Development of a pilot scale process for the anti-Alzheimer drug (-)-galanthamine using large-scale phenolic oxidative coupling and crystallisation-induced chiral conversion

被引：103
作者：
Küenburg, B
Czollner, L
Fröhlich, J
Jordis, U
机构：
[1] Vienna Univ Technol, Inst Organ Chem, A-1060 Vienna, Austria
[2] Sanochemia AG, A-2491 Neufeld, Austria
来源：
ORGANIC PROCESS RESEARCH & DEVELOPMENT | 1999年 / 3卷 / 06期
关键词：
D O I：
10.1021/op990019q
中图分类号：
O69 [应用化学];
学科分类号：
081704 ;
摘要：
(-)-Galanthamine has been synthesised using an efficient nine-step procedure, which in large scale affords 12.4 (6.7-19.1)% overall yield. The process improvements and optimization of each step are described. Notable steps include (i) an oxidative phenol coupling and (ii) crystallisation-induced chiral conversion of (+/-)-narwedine to (-)-narwedine. This is a practical and cost-effective synthesis of (-)-galanthamine which is amenable to pilot plant scale-up to afford sufficient material for use in clinical trials.
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收藏
页码：425 / 431
页数：7
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