A facile synthesis of 6-deoxydapagliflozin
A facile synthesis of a potent SGLT2 inhibitor, 6-deoxydapagliflozin, from methyl 2,3,4-tri- O -benzyl-6-deoxy-6-iodo- α - d -glucopyranoside in six steps with an overall yield of 50 % is described. The key steps were the reductive deiodination of the starting iodide under hydrogenolytic conditions...
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Published in | Monatshefte für Chemie Vol. 144; no. 12; pp. 1903 - 1910 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Vienna
Springer Vienna
01.12.2013
Springer Nature |
Subjects | |
Online Access | Get full text |
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Summary: | A facile synthesis of a potent SGLT2 inhibitor, 6-deoxydapagliflozin, from methyl 2,3,4-tri-
O
-benzyl-6-deoxy-6-iodo-
α
-
d
-glucopyranoside in six steps with an overall yield of 50 % is described. The key steps were the reductive deiodination of the starting iodide under hydrogenolytic conditions to build the desired 6-deoxyglucose functionality, the coupling of 2,3,4-tri-
O
-benzyl-6-deoxy-
d
-gluconolactone and (5-bromo-2-chlorophenyl)(4-ethoxyphenyl)methane, followed by BF
3
·Et
2
O-mediated reduction with Et
3
SiH in order to construct the desired anomeric β-configuration. A variety of methods used for the cleavage of benzyl groups in 2,3,4-tri-
O
-benzyl-1-[4-chloro-3-(4-ethoxybenzyl)phenyl]-1,6-dideoxy-
β
-
d
-glucopyranose were intensively screened, leading to the discovery of AlCl
3
-mediated cleavage as the optimal method.
Graphical Abstract
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ISSN: | 0026-9247 1434-4475 |
DOI: | 10.1007/s00706-013-1053-0 |