海洋甾体(25R)-胆甾-3β,5α,6β,26-四醇的合成及生物活性研究

Synthesis and Bioactivities of Marine Sterol(25R)-Cholest-3β,5α,6β,26-Tetrol

目的设计合成天然产物(25R)-胆甾-3β,5α,6β,26-四醇,并评价其抗胶质瘤活性。方法以薯蓣皂素为原料,经过Zn-Hg齐还原开环,叔丁基二甲基氯硅烷(TBDMSCl)保护C-3、C-26羟基,甲基磺酰氯(MsCl)磺酰酯化C-16羟基,LiAlH4还原C-16甲基磺酸酯,间氯过氧苯甲酸(mCPBA)氧化5,6位双键,酸性条件下开环、脱保护反应得到(25R)-胆甾-3β,5α,6β,26-四醇;并通过MTT法对该化合物的抗胶质瘤活性进行了初步研究。结果各中间体和目标化合物通过1H-NMR、13C-NMR、IR、EI-MS、EA等现代波谱技术进行了结构表征;化合物在浓度为10～150μg.mL-1时,胶质瘤细胞的生存率存在显著性差异,其IC50为51.57μg.mL-1。结论利用廉价易得的薯蓣皂素合成了一种天然海洋甾体,该目标化合物具有显著的抗胶质瘤活性,且具有浓度依赖性,值得进一步研究。

OBJECTIVE To synthesize a marine sterol（25R）-cholestane-3β,5α,6β,26-tetrol and to investigate its anti-glioma activity.METHODS Starting from commercially available diosgenin,（25R）-5α-cholest-5-en-3β,16β,26-triol was first synthesized by reduction with Zn amalgam;then（25R）-3,26-di（t-butyldimethylsilyloxy）-5α-cholest-5-en-3β,26-diol was synthesized by protection with TBDMSCl,methyl sulfonylation with MsCl and elimination with LiAlH4;finally,the aimed compound was obtained by oxidation of mCPBA and hydroxylation.Its anti-glioma activity was investigated by MTT method.RESULTS The aimed compound and its intermediates were characterized by 1H-NMR,13C-NMR spectra,IR EI-MS and EA.The effective inhibiting concentrations ranges were 10-150 μg·mL-1,and the IC50 was 51.57 μg·mL-1.CONCLUSION The study has established a synthetic method for marine sterol which can significantly suppress the growth of MGR2 malignant glioma cells in a concentration-dependent manner.