HDAC6选择性抑制剂WT161的合成工艺优化

Optimization of Synthetic Process of HDAC6 Selective Inhibitor WT161

本文报道了一条新的合成HDAC6选择性抑制剂WT161的路线。以辛二酸单甲酯为起始原料,经缩合、取代、还原、脱水共四步反应得到HDAC6选择性抑制剂WT161,总收率64.8%,目标产物结构均经过~1HNMR、^(13)CNMR和HRMS等确证。优化后的工艺路线原料成本低、反应条件温和、反应后处理更简单、产物收率更高,比较适合较大规模制备。

A novel synthetic process of HDAC6 selective inhibitor WT161 has been developed. WT161 was synthesized from commercially available monomethyl suberate by four steps, namely condensation, substitution, reduction and dehydration, in 64.8% overall yield. The structure of the target product were confirmed by ^1H NMR, ^13CNMR and HRMS. The optimized synthetic route has the advantages of cost-effectiveness, mild conditions, easy chemical operation, high yield, and easy scale-up production.