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有机化学
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有机化学 ›› 2009, Vol. 29 ›› Issue (02): 259-264. 上一篇    下一篇

研究论文

从青藤碱制备具有(＋)-C-Normorphinan骨架的化合物

李玉峰; 卜清明; 潘 毅* ; 李建新; 黄乐群   

  1. (a南京工业大学理学院 南京 210009)
    (b南京大学化学化工学院 南京 210093)
    (c南京大学医学院 南京 210093)
  • 收稿日期:2008-04-28 修回日期:2008-08-27 发布日期:2009-02-20
  • 通讯作者: 潘 毅

Synthesis of (＋)-C-Normorphinan Analogs Starting from Sinomenine

Li, Yufeng; Bu, Qingming ; Pan, Yi*; Li, Jianxin; Huang, Lequn   

  1. (a School of Science, Nanjing University of Technology, Nanjing 210009)
    (b Department of Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093)
    (c School of Medicine, Nanjing University, Nanjing 210093)
  • Received:2008-04-28 Revised:2008-08-27 Published:2009-02-20
  • Contact: Pan, Yi

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对青藤碱进行Mitsunobu甲基化反应, 得到O-甲基青藤碱(2); 2经过酸性水解、硼氢化还原以及高碘酸钠氧化开环得到O-甲基青藤碱二醛(5); 在哌啶存在下对5进行羟醛缩合反应, 区域选择性地闭环生成具有(＋)-C-normorphinan骨架的化合物(8S,12S,13R)-6,7-didehydro-3,4-dimethoxy-16-methyl-C-normorphinan-7-carboxaldehyde (7); 经过以上五步反应, 7的总收率约35%. 对7进行硼氢化还原得到化合物8; 化合物8以醋酐进行酯化得到化合物9. 化合物7以5% Pd/C为催化剂、1.01×105 Pa下与氢气作用发生双键氢化反应, 立体定向地得到化合物10, 从化合物10出发获得化合物11和12. 通过对化合物11的1H NMR, 13C NMR, 2D-NMR及NOESY等核磁共振分析确定化合物10, 11和12具有7S绝对构型.

关键词: 青藤碱, O-甲基青藤碱二醛, (＋)-C-normorphinan化合物

Sinomenine (1) was O-methylated under Mitsunobu conditions to give O-methylsinomenine (2), which was converted into O-methylsinomeninedialdehyde (5) through a procedure of acid hydrolysis, borohydride reduction and thereafter oxidation with NaIO4. Ring-closure of 5 through Adol reaction in the presence of piperidine provided (8S,12S,13R)-6,7-didehydro-3,4-dimethoxy-16-methyl-C-normorphinan-7-
carboxaldehyde (7) with (＋)-C-normorphinan skeleton in a total yield of about 35% from sinomenine. Thereby, compound 8 was prepared by the reduction of 7. And through esterification of 8 with acetic anhy-dride, compound 9 was synthesized. The hydrogenation of 7 with 5% Pd/C as catalyst under 1.01×105 Pa of hydrogen provided compound 10 stereo-directedly. Compounds 11 and 12 were obtained starting from 10. 10, 11 and 12 were determined as of 7S configuration based on the 1H NMR, 13C NMR, 2D-NMR and NO-ESY analysis of compound 11.

Key words: O-methylsinomenine, (＋)-C-normorphinan, sinomenine