In pursuit of larger lipophilicity enhancement: an investigation of sugar deoxychlorination
In pursuit of larger lipophilicity enhancement: an investigation of sugar deoxychlorination
The excessive hydrophilicity of carbohydrates hampers their application in drug discovery. Deoxyfluorination is one of the strategies to increase sugar lipophilicity. However, lipophilicities of dideoxy-difluorinated monosaccharides are still well below the desired range for oral drug candidates. Here we investigate the power of deoxychlorination to increase sugar lipophilicities. A
series of dideoxygenated chloro-fluorosugars was synthesized and for these substrates it was shown that deoxychlorination increased the logP with an average of 1.37 logP units, compared to 0.83 logP units for analogous deoxyfluorination. This shows the potential of deoxychlorination of carbohydrates to increase lipophilicity while limiting the number of potentially important hydrogen bond donating groups to be sacrificed, and will be of interest for glycomimetic development.
2586-2589
Van De Velde, Jonas
cb2e4bb4-56eb-415c-83d4-7b3cdc28a792
Calderón Rodríguez, Ariadna
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Wang, Zhong
fe914552-33f1-4f0a-b8a1-52b82e8cb89e
Wheatley, David E.
259931a5-d5a7-4400-80c9-2a7e8d161a74
Linclau, Bruno
19b9cacd-b8e8-4c65-af36-6352cade84ba
21 March 2025
Van De Velde, Jonas
cb2e4bb4-56eb-415c-83d4-7b3cdc28a792
Calderón Rodríguez, Ariadna
da42b12d-0c5f-4751-ac87-0234bf81e133
Wang, Zhong
fe914552-33f1-4f0a-b8a1-52b82e8cb89e
Wheatley, David E.
259931a5-d5a7-4400-80c9-2a7e8d161a74
Linclau, Bruno
19b9cacd-b8e8-4c65-af36-6352cade84ba
Van De Velde, Jonas, Calderón Rodríguez, Ariadna, Wang, Zhong, Wheatley, David E. and Linclau, Bruno
(2025)
In pursuit of larger lipophilicity enhancement: an investigation of sugar deoxychlorination.
Organic & Biomolecular Chemistry, 23 (11), .
(doi:10.1039/D5OB00037H).
Abstract
The excessive hydrophilicity of carbohydrates hampers their application in drug discovery. Deoxyfluorination is one of the strategies to increase sugar lipophilicity. However, lipophilicities of dideoxy-difluorinated monosaccharides are still well below the desired range for oral drug candidates. Here we investigate the power of deoxychlorination to increase sugar lipophilicities. A
series of dideoxygenated chloro-fluorosugars was synthesized and for these substrates it was shown that deoxychlorination increased the logP with an average of 1.37 logP units, compared to 0.83 logP units for analogous deoxyfluorination. This shows the potential of deoxychlorination of carbohydrates to increase lipophilicity while limiting the number of potentially important hydrogen bond donating groups to be sacrificed, and will be of interest for glycomimetic development.
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D5OB00037H
- Accepted Manuscript
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d5ob00037h
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Accepted/In Press date: 4 February 2025
e-pub ahead of print date: 5 February 2025
Published date: 21 March 2025
Identifiers
Local EPrints ID: 498795
URI: http://eprints.soton.ac.uk/id/eprint/498795
ISSN: 1477-0520
PURE UUID: dd6de540-0896-48f9-8d10-f5ca543d698e
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Date deposited: 28 Feb 2025 17:34
Last modified: 22 Aug 2025 01:46
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Contributors
Author:
Jonas Van De Velde
Author:
Ariadna Calderón Rodríguez
Author:
David E. Wheatley
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