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Cover Feature: Fluorine‐Directed Glycosylation Enables the Stereocontrolled Synthesis of Selective SGLT2 Inhibitors for Type II Diabetes (Chem. Eur. J. 12/2018)
Author(s) -
Sadurní Anna,
Kehr Gerald,
Ahlqvist Marie,
Wernevik Johan,
Sjögren Helena Peilot,
Kankkonen Cecilia,
Knerr Laurent,
Gilmour Ryan
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201800108
Subject(s) - chemistry , glycosylation , fluorine , transporter , selectivity , transmembrane protein , stereochemistry , biochemistry , combinatorial chemistry , receptor , gene , organic chemistry , catalysis
The Type II sodium–glucose co‐transporter (SGLT2, grey), located in the proximal tubule (gold) consists of a large transmembrane protein and is responsible for reabsorbing 90 % of the glucose that would naturally be excreted in urine. This study describes the effect of OH to F bioisosterism in representative SGLT2 inhibitors based on the β‐Phlorizin scaffold for the treatment of type 2 diabetes. We have shown that the introduction of fluorine at C2 is a powerful strategy to modulate glycosylation selectivity and override substrate‐based stereocontrol to favour formation of the 1,2‐ trans (β) linkage. More information can be found in the Communication by L. Knerr, R. Gilmour et al. on page 2832.