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


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   

  1. 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;
  • 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 Zhiganga, Zhang Datonga, Wei Penga, Wang Zhec, Xie Yafeib, Liu Yuqiangb, Xu Weirenb, Tang Lidab, Zhao Guilonga,b   

  1. 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).

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