A5022904568- Catalytic C–H Functionalization Methods
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Bioactive Compounds and Antitumor Agents
- Oxidative Organic Chemistry Reactions
- Asymmetric Synthesis and Catalysis
- Catalytic Cross-Coupling Reactions
- Synthesis of Indole Derivatives
- Redox biology and oxidative stress
- Catalytic Alkyne Reactions
- Coordination Chemistry and Organometallics
- Glutathione Transferases and Polymorphisms
- Metal-Catalyzed Oxygenation Mechanisms
- Tryptophan and brain disorders
- Histone Deacetylase Inhibitors Research
- Microbial Natural Products and Biosynthesis
- Synthetic Organic Chemistry Methods
- Protein Degradation and Inhibitors
- Morinda citrifolia extract uses
- Marine Sponges and Natural Products
- Macrophage Migration Inhibitory Factor
- Radical Photochemical Reactions
- Cancer therapeutics and mechanisms
- Clinical Laboratory Practices and Quality Control
- Vanadium and Halogenation Chemistry
University of Nottingham
2010-2022
University of Leeds
2007-2013
Indoles, both naturally occurring and synthetic, exhibit wide-ranging biological activity. Unusual complex molecular architectures occur among their natural derivatives. As a result, this important ring system continues to attract attention from the international chemical community, new methodologies for construction of ever relevant heteroaromatic continue be developed. Unfortunately, many methods frequently start ortho-substituted anilines, thereby greatly restricting availability starting...
To characterize the role of histone deacetylase (HDAC) activity in rheumatoid arthritis (RA) and to evaluate effects MI192, a novel HDAC-3-selective inhibitor, compared with established nonselective HDAC inhibitor trichostatin A (TSA), on proinflammatory cytokine production.Activity acetyltransferase was measured peripheral blood mononuclear cells (PBMCs) from RA patients by spectrophotometric assay, prior after 12 weeks etanercept therapy. The treatment production both healthy PBMCs were...
In a new variation on the Fischer indole synthesis, readily available haloarenes are converted into wide range of indoles in just two steps by halogen-magnesium exchange and quenching with di-tert-butyl azodicarboxylate, followed reaction aldehydes or ketones under acidic conditions. The protocol, which is extended to preparation isosteres, 4- 6-azaindoles thienopyrroles, obviates need prepare potentially toxic aryl hydrazines, simultaneously avoiding undesirable anilines such as naphthylamines.
A Cu(II)-mediated synthesis of indolequinones from the corresponding bromoquinones and enamines is reported. The key oxidative cyclization proceeds in good yield for a broad range substrates can be performed on multigram scale, allowing access to biologically interesting structures.
In a new variation on the Fischer indole synthesis, readily available haloarenes are converted into wide range of indoles in just two steps by halogen-magnesium exchange, quenching with di-tert-butyl azodicarboxylate, followed reaction ketones under acidic conditions.
Abstract Naturally occurring indole‐3‐carbinol and 3,3‐diindolylmethane show bioactivity in a number of disparate disease areas, including cancer, prompting substantial synthetic analogue activity. We describe new approach to highly functionalised derivatives that starts from allene gas proceeds via the combination three‐component Pd 0 ‐catalysed cascade with one‐pot, carbophilic Pt II linked stereoselective acid‐catalysed Mannich–Michael reaction generates complex cyclopropyl...
A series of benzofuranquinones, analogues the marine metabolite annulin A, has been synthesized and evaluated as inhibitors human indoleamine 2,3-dioxygenase (IDO). The synthesis was carried out by copper(II)-mediated reaction bromobenzoquinones with 1,3-dicarbonyl compounds followed functional group interconversions. most potent were 5-methoxy-2-methylbenzofuranquinones containing a CH2OR at position-3 IC50 ∼ 0.2 mM. corresponding hydroquinones inactive. Compounds based on...
The reaction of enamines and bromoquinones in the presence copper(II) acetate potassium carbonate results a regiospecific synthesis indolequinones. is broad scope scalable provides route to core structure that present several biologically interesting natural synthetic compounds.
Summary Radiotherapy is an effective treatment modality for breast cancer but, unfortunately, not all patients respond fully with a significant number experiencing local recurrences. Overexpression of thioredoxin and reductase has been reported to cause multidrug radiation resistance - their inhibition may therefore improve therapeutic efficacy. Novel indolequinone compounds have shown, in pancreatic models, inhibit activity exhibit potent anticancer activity. The present study evaluates,...
The cyclic dodecapeptides wewakazole and B have been synthesized by a divergent strategy via common tris-proline containing oxazole octapeptide two separate bis-oxazole tetrapeptide units, followed peptide coupling macrocyclization. three amino acid fragments are readily accessible rhodium(II)-catalyzed amide N–H insertion of diazocarbonyl compounds, or the cycloaddition rhodium carbenoids with nitriles.
Abstract Diazophosphonates, readily prepared from α‐ketophosphonates by oxidation of the corresponding hydrazones in batch or flow, are useful partners 1,3‐dipolar cycloaddition reactions to alkynes give N ‐H pyrazoles, including first intramolecular examples such a process. The phosphoryl group imbues number desirable properties into diazo 1,3‐dipole. electron‐withdrawing nature stabilizes compound making it easier handle, whilst ability migrate [1,5]‐sigmatropic rearrangement enables its...
An important determinant of the growth inhibitory activity indolequinones against pancreatic cancer cells is substitution on 2-position with 2-unsubstituted derivatives being markedly more potent. A series bearing a range substituents nitrogen and at indolylcarbinyl position was prepared by copper(II)-mediated reaction bromoquinones enamines, followed functional group interconversions. The compounds were then assayed for their ability to inhibit cells. pKa leaving 3-position shown influence...
An intriguing hypothesis that latrunculin A, a well-known natural product, might have undergone transformation into the unprecedented thiopyrone CTP-431 upon long-term storage in methanol is advanced. Thus, opening of hemiacetal followed by E1CB elimination, and dehydration would give polyene could undergo intramolecular Diels-Alder reaction, methanolysis thiazolidinone ring closure thiol addition to an enone. Experimental evidence novel rearrangement can occur presented.
Annulin B, isolated from the marine hydroid Garveia annulata, is a potent inhibitor of tryptophan catabolizing enzyme indoleamine-2,3-dioxygenase (IDO). A synthesis reported pyranonaphthoquinone structure described, in which key step regioselective Diels-Alder reaction between pyranobenzoquinone dienophile and silyl ketene acetal diene.
The thioredoxin (Trx) system, a key antioxidant pathway, represents an attractive target for cancer therapy. This study investigated the chemotherapeutic and radiosensitising effects of novel Trx reductase (TrxR) inhibitor, IQ10, on brain cells underlying mechanisms action. Five cell lines normal type were used. TrxR activity expression assessed by insulin reduction assay Western blotting, respectively. IQ10 cytotoxicity was evaluated using growth curve, resazurin clonogenic assays....
Abstract The successful application of fragment‐based drug discovery strategy for the efficient synthesis phenoxy‐ or phenylamino‐2‐phenyl‐benzofuran, ‐benzoxazole and ‐benzothiazole quinones is described. Interestingly, in final step target compounds, unusual results were observed on regiochemistry reaction bromoquinones with phenol aniline. A theoretical study was carried out better understanding factors that control these reactions. substituted heterocyclic evaluated vitro to determine...
Copper-mediated synthesis of indolequinones from corresponding bromoquinones and enamines is reported. The reaction was optimized in terms oxidant (copper salts), base, solvent. follows the footsteps Murphy [E. Comer, W. S. ARKIVOC, 2003, (vii), 286], who used catalytic amounts CuBr2 air as terminal oxidant. This procedure proved finicky very structure-dependant hands Moody colleagues. Substrate scope well studied, yields range modest to good. Noteworthy inferior reactivity...
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Abstract Novel indolequinones (including QG001, 5-methoxy-1-methyl-3-[(2,4,6-trifluorophenoxy)methyl]-1H-indole-4,7-dione and NJ824, 2-(hydroxymethyl)-5-methoxy-1-methyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione) demonstrated marked anti-proliferative activity in MIAPaCa-2 BxPC-3 pancreatic cancer cells as well colon, melanoma renal cell lines indicated by testing the NCI-60 line screen. In studies using we examined mechanism of action lead IQs results inhibition selenoprotein thioredoxin...
Abstract The halogen‐magnesium exchange of aryl iodides (I) and (VIII) followed by reaction resulting Grignard reagents with azodicarboxylate (II) leads to Boc‐protected hydrazines which reacts easily ketones under acidic conditions afford desired indoles (V) (X), respectively.