Diastereoselective Synthesis of the Borylated d-Galactose Monosaccharide 3-Boronic-3-Deoxy-d-Galactose and Biological Evaluation in Glycosidase Inhibition and in Cancer for Boron Neutron Capture Therapy (BNCT)
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Published:2023-05-24
Issue:11
Volume:28
Page:4321
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ISSN:1420-3049
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Container-title:Molecules
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language:en
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Short-container-title:Molecules
Affiliation:
1. Discipline of Chemistry, University of Newcastle, Callaghan, NSW 2308, Australia 2. Newcastle CSIRO Energy Centre, 10 Murray Dwyer Circuit, Newcastle, NSW 2304, Australia
Abstract
Drug leads with a high Fsp3 index are more likely to possess desirable properties for progression in the drug development pipeline. This paper describes the development of an efficient two-step protocol to completely diastereoselectively access a diethanolamine (DEA) boronate ester derivative of monosaccharide d-galactose from the starting material 1,2:5,6-di-O-isopropylidene-α-d-glucofuranose. This intermediate, in turn, is used to access 3-boronic-3deoxy-d-galactose for boron neutron capture therapy (BNCT) applications. The hydroboration/borane trapping protocol was robustly optimized with BH3.THF in 1,4-dioxane, followed by in-situ conversion of the inorganic borane intermediate to the organic boron product by the addition of DEA. This second step occurs instantaneously, with the immediate formation of a white precipitate. This protocol allows expedited and greener access to a new class of BNCT agents with an Fsp3 index = 1 and a desirable toxicity profile. Furthermore, presented is the first detailed NMR analysis of the borylated free monosaccharide target compound during the processes of mutarotation and borarotation.
Funder
B18 Project Priority Research Centre for Drug Development Faculty of Science
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
Reference72 articles.
1. Campkin, D.M., Shimadate, Y., Bartholomew, B., Bernhardt, P.V., Nash, R.J., Sakoff, J.A., Kato, A., and Simone, M. (2022). Borylated 2,3,4,5-Tetrachlorophthalimide and Their 2,3,4,5-Tetrachlorobenzamide Analogues: Synthesis, Their Glycosidase Inhibition and Anticancer Properties in View to Boron Neutron Capture Therapy. Molecules, 27. 2. Garget, T.A., Houston, T.A., Kiefel, M.J., and Simone, M. (2022). Reference Module in Chemistry, Molecular Sciences and Chemical Engineering, Elsevier Inc. 3. Methyl 2-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-4-nitrobenzoate;Jenkinson;Acta Cryst.,2012 4. Borylated methyl cinnamates: Green synthesis, characterization, crystallographic analysis and biological activities—In glycosidase inhibition and in cancer cells lines;Legge;Beilstein Arch.,2021 5. Facile amidinations of 2-aminophenylboronic acid promoted by boronate ester formation;Pappin;Org. Biomol. Chem.,2019
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