Search

Your search keyword '"Croft, Rosemary A."' showing total 26 results
Start Over Author "Croft, Rosemary A."
26 results on '"Croft, Rosemary A."'

2. Exploring oxetane isosteres for drug discovery through the catalytic generation of oxetanyl carbocations

Author

Croft, Rosemary and Bull, James

Subjects
547
Abstract

Oxetanes are valuable motifs for modulating the metabolic susceptibility and physicochemical properties of medicinally promising compounds, as well as replacement motifs for carbonyl, gem-dimethyl and methylene units. For this reason, development of methodology to synthesise novel oxetane derivatives through efficient and robust routes is highly desirable. In this thesis, the preparation of novel oxetane scaffolds through the in situ generation of oxetanyl carbocations is explored. First, the preparation of 3,3-diaryloxetanes, designed as isosteres for benzophenone and diarylmethane derivatives, through a catalytic Friedel–Crafts reaction is described. Using a lithium catalyst, 3,3-diaryloxetanes and dihydrobenzofuran scaffolds are both selectively prepared in one step by reaction of oxetan-3-ols with phenols. A scope of both scaffolds is exemplified along with further derivatisations of the 3,3 diaryloxetane motif. Studies into the mechanism of the reaction using 1H NMR spectroscopy to observe oxetane ether intermediates are described. The same lithium catalyst is applied to the thiol alkylation of oxetanols with sulfides towards a wide range of novel 3-sulfanyloxetanes in excellent yields (up to 91%). The sulfide linker presents a versatile site for further derivatisation leading to novel oxetane containing structural classes and building blocks such as sulfoxides, sulfones, sodium sulfinate salts and sulfonyl fluorides. The reactivity of the oxetane-containing sulfinate salts and sulfonyl fluorides is described. In particular, oxetane-containing sulfonyl fluorides show exciting novel reactivity giving 3-aminooxetanes when reacted with a variety of amines instead of the expected sulfonamides. Studies into this unprecedented reactivity are described and compared to other alkyl sulfonyl fluorides. The final section of this thesis provides full experimental details and data for all compounds synthesised during the course of this research.

Published
2018
Full Text
View/download PDF

5. Lithium‐Catalyzed Thiol Alkylation with Tertiary and Secondary Alcohols: Synthesis of 3‐Sulfanyl‐Oxetanes as Bioisosteres

Author

Croft, Rosemary A., Mousseau, James J., Choi, Chulho, and Bull, James A.

Subjects
Alkylation, oxetanes, Alcohols, Communication, sulfides, bioisosteres, oxygen heterocycles, Cysteine, Sulfhydryl Compounds, Sulfones, Heterocycles, homogeneous catalysis, Communications
Abstract

3‐Sulfanyl‐oxetanes are presented as promising novel bioisosteric replacements for thioesters or benzyl sulfides. From oxetan‐3‐ols, a mild and inexpensive Li catalyst enables chemoselective C−OH activation and thiol alkylation. Oxetane sulfides are formed from various thiols providing novel motifs in new chemical space and specifically as bioisosteres for thioesters due to their similar shape and electronic properties. Under the same conditions, various π‐activated secondary and tertiary alcohols are also successful. Derivatization of the oxetane sulfide linker provides further novel oxetane classes and building blocks. Comparisons of key physicochemical properties of the oxetane compounds to selected carbonyl and methylene analogues indicate that these motifs are suitable for incorporation into drug discovery efforts.

Published
2017

7. Catalytic Friedel‐Crafts Reactions on Saturated Heterocycles and Small Rings for sp3‐sp2 Coupling of Medicinally Relevant Fragments

Author

Croft, Rosemary A., primary, Dubois, Maryne A. J., additional, Boddy, Alexander J., additional, Denis, Camille, additional, Lazaridou, Anna, additional, Voisin‐Chiret, Anne Sophie, additional, Bureau, Ronan, additional, Choi, Chulho, additional, Mousseau, James J., additional, and Bull, James A., additional

Published
2019
Full Text
View/download PDF

8. Modular Access to Substituted Azocanes via a Rhodium-Catalyzed Cycloaddition–Fragmentation Strategy

Author

Shaw, Megan H., Croft, Rosemary A., Whittingham, William G., and Bower, John F.

Subjects
Heterocyclic Compounds, 1-Ring, Cycloaddition Reaction, Phosphines, Communication, Rhodium, Cyclopentanes, Alkenes, Catalysis
Abstract

A short entry to substituted azocanes by a Rh-catalyzed cycloaddition-fragmentation process is described. Specifically, exposure of diverse N-cyclopropylacrylamides to phosphine-ligated cationic Rh(I) catalyst systems under a CO atmosphere enables the directed generation of rhodacyclopentanone intermediates. Subsequent insertion of the alkene component is followed by fragmentation to give the heterocyclic target. Stereochemical studies show, for the first time, that alkene insertion into rhodacyclopentanones can be reversible.

Published
2015

9. Investigating 3,3-diaryloxetanes as potential bioisosteres through matched molecular pair analysisElectronic supplementary information (ESI) available: Spectroscopic data of synthesized compounds, and experimental procedures for ADME data, and table of log Ddata. See DOI: 10.1039/d1md00248a

Author

Dubois, Maryne A. J., Croft, Rosemary A., Ding, Yujie, Choi, Chulho, Owen, Dafydd R., Bull, James A., and Mousseau, James J.

Abstract

Oxetanes have received increasing interest in medicinal chemistry as attractive polar and low molecular weight motifs. The application of oxetanes as replacements for methylene, methyl, gem-dimethyl and carbonyl groups has been demonstrated to often improve chemical properties of target molecules for drug discovery purposes. The investigation of the properties of 3,3-diaryloxetanes, particularly of interest as a benzophenone replacement, remains largely unexplored. With recent synthetic advances in accessing this motif we studied the effects of 3,3-diaryloxetanes on the physicochemical properties of ‘drug-like’ molecules. Here, we describe our efforts in the design and synthesis of a range of drug-like compounds for matched molecular pair analysis to investigate the viability of the 3,3-diaryloxetane motif as a replacement group in drug discovery. We conclude that the properties of the diaryloxetanes and ketones are similar, and generally superior to related alkyl linkers, and that diaryloxetanes provide a potentially useful new design element.

Published
2021
Full Text
View/download PDF

11. Catalytic Friedel‐Crafts Reactions on Saturated Heterocycles and Small Rings for sp3‐sp2 Coupling of Medicinally Relevant Fragments.

Author

Croft, Rosemary A., Dubois, Maryne A. J., Boddy, Alexander J., Denis, Camille, Lazaridou, Anna, Voisin‐Chiret, Anne Sophie, Bureau, Ronan, Choi, Chulho, Mousseau, James J., and Bull, James A.

Subjects
*FRIEDEL-Crafts reaction, *HETEROCYCLIC compounds, *CYCLOBUTANE, *HOMOGENEOUS catalysis, *LEWIS acids
Abstract

gem‐Diarylheterocycles display a wide range of biological activity. Here we present a systematic study into the formation of 4‐ to 6‐membered O‐ and N‐heterocycles and cyclobutanes bearing the diaryl motif through a catalytic Friedel–Crafts reaction from the corresponding benzylic alcohols. 3,3‐Diaryltetrahydrofurans, 4,4‐diaryltetrahydropyrans, 3,3‐diarylpyrrolidines, 4,4‐diaryl‐piperidines, as well as diarylcyclobutanes are examined, with results for 3,3‐diaryloxetanes and 3,3‐diarylazetidines presented for comparison. Three catalytic systems are investigated for each substrate [Ca(II), Li(I) and Fe(III)], across preinstalled aromatic groups of differing electronic character. In most cases examined, the diaryl product is obtained directly from the alcohol with good yields using the most appropriate catalyst system. In the absence of a nucleophile, the olefins from the 5‐ and 6‐membered substrates by elimination of water are obtained under the same reaction conditions. [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
View/download PDF

16. Synthesis of Novel Hydroxymethyl-Substituted Fused Heterocycles

Author

Holmes, Jane, primary, McGuire, Thomas, primary, Almeida, Lynsie, additional, Barlaam, Bernard, additional, Croft, Rosemary, additional, Dishington, Allan, additional, Gingipalli, Laksmaiah, additional, Hassall, Lorraine, additional, Hawkins, Janet, additional, Ioannidis, Stephanos, additional, Johannes, Jeffrey, additional, Moore, Jane, additional, Patel, Anil, additional, Pike, Kurt, additional, Pontz, Timothy, additional, Wu, Xiaoyun, additional, Wang, Tao, additional, Zhang, Hai-Jun, additional, and Zheng, Xiaolan, additional

Published
2016
Full Text
View/download PDF

20. Lithium-Catalyzed Thiol Alkylation with Tertiary and Secondary Alcohols: Synthesis of 3-Sulfanyl-Oxetanes as Bioisosteres.

Author

Croft, Rosemary A., Mousseau, James J., Chulho Choi, and Bull, James A.

Subjects
*ALKYLATION, *LITHIUM, *ALCOHOL, *ELECTRIC properties of metals, *BIOISOSTERES, *SULFIDES
Abstract

3-Sulfanyl-oxetanes are presented as promising novel bioisosteric replacements for thioesters or benzyl sulfides. From oxetan-3-ols, a mild and inexpensive Li catalyst enables chemoselective C@OH activation and thiol alkylation. Oxetane sulfides are formed from various thiols providing novel motifs in new chemical space and specifically as bioisosteres for thioesters due to their similar shape and electronic properties. Under the same conditions, various p-activated secondary and tertiary alcohols are also successful. Derivatization of the oxetane sulfide linker provides further novel oxetane classes and building blocks. Comparisons of key physicochemical properties of the oxetane compounds to selected carbonyl and methylene analogues indicate that these motifs are suitable for incorporation into drug discovery efforts. [ABSTRACT FROM AUTHOR]

Published
2018
Full Text
View/download PDF

21. Pyrimidinone Nicotinamide Mimetics as Selective Tankyrase and Wnt Pathway Inhibitors Suitable for in Vivo Pharmacology

Author

Johannes, Jeffrey W., primary, Almeida, Lynsie, additional, Barlaam, Bernard, additional, Boriack-Sjodin, P. Ann, additional, Casella, Robert, additional, Croft, Rosemary A., additional, Dishington, Allan P., additional, Gingipalli, Lakshmaiah, additional, Gu, Chungang, additional, Hawkins, Janet L., additional, Holmes, Jane L., additional, Howard, Tina, additional, Huang, Jian, additional, Ioannidis, Stephanos, additional, Kazmirski, Steven, additional, Lamb, Michelle L., additional, McGuire, Thomas M., additional, Moore, Jane E., additional, Ogg, Derek, additional, Patel, Anil, additional, Pike, Kurt G., additional, Pontz, Timothy, additional, Robb, Graeme R., additional, Su, Nancy, additional, Wang, Haiyun, additional, Wu, Xiaoyun, additional, Zhang, Hai-Jun, additional, Zhang, Yue, additional, Zheng, Xiaolan, additional, and Wang, Tao, additional

Published
2015
Full Text
View/download PDF

23. 2-Sulfinyl Oxetanes: Synthesis, Stability and Reactivity.

Author

Morgan, Kate F., Doran, Robert, Croft, Rosemary A., Hollingsworth, Ian A., and Bull, James A.

Subjects
SULFINYL compounds, CHEMICAL synthesis, CHEMICAL bonds, AROMATIC compounds, LIGAND exchange reactions
Abstract

The synthesis of 2-sulfinyl oxetanes is described by a C-C bond-forming cyclisation strategy. Oxetanes bearing electron-poor aryl sulfoxides are shown to be viable targets using this strategy. We report investigations into the sulfoxide magnesium exchange on 2-sulfinyl oxetanes, which resulted in products formed via ligand exchange and ligand coupling pathways. The sulfinyl oxetanes can be readily oxidised to the sulfonyl oxetanes. [ABSTRACT FROM AUTHOR]

Published
2016
Full Text
View/download PDF

26. Structurally Divergent Lithium Catalyzed Friedel-Crafts Reactions on Oxetan-3-ols: Synthesis of 3,3-Diaryloxetanes and 2,3-Dihydrobenzofurans.

Author

Croft RA, Mousseau JJ, Choi C, and Bull JA

Abstract

The first examples of 3,3-diaryloxetanes are prepared in a lithium-catalyzed and substrate dependent divergent Friedel-Crafts reaction. para-Selective Friedel-Crafts reactions of phenols using oxetan-3-ols afford 3,3-diaryloxetanes by displacement of the hydroxy group. These constitute new isosteres for benzophenones and diarylmethanes. Conversely, ortho-selective Friedel-Crafts reactions of phenols afford 3-aryl-3-hydroxymethyl-dihydrobenzofurans by tandem alkylation-ring-opening reactions; the outcome of the reaction diverging to structurally distinct products dependent on the substrate regioselectivity. Further reactivity of the oxetane products is demonstrated, suitable for incorporation into drug discovery efforts., (© 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Published
2016
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results