolism and extracellular lactate/pyruvate ratio are well known, it was hitherto unknown whether these translate to downstream ATP intracellular pH. We have performed first clinical voxel-based vivo phosphorus magnetic resonance spectroscopy (31P MRS) 13 acute-phase major TBI patients versus 10 healthy controls (HCs), at 3T, focusing on eight central 2.5 ×...
Crystal structures of complexes D-xylose isomerase with deoxysugars have been determined. Deoxynojirimycin is a structural analogue alpha-pyranose and mimics the binding these aldose substrates. The structure this complex supports hypothesis that an imidazole group catalyzes ring opening pyranose. steric restrictions in active site enzyme prevent beta-pyranose from same way. For reverse reaction ketoses, anomeric specificity less certain. Dideoxyimino-D-glucitol ketose alpha-D-furanose....
During the synthesis of avermectin B1a (1) C11-C25 spiroacetal portion 2 has been prepared using a novel sequence reactions involving π-allyltricarbonyliron lactone complexes 5 and 6 for preparation cyclic ether sulphone, 8 which in turn was coupled spirocyclised to give 2.