从青藤碱制备具有(+)-C-Normorphinan骨架的化合物  

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

作　　者：李玉峰[1] 卜清明[2] 潘毅[2] 李建新[2] 黄乐群[3] 

机构地区：[1]南京工业大学理学院,南京210009 [2]南京大学化学化工学院,南京210093 [3]南京大学医学院,南京210093

出　　处：《有机化学》2009年第2期259-264,共6页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.20772056)资助项目

摘　　要：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、1.01×105Pa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1HNMR,13CNMR,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.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 NalO4. 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 anhydride, compound 9 was synthesized. The hydrogenation of 7 with 5% Pd/C as catalyst under 1.01 × 10^5 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 NOESY analysis of compound 11.

关 键 词：青藤碱 O-甲基青藤碱二醛 (+)-C-normorphinan化合物 

分 类 号：O621.3[理学—有机化学]