Chinese Journal of Organic Chemistry >
A Facile Convergent Synthetic Procedure for 3-Deoxydapagliflozin as SGLT2 Inhibitor
Received date: 2014-04-03
Revised date: 2014-05-06
Online published: 2014-05-07
Supported by
Project supported by the National Natural Science Foundation of China (No. 21302141), the Key Projects of Tianjin Science and Technology Support Plan (No. 10ZCKFSH01300) and the Tianjin Municipal Natural Science Foundation (No. 14JCQNJC12900).
3-Deoxydapagliflzoin (1) is a highly selective, potent sodium-dependent glucose transporter 2 (SGLT2) inhibitor discovered earlier. A facile convergent synthetic procedure for 3-deoxydapagliflzoin (1) was developed in 13 steps and in 38% overall yield starting from inexpensive methyl α-D-glucopyranoside 2. Regioselective protection of 2-OH and 3-OH in the key intermediate methyl 4,6-O-benzylidene-α-D-glucopyranoside 3 was systematically studied; the regioisomers thus obtained were distinguished from each other with nuclear overhauser effect (NOE) and their ratios and relative polarities were rationally explained. The strategy for deoxygenation of the sterically hindered 3-OH in another key intermediate 4,6-O-benzylidene-2-O-t-butyldiphenylsilyl-α-D-glucopyranoside (4) was also systematically studied. The facile synthetic route is characterized by convergence characteristics and inexpensive starting material, also representing an alternative general synthetic approach to phenyl 3-deoxy-C-glucosides.
Gao Zhigang , Zhang Datong , Wei Peng , Wang Zhe , Xie Yafei , Liu Yuqiang , Xu Weiren , Tang Lida , Zhao Guilong . A Facile Convergent Synthetic Procedure for 3-Deoxydapagliflozin as SGLT2 Inhibitor[J]. Chinese Journal of Organic Chemistry, 2014 , 34(9) : 1829 -1839 . DOI: 10.6023/cjoc21404007
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