A facile synthesis of 6-deoxydapagliflozin

• Published in: Monatshefte für Chemie Vol. 144; no. 12; pp. 1903 - 1910
• Main Authors: Shi, Yongheng, Xu, Huaqiang, Liu, Bingni, Kong, Weiling, Wei, Qunchao, Xu, Weiren, Tang, Lida, Zhao, Guilong
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.12.2013; Springer Nature
• Subjects: Analytical Chemistry; Chemistry; Chemistry and Materials Science; Chemistry, Multidisciplinary; Chemistry/Food Science; Inorganic Chemistry; Organic Chemistry; Original Paper; Physical Chemistry; Physical Sciences; Science & Technology; Theoretical and Computational Chemistry; Carbohydrates; Drug research; Hydrogenolysis; Dapagliflozin; SGLT2 inhibitor; ALCOHOLS; GLUCOSIDE SGLT2 INHIBITORS; ANALOGS
• ISSN: 0026-9247; 1434-4475
• DOI: 10.1007/s00706-013-1053-0

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 .