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Open AccessArticle

Anomeric Spironucleosides of β-d-Glucopyranosyl Uracil as Potential Inhibitors of Glycogen Phosphorylase

1
Organic Chemistry Laboratory, Department of Chemistry, National and Kapodistrian University of Athens, 10571 Athens, Greece
2
Institute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, Greece
*
Author to whom correspondence should be addressed.
Molecules 2019, 24(12), 2327; https://doi.org/10.3390/molecules24122327
Received: 13 May 2019 / Revised: 14 June 2019 / Accepted: 17 June 2019 / Published: 25 June 2019
(This article belongs to the Special Issue Biomimetic Radical Chemistry and Applications)
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Abstract

In the case of type 2 diabetes, inhibitors of glycogen phosphorylase (GP) may prevent unwanted glycogenolysis under high glucose conditions and thus aim at the reduction of excessive glucose production by the liver. Anomeric spironucleosides, such as hydantocidin, present a rich synthetic chemistry and important biological function (e.g., inhibition of GP). For this study, the Suárez radical methodology was successfully applied to synthesize the first example of a 1,6-dioxa-4-azaspiro[4.5]decane system, not previously constructed via a radical pathway, starting from 6-hydroxymethyl-β-d-glucopyranosyluracil. It was shown that, in the rigid pyranosyl conformation, the required [1,5]-radical translocation was a minor process. The stereochemistry of the spirocycles obtained was unequivocally determined based on the chemical shifts of key sugar protons in the 1H-NMR spectra. The two spirocycles were found to be modest inhibitors of RMGPb. View Full-Text
Keywords: type 2 diabetes; glycogen phosphorylase; anomeric spironucleosides; 1,6-dioxa-4-azaspiro[4.5]decane; [1,5]-radical translocation type 2 diabetes; glycogen phosphorylase; anomeric spironucleosides; 1,6-dioxa-4-azaspiro[4.5]decane; [1,5]-radical translocation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Stathi, A.; Mamais, M.; Chrysina, E.D.; Gimisis, T. Anomeric Spironucleosides of β-d-Glucopyranosyl Uracil as Potential Inhibitors of Glycogen Phosphorylase. Molecules 2019, 24, 2327.

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