摘要
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 alpha-D-glucopyranoside 2. Regioselective protection of 2-OH and 3-OH in the key intermediate methyl 4,6-O-benzylidene-alpha-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-alpha-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.
- 出版日期2014-9
- 单位天津药物研究院有限公司; 山东中医药大学