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-benzodioxol-5-yl)ethyl]-3-oxo- (1) and 1-isobenzofurancarboxarnide,N-[2-(1,3-benzodioxol-5-yl)ethyl]-l,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.%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(a-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氧化钠还原时产生立体选择性.
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