Bischler-Napieralski反应合成那可丁及其衍生物的立体化学

Stereochemistry of Narcotine and Phthalideisoquinoline Synthesized via Bischler-Napieralski Reaction

对通过Bischler-Napieralski反应制备的那可丁及其衍生物的立体选择性进行了研究.以N-β-(3-甲氧基-4,5-亚甲二氧基苯基)乙基-6',7'-二甲氧基苯并呋喃酮-3-酰胺(1)和N-β-(3,4-亚甲二氧基苯基)乙基-6',7'-二甲氧基苯并呋喃酮-3-酰胺(2)为原料,经Bischler-Napieralski反应和硼氢化钠还原制得五对苯酞类四氢异喹啉类化合物对映体3,4a,4b,5a,5b,其中3和5a经氮甲基化反应得到外消旋的那可丁(α-narcotine)和白毛莨碱(β-hydrastine).该法制得的苯酞类四氢异喹啉类化合物具有一定的立体选择性,产物构型以赤式对映体为主,中间产物二氢异喹啉环8位取代基的空间位阻将导致硼氢化钠还原时产生立体选择性.

To investigate the stereoselectivity of noscapine and its derivatives obtained via Bis- chler-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-benzodioxol- 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. （±）-a-Narcotine and （4-）-fl-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.