Mi Yang, Ren Yu-Hao, Li Ying, Zhang Ren-Chao, Zhao Jin-Xin, Zhou Bin, Yue Jian-Min
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, 222 South Tianshui Road, Lanzhou, Gansu 730000, People's Republic of China.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, People's Republic of China.
J Org Chem. 2025 Apr 4;90(13):4714-4724. doi: 10.1021/acs.joc.5c00211. Epub 2025 Mar 20.
Steroids have consistently drawn scientific attention due to their diverse structures and exceptional pharmacological activities. However, halogenated natural steroids remain relatively rare, especially for those derived from plants. In this study, two chlorinated C steroids hocarnoids A () and B () were identified from the folk medicinal plant , representing the first examples of plant derived C-16 chlorinated steroids. Semisynthesis of compounds and was completed in 4 and 5 linear steps with 28.2% and 25.3% overall yields through a modified approach, corroborating further their structures. A total collection of 11 C steroids, including intermediates obtained during the synthesis, were evaluated for the anti-inflammatory activity against lipopolysaccharide (LPS)-induced inflammation-related RAW 264.7 macrophages. Among them, the natural product hocarnoid A () displayed the strongest anti-inflammatory activity with an IC value of 3.62 ± 0.08 μM, which also attenuated the mRNA levels of proinflammatory cytokines IL-1β, IL-6, IL-10, and TNF-α.
甾体化合物因其多样的结构和卓越的药理活性一直备受科学界关注。然而，卤代天然甾体化合物仍然相对稀少，尤其是那些源自植物的。在本研究中，从民间药用植物中鉴定出两种氯化C甾体类化合物霍卡诺德A（）和B（），它们是植物来源的C-16氯化甾体化合物的首例。通过一种改进方法，化合物和的半合成以4步和5步线性反应完成，总产率分别为28.2%和25.3%，进一步证实了它们的结构。总共收集了11种C甾体化合物，包括合成过程中得到的中间体，对其针对脂多糖（LPS）诱导的炎症相关RAW 264.7巨噬细胞的抗炎活性进行了评估。其中，天然产物霍卡诺德A（）表现出最强的抗炎活性，IC值为3.62±0.08μM，它还降低了促炎细胞因子IL-1β、IL-
