A5015912619- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Synthetic Organic Chemistry Methods
- Marine Sponges and Natural Products
- Chemical synthesis and alkaloids
- Crystallography and molecular interactions
- Traditional and Medicinal Uses of Annonaceae
- Microbial Natural Products and Biosynthesis
- Synthesis and Catalytic Reactions
- Catalytic C–H Functionalization Methods
- Asymmetric Synthesis and Catalysis
- Cancer, Hypoxia, and Metabolism
- Cyclopropane Reaction Mechanisms
- Chemical Synthesis and Reactions
- Click Chemistry and Applications
- Sulfur-Based Synthesis Techniques
- Advanced Synthetic Organic Chemistry
- Neuroscience and Neuropharmacology Research
- Chemical Synthesis and Analysis
- Alkaloids: synthesis and pharmacology
- Asymmetric Hydrogenation and Catalysis
- Pharmacological Receptor Mechanisms and Effects
- Adenosine and Purinergic Signaling
- Neuropeptides and Animal Physiology
- HIV/AIDS drug development and treatment
Griffith University
2013-2024
Brisbane School of Theology
2014
Australian National University
2002-2011
Commonwealth Scientific and Industrial Research Organisation
2011
The University of Sydney
2005-2008
University of Cambridge
2001-2005
The University of Queensland
2002
Mitochondrial complex II (CII) has been recently identified as a novel target for anti-cancer drugs. Mitochondrially targeted vitamin E succinate (MitoVES) is modified so that it preferentially localized to mitochondria, greatly enhancing its pro-apoptotic and activity. Using genetically manipulated cells, MitoVES caused apoptosis generation of reactive oxygen species (ROS) in CII-proficient malignant cells but not their CII-dysfunctional counterparts. inhibited the dehydrogenase (SDH)...
As an exceptionally potent antimitotic macrolide, altohyrtin A/spongistatin 1 shows great promise in cancer chemotherapy but its extreme scarcity the natural sponges has halted further preclinical development. A highly stereocontrolled total synthesis, which exploits boron-mediated aldol bond constructions, been realized to provide, for first time, a useful amount of synthetic material.
A sequence of Sonogashira coupling, Pd(II)-catalyzed carbonylative annulation, and benzofuran reduction (Mg, MeOH, NH4Cl) provides a convergent modular synthetic route to trans-2-aryl-2,3-dihydrobenzo[b]furan-3-carboxylates, which are structural feature numerous biologically active natural products. This versatile strategy was applied the formal total synthesis anti-HIV product (+)-lithospermic acid.
A plausible strategy to reduce tumor progress is the inhibition of angiogenesis. Therefore, agents that efficiently suppress angiogenesis can be used for suppression. We tested antiangiogenic potential a mitochondrially targeted analog α-tocopheryl succinate (MitoVES), compound with high propensity induce apoptosis.MitoVES was found kill proliferating endothelial cells (ECs) but not contact-arrested ECs or deficient in mitochondrial DNA, and suppressed vitro by inducing accumulation reactive...
Success in undergraduate chemical experiments requires students to develop knowledge and skills of instrumentation, equipment, techniques. In this technology report, we propose an adaptable user-focused strategy improve students' foundational skill proficiency with laboratory techniques instrumentation. The is composed multiperspective filming experimental activities using mobile phones or professional-level create videos that can be freely viewed by situ during classes on a device (iPad)....
An efficient 8-step enantioselective total synthesis of (+)-angelmarin, starting from commercially available umbelliferone, has been achieved. Key reactions include olefin cross-metathesis and a Shi epoxidation−cyclization sequence.
Stereocontrolled syntheses of the C16–C28 CD-spiroacetal subunit altohyrtin A/spongistatin 1 (1), relying on kinetic and thermodynamic control spiroacetal formation, are described. The approach resulted in a slight preference (60 : 40) for desired isomer. allowed ready access to 2 by acid-promoted equilibration, chromatographic separation C23 epimers resubjection undesired isomer equilibration conditions. This scalable synthetic sequence provided multi-gram quantities 2, thus enabling...
The antimitotic marine macrolide altohyrtin A/spongistatin 1 (1) has been synthesised in a highly convergent and stereocontrolled manner, thus contributing to the replenishment of largely exhausted material from initial isolation work. Coupling AB- CD-spiroacetal subunits by stereoselective aldol reaction was achieved using either lithium (67 : 33 dr) or boron enolate (90 10 dr). A (Z)-selective Wittig coupling used unite northern hemisphere aldehyde 2 with southern phosphonium salt 3....
The convergent synthesis of the C1–C15 AB-spiroacetal subunit 2 altohyrtin A/spongistatin 1 (1) is described. This highly stereocontrolled relies on matched boron aldol reactions chiral methyl ketones, under Ipc2BCl mediation, to establish C5, C9 and C11 stereocentres, formation desired thermodynamic spiroacetal acidic conditions. scalable synthetic sequence developed provided access multi-gram quantities 2, thus enabling successful completion total 1, as reported in Part 4.
Thiaplakortone A (3a), an antimalarial natural product, was prepared by operationally simple and scalable synthesis. In our efforts to deliver a lead compound with improved potency, metabolic stability, selectivity, the synthesis diverted access series of analogues. Compounds 3a–d showed nanomolar activity against chloroquine-sensitive (3D7) Plasmodium falciparum line were more active chloroquine- mefloquine-resistant (Dd2) P. line. All compounds are "Rule-of-5" compliant, we show that...
A series of amide (8–32, 40–45) and urea (33, 34, 36–39) analogues based on the thiaplakortone natural product scaffold were synthesised screened for in vitro antimalarial activity against chloroquine-sensitive (3D7) chloroquine- mefloquine-resistant (Dd2) Plasmodium falciparum parasite lines. Several displayed potent inhibition P. growth (IC50 <500 nM) good selectivity versus human neonatal foreskin fibroblast cells (selectivity index >100). Two these compounds, 8 33, exhibited aqueous...
The fully functionalised C29–C51 southern hemisphere of altohyrtin A/spongistatin 1 (1), incorporating the E- and F-ring tetrahydropyran rings unsaturated side chain, has been synthesised in a highly convergent stereocontrolled manner. Key steps synthesis this phosphonium salt include four diastereoselective, substrate-controlled, boron aldol reactions to establish key C–C bonds accompanying stereocentres, where introduction chlorodiene chain C47 hydroxyl-bearing centre were realised by...
Cathinone and its synthetic analogues are known compounds of clandestine interest. Investigation into novel pathways for synthesising cathinone derivatives has potential forensic analysis tracking. The Neber rearrangement commercially available phenylpropanones that were evaluated yielded amides described herein was not viable synthesis derivatives. Whereas the modified via stable aziridine salts subsequent treatment with acid, gave in poor to low yields (2–17%). Assessment reagents,...
Despite significant endeavor having been applied to identify effective therapies treat glioblastoma (GBM), survival outcomes remain intractable. The greatest nonsurgical benefit arises from radiotherapy, though tumors typically recur due robust DNA repair. Patients could therefore with the potential prevent repair and synergize radiotherapy. In this work, we investigated of salinomycin enhance radiotherapy further uncover novel dual functions ionophore induce damage repair.In vitro primary...
Abstract Owing to the key role of trehalose in pathogenic organisms, there has recently been growing interest metabolism for therapeutic purposes. Trehalose-6-phosphate phosphatase (TPP) is a pivotal enzyme most prominent biosynthesis pathway (OtsAB). Here, we compare characteristics recombinant TPPs from five important nematode and bacterial pathogens, including three novel members this protein family. Analysis kinetics trehalose-6-phosphate hydrolysis reveals that all enzymes display...
A series of competition experiments has revealed that selective cleavage N-benzyl-protected secondary amines can be achieved with triphosgene, thereby providing a useful range carbamoyl chlorides.