Acta Chimica Sinica ›› 2011, Vol. 69 ›› Issue (03): 356-361. Previous Articles    

Note

Bischler-Napieralski反应合成那可丁及其衍生物的立体化学

那路新,赵冬梅*,宋帅,孙亮,程卯生   

  1. (基于靶点的药物设计与研究教育部重点实验室 沈阳药科大学制药工程学院 沈阳 110016)
  • 收稿日期:2010-06-23 修回日期:2010-08-22 出版日期:2011-02-14 发布日期:2010-09-06
  • 通讯作者: 赵冬梅 E-mail:dongmeiz-67@163.com

Stereochemistry of Narcotine and Phthalideisoquinoline Synthesized via Bischler-Napieralski Reaction

NA Lu-Xin, ZHAO Dong-Mei, SONG Shuai, SUN Liang, CHENG Mao-Sheng   

  1. (Key Lab of Structure-Based Drugs Design and Discovery (Ministry of Education), School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016)
  • Received:2010-06-23 Revised:2010-08-22 Online:2011-02-14 Published:2010-09-06
  • Contact: Dong-Mei ZHAO E-mail:dongmeiz-67@163.com

To investigate the stereoselectivity of noscapine and its derivatives obtained via Bischler-Napieralski reaction, five pairs of phthalideisoquinoline enantiomers 3, 4a, 4b, 5a, 5b were synthesized with 1-isobenzofurancarboxamide,1,3-dihydro-4,5-dimethoxy-N-[2-(7-methoxy-1,3-benzodio xol- 5-yl)ethyl]-3-oxo- (1) and 1-isobenzofurancarboxamide,N-[2-(1,3-benzodioxol-5-yl)ethyl]-1,3-dihydro-4,5- dimethoxy-3-oxo- (2), via two process including Bischler-Napieralski reaction and reduction of sodium borohydride. (±)-α-Narcotine and (±)-β-hydrastine were prepared through N-methylation reaction from 3 and 5a. The phthalideisoquinoline synthesized via this methods has stereoselectivity. We got pairs of erythro isomers predominantly, and found small amounts of threo configuration products. The steric hindrance on 8-substituent group of intermediate products 3,4-tetrahydroisoquinoline (M) caused the stereoselectivity in the process of reduction with sodium borohydride.

Key words: narcotine, phthalideisoquinoline, Bischler-Napieralski reaction, stereoselectivity