Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals and College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.
Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals and College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.
Bioorg Chem. 2020 Nov;104:104281. doi: 10.1016/j.bioorg.2020.104281. Epub 2020 Sep 17.
A detailed chemical research of the soft coral Sinularia crassa collected from the South China Sea yielded a series of cembrane-type diterpenoids, including four new cembranoids, namely sinulacrassins A - C (1, (+)-2, (+)-4) and ent-xishaflavalin G ((+)-3), along with five known analogs ((-)-3, 5-8). Their structures were elucidated by detailed spectroscopic analysis, chemical methods, and the comparison with those literature data. The absolute configuration of 1 was established by time-dependent density functional theory electronic circular dichroism (TDDFT/ECD) calculation, and the absolute configuration of (+)-2 was determined using the modified Mosher's method. The bioassay results revealed that (+)-2 and 5 were novel α-glucosidase inhibitors with IC values of 10.65 ± 0.16 and 30.31 ± 1.22 μM, respectively. In addition, (+)-2 and 5 were nontoxic towards human normal hepatocyte (LO2) cells at 100 μM. The present results highlighted the unusual coexistence of α and β configurations of C-1 in cembranoids from soft coral in the Order Alcyonacea, and provided new chemotype for the development of α-glucosidase inhibitors used in anti-diabetes treatment.
从南海采集的软珊瑚 Sinularia crassa 进行了详细的化学研究，得到了一系列海鞘烷型二萜类化合物，包括四个新的海鞘烷类化合物，即 sinulacrassins A-C（1、(+)-2、(+)-4）和 ent-xishaflavalin G ((+)-3)，以及五个已知类似物 ((-)-3、5-8)。通过详细的光谱分析、化学方法以及与文献数据的比较，确定了它们的结构。通过时间依赖密度泛函理论电子圆二色性 (TDDFT/ECD) 计算确定了 1 的绝对构型，并用改良的 Mosher 法确定了 (+)-2 的绝对构型。生物测定结果表明，(+)-2 和 5 是新型的α-葡萄糖苷酶抑制剂，IC 值分别为 10.65±0.16 和 30.31±1.22μM。此外，(+)-2 和 5 在 100μM 时对人正常肝细胞 (LO2) 无毒性。本研究结果突出了软珊瑚在 Order Alcyonacea 中存在 C-1 的α和β构型的不寻常共存，并为开发用于抗糖尿病治疗的α-葡萄糖苷酶抑制剂提供了新的化学类型。
