GLUT_1介导的脑靶向去甲文拉法辛前药的设计与合成

Design and synthesis of GLUT_1 mediated brain targeting prodrug of desvenlafaxine

目的合成一种由葡萄糖转运蛋白1(GLUT1)介导的脑靶向去甲文拉法辛前药。方法将苄基保护的去甲文拉法辛与己二酸单叔丁酯在缩合剂DCC作用下成酯Ⅱ,经三氟乙酸脱除叔丁基保护后,再与1,2,3,4-四-O-三甲硅基-α-D-吡喃葡萄糖在缩合剂DCC的作用下成酯,在酸性条件下脱除三甲硅基保护,最后催化氢化脱除苄基保护得到目标化合物。结果与结论合成了目标化合物脑靶向去甲文拉法辛前药;目标化合物及重要中间体均经1HNMR和MS确证。

OBJECTIVE To synthesize a brain targeting prodrug of desvenlafaxine mediated by glucose transporter 1（GLUT1）.METHODS Desvenlafaxine protected by benzyl group was coupled with mono t-butyl adipic acid to afford compound Ⅱ,which was deprotected by trifluoroacetic acid to afford acid Ⅲ.Then compound Ⅲ was coupled with 1,2,3,4-tetra-O-trimethylsilyl-α-D-glucopyranose in the presence of DCC and DMAP to get compound Ⅳ,which was deprotected by acid to obtain compound Ⅴ.Deprotection of compound Ⅴ by H2/Pd furnished the target compound Ⅵ.RESULTS and CONCLUSION The target compound was successfully synthesized.The chemical structure of the target compound and intermediates were characterized by 1HNMR and MS.