A Facile Convergent Synthetic Procedure for 3-Deoxydapagliflozin as SGLT2 Inhibitor

doi:10.6023/cjoc21404007

Chin. J. Org. Chem. ›› 2014, Vol. 34 ›› Issue (9): 1829-1839.DOI: 10.6023/cjoc21404007 Previous Articles Next Articles

SGLT2抑制剂3-脱氧达格列净简便的汇聚式合成方法

高志刚^a, 张大同^a, 魏鹏^a, 王哲^c, 谢亚非^b, 刘钰强^b, 徐为人^b, 汤立达^b, 赵桂龙^a,b

a 齐鲁工业大学化学与制药工程学院, 济南 250353;
b 天津药物研究院天津市新药设计与发现重点实验室, 天津 300193;
c 山东中医药大学第一临床医学院, 济南 250014

收稿日期:2014-04-03 修回日期:2014-05-06 发布日期:2014-05-07
通讯作者: 张大同, 赵桂龙 E-mail:zhao_guilong@126.com; datong_zhang@163.com
基金资助:
国家自然科学基金(No. 21302141)、天津市科技支撑计划重点项目(No. 10ZCKFSH01300)和天津市自然科学基金(No. 14JCQNJC12900)资助项目.

A Facile Convergent Synthetic Procedure for 3-Deoxydapagliflozin as SGLT2 Inhibitor

Gao Zhigang^a, Zhang Datong^a, Wei Peng^a, Wang Zhe^c, Xie Yafei^b, Liu Yuqiang^b, Xu Weiren^b, Tang Lida^b, Zhao Guilong^a,b

a School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology, Jinan 250353;
b Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193;
c First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250014

Received:2014-04-03 Revised:2014-05-06 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).

1. A Facile Convergent Synthetic Procedure for 3-Deoxydapagliflozin as SGLT2 Inhibitor.PDF(1188KB)

Abstract

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.

Key words: SGLT2 inhibitor, 3-deoxydapagliflozin, regioselectivity, deoxygenation, convergent synthesis

Cite this article

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]. Chin. J. Org. Chem., 2014, 34(9): 1829-1839.

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SGLT2抑制剂3-脱氧达格列净简便的汇聚式合成方法

A Facile Convergent Synthetic Procedure for 3-Deoxydapagliflozin as SGLT2 Inhibitor

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