Version 1
: Received: 14 May 2019 / Approved: 15 May 2019 / Online: 15 May 2019 (12:21:50 CEST)
Version 2
: Received: 17 June 2019 / Approved: 18 June 2019 / Online: 18 June 2019 (10:26:30 CEST)
Stathi, A.; Mamais, M.; Chrysina, E.D.; Gimisis, T. Anomeric Spironucleosides of β-d-Glucopyranosyl Uracil as Potential Inhibitors of Glycogen Phosphorylase. Molecules2019, 24, 2327.
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.
Stathi, A.; Mamais, M.; Chrysina, E.D.; Gimisis, T. Anomeric Spironucleosides of β-d-Glucopyranosyl Uracil as Potential Inhibitors of Glycogen Phosphorylase. Molecules2019, 24, 2327.
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.
Abstract
Glycogen phosphorylase (GP) has been a target for compounds, inhibitors of GP that might prevent unwanted glycogenolysis under high glucose conditions and thus aim at the reduction of excessive glucose production from the liver, in the case of type 2 diabetes. Anomeric spironucleosides, such as hydantocidin, present a rich synthetic chemistry and possess important biological function. We have successfully applied the Suárez radical methodology to synthesize the first example of a 1,6-dioxa-4-azaspiro[4.5]decane system, not been previously constructed via a radical pathway, starting from 6-hydroxymethyl-β-D-glucopyranosyluracil. We have shown that in the rigid pyranosyl conformation the required [1,5]-radical translocation is a minor process. The stereochemistry of the spirocycles obtained were 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.
Keywords
Type 2 diabetes; glycogen phosphorylase; anomeric spironucleosides; 1,6-dioxa-4-azaspiro[4.5]decane; [1,5]-radical translocation
Subject
Chemistry and Materials Science, Organic Chemistry
Copyright:
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.
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