Skip to main content

Research Repository

Advanced Search

All Outputs (25)

Iodoetherification as a strategy towards sp 3-rich scaffolds for drug discovery (2024)
Journal Article
Barnes, L., Birkinshaw, T. N., Senior, A. J., Siles Brügge, O., Lewis, W., Argent, S. P., …Nortcliffe, A. (2024). Iodoetherification as a strategy towards sp 3-rich scaffolds for drug discovery. Bioorganic and Medicinal Chemistry, 101, Article 117636. https://doi.org/10.1016/j.bmc.2024.117636

Functionalised tetrahydropyran and spirooxepane scaffolds were prepared utilising an iodoetherification strategy and elaborated to demonstrate their potential use in library synthesis. The iodoetherification products could be readily transformed to t... Read More about Iodoetherification as a strategy towards sp 3-rich scaffolds for drug discovery.

Delivery of temozolomide and N3-propargyl analog to brain tumors using an apoferritin nanocage (2020)
Journal Article
Bouzinab, K., Summers, H., Stevens, M. F., Moody, C. J., Thomas, N. R., Gershkovich, P., …Turyanska, L. (2020). Delivery of temozolomide and N3-propargyl analog to brain tumors using an apoferritin nanocage. ACS Applied Materials and Interfaces, 12(11), 12609-12617. https://doi.org/10.1021/acsami.0c01514

Glioblastoma multiforme (GBM) is a grade IV astrocytoma, which is the most aggressive form of brain tumor. The standard of care for this disease includes surgery, radiotherapy and temozolomide (TMZ) chemotherapy. Poor accumulation of TMZ at the tumor... Read More about Delivery of temozolomide and N3-propargyl analog to brain tumors using an apoferritin nanocage.

In search of effective therapies to overcome resistance to Temozolomide in brain tumours (2019)
Journal Article
Grundy, R., Bouzinab, K., Summers, H., Zhang, J., Stevens, M. F. G., Moody, C. J., …Bradshaw, T. D. (2019). In search of effective therapies to overcome resistance to Temozolomide in brain tumours. Cancer Drug Resistance, 2(4), 1018-1031. https://doi.org/10.20517/cdr.2019.64

Glioblastoma multiforme is the most common and lethal brain tumour-type. The current standard of care includes Temozolomide (TMZ) chemotherapy. However, inherent and acquired resistance to TMZ thwart successful treatment. The direct repair protein me... Read More about In search of effective therapies to overcome resistance to Temozolomide in brain tumours.

Origin of the thiopyrone CTP-431 “unexpectedly” isolated from the marine sponge Cacospongia mycofijiensis (2018)
Journal Article
Przeslak, A. D., Inman, M., Lewis, W., & Moody, C. J. (2018). Origin of the thiopyrone CTP-431 “unexpectedly” isolated from the marine sponge Cacospongia mycofijiensis. Journal of Organic Chemistry, 83(17), 10595-10601. https://doi.org/10.1021/acs.joc.8b01258

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 the hemiacetal of latrunculin A,... Read More about Origin of the thiopyrone CTP-431 “unexpectedly” isolated from the marine sponge Cacospongia mycofijiensis.

Nitrogen-bridged, natural product-like octahydrobenzofurans and octahydroindoles: scope and mechanism of bridge-forming reductive amination via caged heteroadamantanes (2018)
Journal Article
Wales, S. M., Adcock, H. V., Lewis, W., Hamza, D., & Moody, C. J. (2018). Nitrogen-bridged, natural product-like octahydrobenzofurans and octahydroindoles: scope and mechanism of bridge-forming reductive amination via caged heteroadamantanes. European Journal of Organic Chemistry, 2018(34), 4696-4704. https://doi.org/10.1002/ejoc.201800962

The biological significance of sp3-rich synthetic scaffolds with natural product-like features yet distinct global frameworks is being increasingly recognised in medicinal chemistry and biochemistry. Taking inspiration from the vast array of bioactiv... Read More about Nitrogen-bridged, natural product-like octahydrobenzofurans and octahydroindoles: scope and mechanism of bridge-forming reductive amination via caged heteroadamantanes.

Visible light mediated oxidation of benzylic sp3 C–H bonds using catalytic 1,4hydroquinone, or its biorenewable glucoside, arbutin, as a pre-oxidant (2018)
Journal Article
Finney, L. C., Mitchell, L. J., & Moody, C. J. (2018). Visible light mediated oxidation of benzylic sp3 C–H bonds using catalytic 1,4hydroquinone, or its biorenewable glucoside, arbutin, as a pre-oxidant. Green Chemistry, 20(10), https://doi.org/10.1039/C7GC03741D

Benzylic ethers undergo a visible light induced C–H activation and oxygen insertion to give the corresponding benzoate esters in moderate to good yields. The conditions employ substoichiometric amounts of 1,4-hydroquinone with copper(II) chloride dih... Read More about Visible light mediated oxidation of benzylic sp3 C–H bonds using catalytic 1,4hydroquinone, or its biorenewable glucoside, arbutin, as a pre-oxidant.

Diastereoselective synthesis of highly substituted, amino- and pyrrolidino-tetrahydrofurans as lead-like molecular scaffolds (2018)
Journal Article
Wales, S. M., Merisor, E., Adcock, H., Pearce, C. A., Strutt, I., Lewis, W., …Moody, C. J. (2018). Diastereoselective synthesis of highly substituted, amino- and pyrrolidino-tetrahydrofurans as lead-like molecular scaffolds. Chemistry - A European Journal, 24(32), 8233-8239. https://doi.org/10.1002/chem.201801046

A series of highly substituted tetrahydrofurans (THFs), decorated with modifiable 2‐aryl, 3‐carboxy and 4‐amino substituents, has been prepared for biological evaluation within the European Lead Factory. Diastereoselective reductive amination of pre‐... Read More about Diastereoselective synthesis of highly substituted, amino- and pyrrolidino-tetrahydrofurans as lead-like molecular scaffolds.

Synthesis of highly substituted 1,2-diazetidin-3-ones, small ring scaffolds for drug discovery (2018)
Journal Article
Santos, M. S., Nortcliffe, A., Lewis, W., Bradshaw, T. D., & Moody, C. J. (in press). Synthesis of highly substituted 1,2-diazetidin-3-ones, small ring scaffolds for drug discovery. Chemistry - A European Journal, https://doi.org/10.1002/chem.201801309

1,2-Diazetidin-3-ones are readily accessible, small ring scaffolds that upon functionalization have the potential to produce diverse 3-dimensional structures for drug discovery. Thus treatment of diazo hydrazides, obtained from simple hydrazides and... Read More about Synthesis of highly substituted 1,2-diazetidin-3-ones, small ring scaffolds for drug discovery.

Synthesis and growth-inhibitory activities of imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamides related to the anti-tumour drug temozolomide, with appended silicon, benzyl and heteromethyl groups at the 3-position (2018)
Journal Article
Cousin, D., Hummersone, M., Bradshaw, T. D., Zhang, J., Moody, C. J., Foreiter, M., …Stevens, M. F. (in press). Synthesis and growth-inhibitory activities of imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamides related to the anti-tumour drug temozolomide, with appended silicon, benzyl and heteromethyl groups at the 3-position. MedChemComm, https://doi.org/10.1039/C7MD00554G

A series of 3-(benzyl-substituted)-imidazo[5,1-d]-1,2,3,5-tetrazines (13) and related derivatives with 3-heteromethyl groups has been synthesised and screened for growth-inhibitory activity in vitro against two pairs of glioma cell lines with temozol... Read More about Synthesis and growth-inhibitory activities of imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamides related to the anti-tumour drug temozolomide, with appended silicon, benzyl and heteromethyl groups at the 3-position.

Densely functionalised spirocyclic oxetane-piperidine scaffolds for drug discovery (2017)
Journal Article
Geary, G. C., Nortcliffe, A., Pearce, C. A., Hamza, D., Jones, G., & Moody, C. J. (in press). Densely functionalised spirocyclic oxetane-piperidine scaffolds for drug discovery. Bioorganic and Medicinal Chemistry, https://doi.org/10.1016/j.bmc.2017.12.012

A spirocyclic, sp3-atom rich oxetane-containing scaffold was synthesised in just two steps via a gold catalysed propargylic alcohol rearrangement. The key gold cyclisation can be undertaken on a 40 g scale allowing the preparation of 419 lead-like co... Read More about Densely functionalised spirocyclic oxetane-piperidine scaffolds for drug discovery.

Development of a series of bis-triazoles as G-quadruplex ligands (2017)
Journal Article
Saleh, M., Laughton, C. A., Bradshaw, T. D., & Moody, C. J. (in press). Development of a series of bis-triazoles as G-quadruplex ligands. RSC Advances, 7, https://doi.org/10.1039/c7ra07257k

Maintenance of telomeres – specialized complexes that protect the ends of chromosomes – is provided by the enzyme complex telomerase, which is a key factor that is activated in more than 80% of cancer cells, but absent in most normal cells. Targeting... Read More about Development of a series of bis-triazoles as G-quadruplex ligands.

C–H insertion as a key step to spiro-oxetanes, scaffolds for drug discovery (2017)
Journal Article
Nicolle, S. M., Nortcliffe, A., Bartrum, H. E., Lewis, W., Hayes, C. J., & Moody, C. J. (in press). C–H insertion as a key step to spiro-oxetanes, scaffolds for drug discovery. Chemistry - A European Journal, https://doi.org/10.1002/chem.201703746

A new route to spiro-oxetanes, potential scaffolds for drug discovery, is described. The route is based on the selective 1,4-C–H insertion reactions of metallocarbenes, generated from simple carbonyl precursors in flow or batch mode, to give spiro-β-... Read More about C–H insertion as a key step to spiro-oxetanes, scaffolds for drug discovery.

Total synthesis of the cyclic dodecapeptides wewakazole and wewakazole B (2017)
Journal Article
Inman, M., Dexter, H. L., & Moody, C. J. (2017). Total synthesis of the cyclic dodecapeptides wewakazole and wewakazole B. Organic Letters, 19(13), 3454-3457. https://doi.org/10.1021/acs.orglett.7b01393

The cyclic dodecapeptides wewakazole and wewakazole B have been synthesized by a divergent strategy via a common tris-proline containing oxazole octapeptide and two separate bisoxazole containing tetrapeptide units, followed by peptide coupling and m... Read More about Total synthesis of the cyclic dodecapeptides wewakazole and wewakazole B.

Total Synthesis of the Post‐translationally Modified Polyazole Peptide Antibiotic Goadsporin (2017)
Journal Article
Dexter, H. L., Williams, H. E., Lewis, W., & Moody, C. J. (2017). Total Synthesis of the Post‐translationally Modified Polyazole Peptide Antibiotic Goadsporin. Angewandte Chemie International Edition, 56(11), 3069-3073. https://doi.org/10.1002/anie.201612103

The structurally unique polyazole antibiotic goadsporin contains six heteroaromatic oxazole and thiazole rings integrated into a linear array of amino acids that also contains two dehydroalanine residues. An efficient total synthesis of goadsporin is... Read More about Total Synthesis of the Post‐translationally Modified Polyazole Peptide Antibiotic Goadsporin.

Stereoselective Synthesis of Functionalized Pyrrolidines by the Diverted N−H Insertion Reaction of Metallocarbenes with β-Aminoketone Derivatives (2016)
Journal Article
Nicolle, S. M., Lewis, W., Hayes, C. J., & Moody, C. J. (2016). Stereoselective Synthesis of Functionalized Pyrrolidines by the Diverted N−H Insertion Reaction of Metallocarbenes with β-Aminoketone Derivatives. Angewandte Chemie International Edition, 55(11), 3749-3753. https://doi.org/10.1002/anie.201511433

A highly stereoselective route to functionalized pyrrolidines from the metal catalyzed diverted N-H insertion of a range of diazocarbonyl compounds with β-aminoketone derivatives is described. A number of catalysts (rhodium(II) carboxylate dimers, co... Read More about Stereoselective Synthesis of Functionalized Pyrrolidines by the Diverted N−H Insertion Reaction of Metallocarbenes with β-Aminoketone Derivatives.

Total Synthesis of the Posttranslationally Modified Polyazole Peptide Antibiotic Plantazolicin?A (2015)
Journal Article
Wada, H., Williams, H. E. L., & Moody, C. J. (2015). Total Synthesis of the Posttranslationally Modified Polyazole Peptide Antibiotic Plantazolicin?A. Angewandte Chemie International Edition, 54(50), 15147-15151. https://doi.org/10.1002/anie.201507062

The power of rhodium carbene methodology in chemistry is demonstrated by the synthesis of a structurally complex polyazole antibiotic. Plantazolicin A, a novel soil bacterium metabolite, comprises a linear array of 10 five-membered rings in two penta... Read More about Total Synthesis of the Posttranslationally Modified Polyazole Peptide Antibiotic Plantazolicin?A.

Synthesis and Intracellular Redox Cycling of Natural Quinones and Their Analogues and Identification of Indoleamine-2,3-dioxygenase (IDO) as Potential Target for Anticancer Activity (2015)
Journal Article
Blunt, C. E., Blunt, C., Torcuk, C., Liu, Y., Lewis, W., Siegel, D., …Moody, C. J. (2015). Synthesis and Intracellular Redox Cycling of Natural Quinones and Their Analogues and Identification of Indoleamine-2,3-dioxygenase (IDO) as Potential Target for Anticancer Activity. Angewandte Chemie International Edition, 54(30), 8740-8745. https://doi.org/10.1002/anie.201503323

Natural quinones, often linked with cellular oxidation processes, also exhibit pronounced biological activity. In particular, the structurally unique isothiazolo-naphthoquinone, aulosirazole, isolated from blue-green alga, possesses selective antitum... Read More about Synthesis and Intracellular Redox Cycling of Natural Quinones and Their Analogues and Identification of Indoleamine-2,3-dioxygenase (IDO) as Potential Target for Anticancer Activity.

Stereoselective synthesis of highly substituted tetrahydrofurans by diverted carbene O–H insertion reaction (2015)
Journal Article
Nicolle, S. M., Lewis, W., Hayes, C. J., & Moody, C. J. (2015). Stereoselective synthesis of highly substituted tetrahydrofurans by diverted carbene O–H insertion reaction. Angewandte Chemie International Edition, 54(29), 8485-8489. https://doi.org/10.1002/anie.201502484

Copper or rhodium catalyzed reaction of diazocarbonyl compounds with β-hydroxyketones gives highly substituted tetrahydrofurans with excellent diastereoselectivity, under mild conditions, in a single step process that starts as a carbene O–H insertio... Read More about Stereoselective synthesis of highly substituted tetrahydrofurans by diverted carbene O–H insertion reaction.

Alkyl halide-free heteroatom alkylation and epoxidation facilitated by a recyclable polymer-supported oxidant for the in-flow preparation of diazo compounds (2015)
Journal Article
Nicolle, S., Hayes, C., & Moody, C. (2015). Alkyl halide-free heteroatom alkylation and epoxidation facilitated by a recyclable polymer-supported oxidant for the in-flow preparation of diazo compounds. Chemistry - A European Journal, 21(12), 4576-4579. doi:10.1002/chem.201500118

Highly reactive metal carbenes, generated from simple ketones via diazo compounds, including diazo?amides and ?phosphonates, using a recyclable reagent in?flow, are transient but versatile electrophiles for heteroatom alkylation reactions and for epo... Read More about Alkyl halide-free heteroatom alkylation and epoxidation facilitated by a recyclable polymer-supported oxidant for the in-flow preparation of diazo compounds.

Seven-membered ring scaffolds for drug discovery: Access to functionalised azepanes and oxepanes through diazocarbonyl chemistry (2015)
Journal Article
Nortcliffe, A., & Moody, C. J. (2015). Seven-membered ring scaffolds for drug discovery: Access to functionalised azepanes and oxepanes through diazocarbonyl chemistry. Bioorganic and Medicinal Chemistry, 23(11), 2730-2735. https://doi.org/10.1016/j.bmc.2015.01.010

© 2015 Elsevier Ltd. All rights reserved. Functionalised azepane and oxepane scaffolds were prepared using diazocarbonyl chemistry and elaborated to show their potential use in library synthesis. Key dicarbonyl containing seven-membered rings were fu... Read More about Seven-membered ring scaffolds for drug discovery: Access to functionalised azepanes and oxepanes through diazocarbonyl chemistry.