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

Stathi, Aggeliki; Mamais, Michael; Chrysina, Evangelia D.; Gimisis, Thanasis

doi:10.3390/molecules24122327

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

Aggeliki Stathi

¹,

Michael Mamais

^1,2

Evangelia D. Chrysina

² and

Thanasis Gimisis

^1,*

Organic Chemistry Laboratory, Department of Chemistry, National and Kapodistrian University of Athens, 10571 Athens, Greece

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

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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. https://doi.org/10.3390/molecules24122327

AMA Style

Stathi A, Mamais M, Chrysina ED, Gimisis T. Anomeric Spironucleosides of β-d-Glucopyranosyl Uracil as Potential Inhibitors of Glycogen Phosphorylase. Molecules. 2019; 24(12):2327. https://doi.org/10.3390/molecules24122327

Chicago/Turabian Style

Stathi, Aggeliki, Michael Mamais, Evangelia D. Chrysina, and Thanasis Gimisis. 2019. "Anomeric Spironucleosides of β-d-Glucopyranosyl Uracil as Potential Inhibitors of Glycogen Phosphorylase" Molecules 24, no. 12: 2327. https://doi.org/10.3390/molecules24122327

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

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