The Experts below are selected from a list of 18 Experts worldwide ranked by ideXlab platform
Graham Pattison - One of the best experts on this subject based on the ideXlab platform.
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effects of replacing Oxygenated Functionality with fluorine on lipophilicity
Journal of Medicinal Chemistry, 2021Co-Authors: Richard J Glyn, Graham PattisonAbstract:The replacement of Oxygenated Functionality (hydroxy and alkoxy) with a fluorine atom is a commonly used bioisosteric replacement in medicinal chemistry. In this paper, we use molecular matched-pair analysis to better understand the effects of this replacement on lipophilicity. It seems that the reduced log P of the Oxygenated compound is normally dominant in determining the size of this difference. We observe that the presence of additional electron-donating groups on an aromatic ring generally increases the difference in lipophilicity between an Oxygenated compound and its fluorinated analogue, while electron-withdrawing groups lead to smaller differences. Ortho-substituted compounds generally display a reduced difference in log P compared to para- and meta-substituted compounds, particularly if an ortho-substituent can form an intramolecular hydrogen bond. Hydrogen-bond acceptors remote to an aromatic ring containing fluorine/oxygen can also reduce the difference in log P between oxygen- and fluorine-substituted compounds.
Richard J Glyn - One of the best experts on this subject based on the ideXlab platform.
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effects of replacing Oxygenated Functionality with fluorine on lipophilicity
Journal of Medicinal Chemistry, 2021Co-Authors: Richard J Glyn, Graham PattisonAbstract:The replacement of Oxygenated Functionality (hydroxy and alkoxy) with a fluorine atom is a commonly used bioisosteric replacement in medicinal chemistry. In this paper, we use molecular matched-pair analysis to better understand the effects of this replacement on lipophilicity. It seems that the reduced log P of the Oxygenated compound is normally dominant in determining the size of this difference. We observe that the presence of additional electron-donating groups on an aromatic ring generally increases the difference in lipophilicity between an Oxygenated compound and its fluorinated analogue, while electron-withdrawing groups lead to smaller differences. Ortho-substituted compounds generally display a reduced difference in log P compared to para- and meta-substituted compounds, particularly if an ortho-substituent can form an intramolecular hydrogen bond. Hydrogen-bond acceptors remote to an aromatic ring containing fluorine/oxygen can also reduce the difference in log P between oxygen- and fluorine-substituted compounds.
Rajib Kumar Goswami - One of the best experts on this subject based on the ideXlab platform.
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Total Synthesis of Cytospolide Q
2018Co-Authors: Shamba Chatterjee, Gour Hari Mandal, Rajib Kumar GoswamiAbstract:A flexible and convergent strategy for the stereoselective total synthesis of bioactive marine natural product cytospolide Q has been developed. The key features of this synthesis include Evans anti-aldol reaction for the installation of C-2 and C-3 stereocenters and cycloetherification via epoxide opening followed by concomitant lactonization for the construction of tetrahydrofuran and γ-butyrolactone scaffolds. This synthetic study also revealed that protected Oxygenated Functionality (methyl ester or benzyl ether) at C-1 position participated readily in epoxide opening
Wilkes Antonia - One of the best experts on this subject based on the ideXlab platform.
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Towards the synthesis of the ABC tricycle of Taxol
2015Co-Authors: Wilkes AntoniaAbstract:Taxol is one of the world’s most successful drugs used in the treatment of cancers. Isolated from the bark of the Pacific yew tree (Taxus brevifolia), it is a molecule of great interest within organic chemistry; with six total syntheses and a number of synthetic works having been published since its discovery. A semi-convergent synthesis of an intermediate in Holton’s synthesis was planned. The overall synthetic plan is shown below. The A ring would be installed by an intramolecular pinacol condensation. The BC bicycle would be closed by ring-closing metathesis at C10-C11. The ketone at C12 would be protected as an alkyne and the BC bicycle precursor would be obtained by coupling fragment A and the C ring. This thesis describes the preparation of a model C ring, without the Oxygenated Functionality at C7, was successfully synthesised along with fragment A. Metathesis precursors were synthesised and gold hydration reactions were attempted
Shamba Chatterjee - One of the best experts on this subject based on the ideXlab platform.
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Total Synthesis of Cytospolide Q
2018Co-Authors: Shamba Chatterjee, Gour Hari Mandal, Rajib Kumar GoswamiAbstract:A flexible and convergent strategy for the stereoselective total synthesis of bioactive marine natural product cytospolide Q has been developed. The key features of this synthesis include Evans anti-aldol reaction for the installation of C-2 and C-3 stereocenters and cycloetherification via epoxide opening followed by concomitant lactonization for the construction of tetrahydrofuran and γ-butyrolactone scaffolds. This synthetic study also revealed that protected Oxygenated Functionality (methyl ester or benzyl ether) at C-1 position participated readily in epoxide opening
