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
In the case of type 2 diabetes, inhibitors of glycogen phosphorylase (GP) might 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. Herein, the Suárez radical methodology is successfully applied 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-b-D-glucopyranosyluracil. It is shown that in the rigid pyranosyl conformation the required [1,5]-radical translocation is 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.
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.