Synthesis and Biological Studies of O3-Aryl Galactosides as Galectin Inhibitors
(2021) In Helvetica Chimica Acta 104(2).- Abstract
β-Galactose derivatives have recently been reported to selectively inhibit galectin-3, and a library of O3-arylated galactosides with varying substitution patterns was designed to study such inhibitions further. The O3-arylated galactosides were synthesized using diaryliodonium salts under mild and transition metal free conditions, providing the target products in moderate to good yields. An O3-trifluoroethylated galactoside was also synthesized using iodonium salt chemistry. Azido-substituted products were subsequently transformed into the corresponding triazoles. After deprotection, a selection of galactoside derivatives were evaluated for inhibitory potencies against galectins-1, 3, 4 N (N-terminal domain), 4 C (C-terminal domain),... (More)
β-Galactose derivatives have recently been reported to selectively inhibit galectin-3, and a library of O3-arylated galactosides with varying substitution patterns was designed to study such inhibitions further. The O3-arylated galactosides were synthesized using diaryliodonium salts under mild and transition metal free conditions, providing the target products in moderate to good yields. An O3-trifluoroethylated galactoside was also synthesized using iodonium salt chemistry. Azido-substituted products were subsequently transformed into the corresponding triazoles. After deprotection, a selection of galactoside derivatives were evaluated for inhibitory potencies against galectins-1, 3, 4 N (N-terminal domain), 4 C (C-terminal domain), 7, 8 N, 8 C, 9 N, and 9 C and one compound with promising affinity and selectivity for both the N- and C-terminal domain of galectin-9 was discovered.
(Less)
- author
- Kervefors, Gabriella ; Pal, Kumar Bhaskar ; Tolnai, Gergely L. ; Mahanti, Mukul LU ; Leffler, Hakon LU ; Nilsson, Ulf J. LU and Olofsson, Berit
- organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- arylation, carbohydrates, galactosides, galectin inhibitor, hypervalent compounds
- in
- Helvetica Chimica Acta
- volume
- 104
- issue
- 2
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- scopus:85100454987
- ISSN
- 0018-019X
- DOI
- 10.1002/hlca.202000220
- language
- English
- LU publication?
- yes
- id
- 598ce7d9-b4c5-42d0-a1f6-ca17f5d7c28e
- date added to LUP
- 2021-02-19 09:11:07
- date last changed
- 2022-04-27 00:22:18
@article{598ce7d9-b4c5-42d0-a1f6-ca17f5d7c28e,
abstract = {{<p>β-Galactose derivatives have recently been reported to selectively inhibit galectin-3, and a library of O3-arylated galactosides with varying substitution patterns was designed to study such inhibitions further. The O3-arylated galactosides were synthesized using diaryliodonium salts under mild and transition metal free conditions, providing the target products in moderate to good yields. An O3-trifluoroethylated galactoside was also synthesized using iodonium salt chemistry. Azido-substituted products were subsequently transformed into the corresponding triazoles. After deprotection, a selection of galactoside derivatives were evaluated for inhibitory potencies against galectins-1, 3, 4 N (N-terminal domain), 4 C (C-terminal domain), 7, 8 N, 8 C, 9 N, and 9 C and one compound with promising affinity and selectivity for both the N- and C-terminal domain of galectin-9 was discovered.</p>}},
author = {{Kervefors, Gabriella and Pal, Kumar Bhaskar and Tolnai, Gergely L. and Mahanti, Mukul and Leffler, Hakon and Nilsson, Ulf J. and Olofsson, Berit}},
issn = {{0018-019X}},
keywords = {{arylation; carbohydrates; galactosides; galectin inhibitor; hypervalent compounds}},
language = {{eng}},
number = {{2}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Helvetica Chimica Acta}},
title = {{Synthesis and Biological Studies of O3-Aryl Galactosides as Galectin Inhibitors}},
url = {{http://dx.doi.org/10.1002/hlca.202000220}},
doi = {{10.1002/hlca.202000220}},
volume = {{104}},
year = {{2021}},
}