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有机化学 ›› 2010, Vol. 30 ›› Issue (11): 1689-1694. 上一篇    下一篇

研究论文

6-羟基-3-硫酸酯钠甾体化合物的合成及生理活性研究

黄燕敏，李莹，崔建国*，王辉，范良华   

  1. (广西师范学院化学系 南宁 530001)
  • 收稿日期:2009-10-12 修回日期:2010-05-06 发布日期:2010-06-17
  • 通讯作者: 崔建国 E-mail:cuijg1954@126.com

Synthesis and Bioactivity of Sodium 3,6-Dihydroxy-5α-steroid- 3-sulfateds

HUANG Yan-Min, LI Ying, CUI Jian-Guo, WANG Hui, FAN Liang-Hua   

  1. (College of Chemistry and Life Science, Guangxi Teachers Education University, Nanning 530001)
  • Received:2009-10-12 Revised:2010-05-06 Published:2010-06-17

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1063

被引次数

11

甾醇硫酸酯钠化合物由于其独特的结构特征和特殊的生理活性正引起人们越来越多的关注. 从天然存在的甾醇1a～1b出发, 经过PCC氧化得到4-烯-3,6-二羰基甾体化合物2a～2b, 然后在Ni2＋存在的条件下用硼氢化钠还原2a～2b, 得到3-羟基-6-酮甾体化合物3a～3b. 利用三乙胺-三氧化硫复合物对3a～3b进行硫酸酯化得到4a～4b, 然后通过阳离子(钠型)交换树脂对4a～4b进行Na＋交换得到6-氧代-3β-硫酸酯钠盐5a～5b, 5a～5b进一步通过NaBH4还原得到6-羟基-3β-硫酸酯钠(6a～6b). 另外, 采用类似的方法合成了6-羟基胆甾-4-烯-3β-硫酸酯钠(10a). 并对化合物5a～5b和6a～6b进行抗肿瘤活性试验, 结果表明6a在体外对卵巢癌(Hey-1B)细胞株具有较好的细胞毒性, IC50值为48 nmol/mL.

关键词: 甾醇, 甾醇硫酸酯钠, 6-羟基-3β-硫酸酯钠甾体化合物, 合成

In recent years, the sodium polyhydroxysterols sulfated greatly attract the attention of organic chemists and biomedical scientists due to their novel structures and biological activities against cancer and micropathogens. Using natural sterols (1a～1b) as starting materials, sodium 3,6-dihydroxy-5α-sterol 3-sulfateds (6a～6b) were synthesized in 5 steps with a high overall yield. First, 1a～1b were transformed into the corresponding 4-ene-3,6-dione-steroids (2a～2b) via oxidation with pyridinium chlorochromate ( PCC ). The reduction of 2a～2b by NaBH4 in the presence of NiCl2 gave 3β-hydroxy-6-oxysteroids (3a～3b). The reaction of 3a～3b with triethylamine-sulfur trioxide complex offered the ammonium 3β-hydroxy-6-oxysteroid sulfateds (4a～4b) and the treatment of 4a～4b by Cation exchange resin 732 (so-dium form) gave the compounds 5a～5b. The 6a～6b were obtained by the reduction of 5a～5b using NaBH4 as reductive reagent. Using similar synthetic method, sodium 3β,6-dihydroxycholest-4-ene- 3-sulfated (10a) was obtained. The cytotoxicity of 5a～5b and 6a～6b against Hey-1B (human ovarian car-cinoma cell line) cells was investigated. The results showed that 6a had a distinct cytotoxicity (IC50: 48 nmol/mL).

Key words: sterol, sodium sterol sulfated, sodium 3,6-dihydroxysteroid-3-sulfated, synthesis