Regio- and Diastereoselective Construction of α‑Hydroxy-δ-amino Ester Derivatives via 1,4-Conjugate Addition of β,γ-Unsaturated <i>N</i>‑Sulfonylimines

A first example of 1,4-conjugate addition of β,γ-unsaturated N-sulfonylimines via the oxonium ylides trapping process was developed. This method afforded a novel and efficient access for the high regio- and diastereoselective construction of α-hydroxyl-δ-amino esters derivatives, which exhibit inhibitory activity on PTP1B and SIRT1 enzymes in vitro. The synthetic potentials and the biological activity of the resulting products were well demonstrated to be promising for drug discovery.本研究开发了首例通过氧鎓叶立德捕获过程实现的β,γ-不饱和N-磺酰亚胺1,4-共轭加成反应。该方法为高区域选择性与非对映选择性构建α-羟基-δ-氨基酯衍生物提供了新颖高效的途径，此类衍生物在体外对蛋白酪氨酸磷酸酶1B（PTP1B）及沉默信息调节因子1（SIRT1）两种酶均具有抑制活性。所得产物的合成应用价值与生物活性均得到充分验证，表明其在药物研发领域具备良好的应用前景。