We report the syntheses and neuroprotective activities of hericenes and their derivatives against endoplasmic reticulum (ER) stress-dependent cell death. Four natural products, including hericenes A−C and hericenol A, and five synthetic derivatives were synthesized and their protective activities were evaluated. In designing the synthetic derivatives, we focused on the binding position of the fatty chain. Hericenes B and C showed moderate protective activity against thapsigargin-induced ER stress-dependent cell death. In contrast, their regioisomers (with respect to the position of the fatty chain) exhibited higher protective activity against tunicamycin-induced ER stress. This study clearly shows that the number and the binding position of the fatty chain are critical for protective activity against ER stress-dependent cell death.

我们报告了hericenes及其衍生物对内质网（ER）应力依赖性细胞死亡的合成和神经保护活性。合成了四种天然产物，包括Hericenes A-C和Hericenol A，以及五种合成衍生物，并评估了它们的保护活性。在设计合成衍生物时，我们集中于脂肪链的结合位置。Hericenes B和C对毒胡萝卜素诱导的ER应激依赖性细胞死亡具有中等程度的保护作用。相反，它们的区域异构体（相对于脂肪链的位置）表现出更高的针对衣霉素诱导的内质网应激的保护活性。这项研究清楚地表明，脂肪链的数量和结合位置对于抵抗内质网应激依赖性细胞死亡的保护活性至关重要。